A tandem regression-outlier analysis of a ligand cellular system for key structural modifications around ligand binding.

Science.gov (United States)

Lin, Ying-Ting

2013-04-30

A tandem technique of hard equipment is often used for the chemical analysis of a single cell to first isolate and then detect the wanted identities. The first part is the separation of wanted chemicals from the bulk of a cell; the second part is the actual detection of the important identities. To identify the key structural modifications around ligand binding, the present study aims to develop a counterpart of tandem technique for cheminformatics. A statistical regression and its outliers act as a computational technique for separation. A PPARγ (peroxisome proliferator-activated receptor gamma) agonist cellular system was subjected to such an investigation. Results show that this tandem regression-outlier analysis, or the prioritization of the context equations tagged with features of the outliers, is an effective regression technique of cheminformatics to detect key structural modifications, as well as their tendency of impact to ligand binding. The key structural modifications around ligand binding are effectively extracted or characterized out of cellular reactions. This is because molecular binding is the paramount factor in such ligand cellular system and key structural modifications around ligand binding are expected to create outliers. Therefore, such outliers can be captured by this tandem regression-outlier analysis.

Isotropic LQC and LQC-inspired models with a massless scalar field as generalised Brans-Dicke theories

Science.gov (United States)

Rama, S. Kalyana

2018-06-01

We explore whether generalised Brans-Dicke theories, which have a scalar field Φ and a function ω (Φ ), can be the effective actions leading to the effective equations of motion of the LQC and the LQC-inspired models, which have a massless scalar field σ and a function f( m). We find that this is possible for isotropic cosmology. We relate the pairs (σ , f) and (Φ , ω ) and, using examples, illustrate these relations. We find that near the bounce of the LQC evolutions for which f(m) = sin m, the corresponding field Φ → 0 and the function ω (Φ ) ∝ Φ ^2. We also find that the class of generalised Brans-Dicke theories, which we had found earlier to lead to non singular isotropic evolutions, may be written as an LQC-inspired model. The relations found here in the isotropic cases do not apply to the anisotropic cases, which perhaps require more general effective actions.

Quantitative analysis of protein-ligand interactions by NMR.

Science.gov (United States)

Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

2016-08-01

Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used

Singular Value Decomposition and Ligand Binding Analysis

Directory of Open Access Journals (Sweden)

André Luiz Galo

2013-01-01

Full Text Available Singular values decomposition (SVD is one of the most important computations in linear algebra because of its vast application for data analysis. It is particularly useful for resolving problems involving least-squares minimization, the determination of matrix rank, and the solution of certain problems involving Euclidean norms. Such problems arise in the spectral analysis of ligand binding to macromolecule. Here, we present a spectral data analysis method using SVD (SVD analysis and nonlinear fitting to determine the binding characteristics of intercalating drugs to DNA. This methodology reduces noise and identifies distinct spectral species similar to traditional principal component analysis as well as fitting nonlinear binding parameters. We applied SVD analysis to investigate the interaction of actinomycin D and daunomycin with native DNA. This methodology does not require prior knowledge of ligand molar extinction coefficients (free and bound, which potentially limits binding analysis. Data are acquired simply by reconstructing the experimental data and by adjusting the product of deconvoluted matrices and the matrix of model coefficients determined by the Scatchard and McGee and von Hippel equation.

Physicists get INSPIREd

CERN Multimedia

CERN Bulletin

2010-01-01

Particle physicists thrive on information. They first create information by performing experiments or elaborating theoretical conjectures and then they share it through publications and various web tools. The INSPIRE service, just released, will bring state of the art information retrieval to the fingertips of researchers.   Keeping track of the information shared within the particle physics community has long been the task of libraries at the larger labs, such as CERN, DESY, Fermilab and SLAC, as well as the focus of indispensible services like arXiv and those of the Particle Data Group. In 2007, many providers of information in the field came together for a summit at SLAC to see how physics information resources could be enhanced, and the INSPIRE project emerged from that meeting. The vision behind INSPIRE was built by a survey launched by the four labs to evaluate the real needs of the community. INSPIRE responds to these directives from the community by combining the most successful aspe...

INSPIRE: Managing Metadata in a Global Digital Library for High-Energy Physics

OpenAIRE

Martin Montull, Javier

2011-01-01

Four leading laboratories in the High-Energy Physics (HEP) field are collaborating to roll-out the next-generation scientific information portal: INSPIRE. The goal of this project is to replace the popular 40 year-old SPIRES database. INSPIRE already provides access to about 1 million records and includes services such as fulltext search, automatic keyword assignment, ingestion and automatic display of LaTeX, citation analysis, automatic author disambiguation, metadata harvesting, extraction ...

A grand unified model for liganded gold clusters

Science.gov (United States)

Xu, Wen Wu; Zhu, Beien; Zeng, Xiao Cheng; Gao, Yi

2016-12-01

A grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three `flavours' (namely, bottom, middle and top) to represent three possible valence states. The `composite particles' in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design.

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects

Science.gov (United States)

Wu, Kevin; Doyle, Abigail G.

2017-08-01

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment—cone angle and % buried volume—are not equivalent, despite their treatment in the literature.

Experimental modal analysis of fractal-inspired multi-frequency structures for piezoelectric energy converters

International Nuclear Information System (INIS)

Castagnetti, D

2012-01-01

An important issue in the field of energy harvesting through piezoelectric materials is the design of simple and efficient structures which are multi-frequency in the ambient vibration range. This paper deals with the experimental assessment of four fractal-inspired multi-frequency structures for piezoelectric energy harvesting. These structures, thin plates of square shape, were proposed in a previous work by the author and their modal response numerically analysed. The present work has two aims. First, to assess the modal response of these structures through an experimental investigation. Second, to evaluate, through computational simulation, the performance of a piezoelectric converter relying on one of these fractal-inspired structures. The four fractal-inspired structures are examined in the range between 0 and 100 Hz, with regard to both eigenfrequencies and eigenmodes. In the same frequency range, the modal response and power output of the piezoelectric converter are investigated. (paper)

Kids Inspire Kids for STEAM

OpenAIRE

Fenyvesi, Kristof; Houghton, Tony; Diego-Mantecón, José Manuel; Crilly, Elizabeth; Oldknow, Adrian; Lavicza, Zsolt; Blanco, Teresa F.

2017-01-01

Abstract The goal of the Kids Inspiring Kids in STEAM (KIKS) project was to raise students' awareness towards the multi- and transdisciplinary connections between the STEAM subjects (Science, Technology, Engineering, Arts & Mathematics), and make the learning about topics and phenomena from these fields more enjoyable. In order to achieve these goals, KIKS project has popularized the STEAM-concept by projects based on the students inspiring other students-approach and by utilizing new tec...

Effect of Ligand Field Tuning on the SMM Behavior for Three Related Alkoxide-Bridged Dysprosium Dimers.

Science.gov (United States)

Peng, Yan; Mereacre, Valeriu; Baniodeh, Amer; Lan, Yanhua; Schlageter, Martin; Kostakis, George E; Powell, Annie K

2016-01-04

The synthesis and characterization of three Dy2 compounds, [Dy2(HL1)2(NO3)4] (1), [Dy2(L2)2(NO3)4] (2), and [Dy2(HL3)2(NO3)4] (3), formed using related tripodal ligands with a central tertiary amine bearing picolyl and alkoxy arms, 2-[(2-hydroxy-ethyl)-pyridin-2-ylmethylamino]-ethanol (H2L1), 2-(bis-pyridin-2-ylmethylamino)-ethanol (HL2), and 2-(bis-pyridin-2-ylmethylamino)-propane-1,3-diol (H2L3), are reported. The compounds are rare examples of alkoxide-bridged {Dy2} complexes and display capped square antiprism coordination geometry around each Dy(III) ion. Changes in the ligand field environment around the Dy(III) ions brought about through variations in the ligand donors can be gauged from the magnetic properties, with compounds 1 and 2 showing antiparallel coupling between the Dy(III) ions and 3 showing parallel coupling. Furthermore, slow relaxation of the magnetization typical of SMM behavior could be observed for compounds 2 and 3, suggesting that small variations in the ligand field can have a significant influence on the slow relaxation processes responsible for SMM behavior of Dy(III)-based systems.

Improved approximate inspirals of test bodies into Kerr black holes

International Nuclear Information System (INIS)

Gair, Jonathan R; Glampedakis, Kostas

2006-01-01

We present an improved version of the approximate scheme for generating inspirals of test bodies into a Kerr black hole recently developed by Glampedakis, Hughes and Kennefick. Their original 'hybrid' scheme was based on combining exact relativistic expressions for the evolution of the orbital elements (the semilatus rectum p and eccentricity e) with an approximate, weak-field, formula for the energy and angular momentum fluxes, amended by the assumption of constant inclination angle ι during the inspiral. Despite the fact that the resulting inspirals were overall well behaved, certain pathologies remained for orbits in the strong-field regime and for orbits which are nearly circular and/or nearly polar. In this paper we eliminate these problems by incorporating an array of improvements in the approximate fluxes. First, we add certain corrections which ensure the correct behavior of the fluxes in the limit of vanishing eccentricity and/or 90 deg. inclination. Second, we use higher order post-Newtonian formulas, adapted for generic orbits. Third, we drop the assumption of constant inclination. Instead, we first evolve the Carter constant by means of an approximate post-Newtonian expression and subsequently extract the evolution of ι. Finally, we improve the evolution of circular orbits by using fits to the angular momentum and inclination evolution determined by Teukolsky-based calculations. As an application of our improved scheme, we provide a sample of generic Kerr inspirals which we expect to be the most accurate to date, and for the specific case of nearly circular orbits we locate the critical radius where orbits begin to decircularize under radiation reaction. These easy-to-generate inspirals should become a useful tool for exploring LISA data analysis issues and may ultimately play a role in the detection of inspiral signals in the LISA data

Communication analysis for feedback control of civil infrastructure using cochlea-inspired sensing nodes

Science.gov (United States)

Peckens, Courtney A.; Cook, Ireana; Lynch, Jerome P.

2016-04-01

Wireless sensor networks (WSNs) have emerged as a reliable, low-cost alternative to the traditional wired sensing paradigm. While such networks have made significant progress in the field of structural monitoring, significantly less development has occurred for feedback control applications. Previous work in WSNs for feedback control has highlighted many of the challenges of using this technology including latency in the wireless communication channel and computational inundation at the individual sensing nodes. This work seeks to overcome some of those challenges by drawing inspiration from the real-time sensing and control techniques employed by the biological central nervous system and in particular the mammalian cochlea. A novel bio-inspired wireless sensor node was developed that employs analog filtering techniques to perform time-frequency decomposition of a sensor signal, thus encompassing the functionality of the cochlea. The node then utilizes asynchronous sampling of the filtered signal to compress the signal prior to communication. This bio-inspired sensing architecture is extended to a feedback control application in order to overcome the traditional challenges currently faced by wireless control. In doing this, however, the network experiences high bandwidths of low-significance information exchange between nodes, resulting in some lost data. This study considers the impact of this lost data on the control capabilities of the bio-inspired control architecture and finds that it does not significantly impact the effectiveness of control.

THE COMPLEX OF EMOTIONAL EXPERIENCES, RELEVANT MANIFESTATIONS OF INSPIRATION

Directory of Open Access Journals (Sweden)

Pavel A. Starikov

2015-01-01

Full Text Available The aim of the study is to investigate structure of emotional experiences, relevant manifestations of inspiration creative activities of students.Methods. The proposed methods of mathematical statistics (correlation analysis, factor analysis, multidimensional scaling are applied.Results and scientific novelty. The use of factor analysis, multidimensional scaling allowed to reveal a consistent set of positive experiences of the students, the relevant experience of inspiration in creative activities. «Operational» rueful feelings dedicated by M. Chiksentmihaji («feeling of full involvement, and dilution in what you do», «feeling of concentration, perfect clarity of purpose, complete control and a feeling of total immersion in a job that does not require special efforts» and experiences of the «spiritual» nature, more appropriate to peaks experiences of A. Maslow («feeling of love for all existing, all life»; «a deep sense of self importance, the inner feeling of approval of self»; «feeling of unity with the whole world»; «acute perception of the beauty of the world of nature, “beautiful instant”»; «feeling of lightness, flowing» are included in this complex in accordance with the study results. The interrelation of degree of expressiveness of the given complex of experiences with inspiration experience is considered.Practical significance. The results of the study show structure of emotional experiences, relevant manifestations of inspiration. Research materials can be useful both to psychologists, and experts in the field of pedagogy of creative activity.

Inspiring a generation

CERN Multimedia

2012-01-01

The motto of the 2012 Olympic and Paralympic Games is ‘Inspire a generation’ so it was particularly pleasing to see science, the LHC and Higgs bosons featuring so strongly in the opening ceremony of the Paralympics last week.   It’s a sign of just how far our field has come that such a high-profile event featured particle physics so strongly, and we can certainly add our support to that motto. If the legacy of London 2012 is a generation inspired by science as well as sport, then the games will have more than fulfilled their mission. Particle physics has truly inspiring stories to tell, going well beyond Higgs and the LHC, and the entire community has played its part in bringing the excitement of frontier research in particle physics to a wide audience. Nevertheless, we cannot rest on our laurels: maintaining the kind of enthusiasm for science we witnessed at the Paralympic opening ceremony will require constant vigilance, and creative thinking about ways to rea...

Strong ligand field effects of blue phosphorescent mono-cyclometalated iridium(III) complexes

International Nuclear Information System (INIS)

Ham, Ho Wan; Jung, Kyung Yoon; Kim, Young Sik

2010-01-01

A series of mono-cyclometalated blue phosphorescent iridium(III) complexes with two phosphines trans to each other and two cis-ancillary ligands, such as Ir(F 2 Meppy)(PPhMe 2 ) 2 (H)(Cl), [Ir(F 2 Meppy)(PPhMe 2 ) 2 (H)(NCMe)] + and Ir(F 2 Meppy)(PPhMe 2 ) 2 -(H)(CN), [F 2 Meppy = 2-(2',4'-difluorophenyl)-4-methyl-pyridine] were synthesized and studied to tune the phosphorescence wavelength to the deep blue region and to enhance the luminescence efficiencies. We investigate the electron-withdrawing capabilities of ancillary ligands using the DFT and TD-DFT calculations on the ground and excited states of the three complexes to gain insight into the factors responsible for the emission color change and the different luminescence efficiency. Reducing the molecular weight of phosphine ligand with PPhMe 2 leads to a strategy of the efficient deep blue organic light-emitting devices (OLED) by thermal processing instead of the solution processing. The electron-withdrawing difluoro group substituted on the phenyl ring and the cyano strong field ancillary ligand in the trans position to the carbon atom of phenyl ring increased HOMO-LUMO gap and achieved the hypsochromic shift in emission color. As a result, the maximum emission spectra of Ir(F 2 Meppy)(PPhMe 2 ) 2 (H)(Cl), [Ir(F 2 Meppy)(PPhMe 2 ) 2 (H)-(NCMe)] + and Ir(F 2 Meppy)(PPh-Me 2 ) 2 (H)(CN) were in the ranges of 446, 440, 439 nm, respectively.

A survey of snake-inspired robot designs

International Nuclear Information System (INIS)

Hopkins, James K; Spranklin, Brent W; Gupta, Satyandra K

2009-01-01

Body undulation used by snakes and the physical architecture of a snake body may offer significant benefits over typical legged or wheeled locomotion designs in certain types of scenarios. A large number of research groups have developed snake-inspired robots to exploit these benefits. The purpose of this review is to report different types of snake-inspired robot designs and categorize them based on their main characteristics. For each category, we discuss their relative advantages and disadvantages. This review will assist in familiarizing a newcomer to the field with the existing designs and their distinguishing features. We hope that by studying existing robots, future designers will be able to create new designs by adopting features from successful robots. The review also summarizes the design challenges associated with the further advancement of the field and deploying snake-inspired robots in practice. (topical review)

Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

Science.gov (United States)

Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

1995-01-01

A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

Exploring Creativity in the Bio-Inspired Design Process

DEFF Research Database (Denmark)

Anggakara, K.; Aksdal, T.; Onarheim, Balder

2015-01-01

The growing interest in the of field bio-inspired design has been driven by the acknowledgement that inspiration from nature can serve as a valuable source of innovation. As an emerging approach, there has been a focus on building a principled methodology to address the challenges that arise...

Nature-inspired optimization algorithms

CERN Document Server

Yang, Xin-She

2014-01-01

Nature-Inspired Optimization Algorithms provides a systematic introduction to all major nature-inspired algorithms for optimization. The book's unified approach, balancing algorithm introduction, theoretical background and practical implementation, complements extensive literature with well-chosen case studies to illustrate how these algorithms work. Topics include particle swarm optimization, ant and bee algorithms, simulated annealing, cuckoo search, firefly algorithm, bat algorithm, flower algorithm, harmony search, algorithm analysis, constraint handling, hybrid methods, parameter tuning

Ligand field and intermolecular interactions tuning the magnetic properties of spin-crossover Fe(II) polymer with 4,4′-bipyridine

Energy Technology Data Exchange (ETDEWEB)

Luo, Yang-Hui; Liu, Qing-Ling; Yang, Li-Jing; Ling, Yang; Wang, Wei; Sun, Bai-Wang, E-mail: chmsunbw@seu.edu.cn

2015-02-15

A new spin crossover coordination polymer (SCO-CPs) of Fe(II)-4,4′-bipyridine (4,4′-bipy) family: (Fe(4,4′-bipy){sub 2}(H{sub 2}O){sub 2})·(4,4′-bipy)· 8(H{sub 2}O)·2(ClO{sub 4}) (3), which displays half spin transitions between 100 and 300 K, has been synthesized and structurally characterized. Compound 3 featured with two-dimensional (2-D) grids connected by hydrogen bonds and π…π packing between one-dimensional (1-D) chains, the 2-D grids expand to three-dimensional (3-D) architecture supported by a “S-shaped holder” involving lattice 4-4′-bipy, water molecules and perchlorate anion. We compared 3 with the other two analogous complexes: ((Fe(4,4′-bipy) (H{sub 2}O){sub 2} (NCS){sub 2})·4,4′-bipy, 1 and (Fe(4,4′-bipy){sub 2}(NCS){sub 2})·mSolv, 2) through Hirshfeld surfaces analysis, which revealed that the low ligand field strength (NCS{sup −}) and lone-pair…H contacts contribute to the stabilization of HS (high-spin) state of the Fe(II) ion, while the high ligand field strength (4,4′-bipy) and strong intermolecular contacts (hydrogen bonds and π…π packing interactions) make for the LS (low-spin) state. - Highlights: ●A new member of Fe(||)-4,4′-bipy family has been prepared. ●It displays half spin transitions tuned by ligand field and intermolecular interactions. ●We have made a detailed comparison of this new member with two other analogous complexes.

Strong ligand field effects of blue phosphorescent mono-cyclometalated iridium(III) complexes

Energy Technology Data Exchange (ETDEWEB)

Ham, Ho Wan [Department of Information Display, Hongik University, Seoul, 121-791 (Korea, Republic of); Jung, Kyung Yoon [International Design School for Advanced Studies, Hongik University, Seoul 121-791 (Korea, Republic of); Kim, Young Sik, E-mail: youngkim@hongik.ac.k [Department of Information Display, Hongik University, Seoul, 121-791 (Korea, Republic of)

2010-09-01

A series of mono-cyclometalated blue phosphorescent iridium(III) complexes with two phosphines trans to each other and two cis-ancillary ligands, such as Ir(F{sub 2}Meppy)(PPhMe{sub 2}){sub 2}(H)(Cl), [Ir(F{sub 2}Meppy)(PPhMe{sub 2}){sub 2}(H)(NCMe)]{sup +} and Ir(F{sub 2}Meppy)(PPhMe{sub 2}){sub 2}-(H)(CN), [F{sub 2}Meppy = 2-(2',4'-difluorophenyl)-4-methyl-pyridine] were synthesized and studied to tune the phosphorescence wavelength to the deep blue region and to enhance the luminescence efficiencies. We investigate the electron-withdrawing capabilities of ancillary ligands using the DFT and TD-DFT calculations on the ground and excited states of the three complexes to gain insight into the factors responsible for the emission color change and the different luminescence efficiency. Reducing the molecular weight of phosphine ligand with PPhMe{sub 2} leads to a strategy of the efficient deep blue organic light-emitting devices (OLED) by thermal processing instead of the solution processing. The electron-withdrawing difluoro group substituted on the phenyl ring and the cyano strong field ancillary ligand in the trans position to the carbon atom of phenyl ring increased HOMO-LUMO gap and achieved the hypsochromic shift in emission color. As a result, the maximum emission spectra of Ir(F{sub 2}Meppy)(PPhMe{sub 2}){sub 2}(H)(Cl), [Ir(F{sub 2}Meppy)(PPhMe{sub 2}){sub 2}(H)-(NCMe)]{sup +} and Ir(F{sub 2}Meppy)(PPh-Me{sub 2}){sub 2} (H)(CN) were in the ranges of 446, 440, 439 nm, respectively.

Toward Improved Force-Field Accuracy through Sensitivity Analysis of Host-Guest Binding Thermodynamics

Science.gov (United States)

Yin, Jian; Fenley, Andrew T.; Henriksen, Niel M.; Gilson, Michael K.

2015-01-01

Improving the capability of atomistic computer models to predict the thermodynamics of noncovalent binding is critical for successful structure-based drug design, and the accuracy of such calculations remains limited by non-optimal force field parameters. Ideally, one would incorporate protein-ligand affinity data into force field parametrization, but this would be inefficient and costly. We now demonstrate that sensitivity analysis can be used to efficiently tune Lennard-Jones parameters of aqueous host-guest systems for increasingly accurate calculations of binding enthalpy. These results highlight the promise of a comprehensive use of calorimetric host-guest binding data, along with existing validation data sets, to improve force field parameters for the simulation of noncovalent binding, with the ultimate goal of making protein-ligand modeling more accurate and hence speeding drug discovery. PMID:26181208

Geo-inspired model: Agents vectors naturals inspired by the environmental management (AVNG of water tributaries

Directory of Open Access Journals (Sweden)

Edwin Eduardo Millán Rojas

2018-02-01

Full Text Available Context: Management to care for the environment and the Earth (geo can be source of inspiration for developing models that allow addressing complexity issues; the objective of this research was to develop an additional aspect of the inspired models. The geoinspired model has two features, the first covering aspects related to environmental management and the behavior of natural resources, and the second has a component of spatial location associated with existing objects on the Earth's surface. Method: The approach developed in the research is descriptive and its main objective is the representation or characterization of a case study within a particular context. Results: The result was the design of a model to emulate the natural behavior of the water tributaries of the Amazon foothills, in order to extend the application of the inspired models and allow the use of elements such as geo-referencing and environmental management. The proposed geoinspired model is called “natural vectors agents inspired in environmental management”. Conclusions: The agents vectors naturals inspired by the environmental are polyform elements that can assume the behavior of environmental entities, which makes it possible to achieve progress in other fields of environmental management (use of soil, climate, flora, fauna, and link environmental issues with the structure of the proposed model.

Crickets as bio-inspiration for MEMS-based flow-sensing

NARCIS (Netherlands)

Krijnen, Gijsbertus J.M.; Droogendijk, H.; Dagamseh, A.M.K.; Jaganatharaja, R.K.; Casas, Jerome

2014-01-01

MEMS offers exciting possibilities for the fabrication of bio-inspired mechanosensors. Over the last few years, we have been working on cricket- inspired hair-sensor arrays for spatio-temporal flow-field observations (i.e. flow camera) and source localisation. Whereas making flow-sensors as energy

Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP)

Science.gov (United States)

Snyder, David A.; Chantova, Mihaela; Chaudhry, Saadia

2015-06-01

NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase.

Writing Inspired

Science.gov (United States)

Tischhauser, Karen

2015-01-01

Students need inspiration to write. Assigning is not teaching. In order to inspire students to write fiction worth reading, teachers must take them through the process of writing. Physical objects inspire good writing with depth. In this article, the reader will be taken through the process of inspiring young writers through the use of boxes.…

Bio-Inspired Design and Kinematic Analysis of Dung Beetle-Like Legs

DEFF Research Database (Denmark)

Aditya, Sai Krishna Venkata; Ignasov, Jevgeni; Filonenko, Konstantin

2017-01-01

The African dung beetle Scarabaeus galenus can use its front legs to walk and manipulate or form a dung ball. The interesting multifunctional legs have not been fully investigated or even used as inspiration for robot leg design. Thus, in this paper, we present the development of real dung beetle......-like front legs based on biological investigation. As a result, each leg consists of three main segments which were built using 3D printing. The segments were combined with in total four active DOFs in order to mimic locomotion and object manipulation of the beetle. Kinematics analysis of the leg was also...... performed to identify its workspace as well as to design its trajectory. To this end, the study contributes not only novel multifunctional robotic legs but also the methodology of the bio-inspired leg design....

Bio-inspired computation in unmanned aerial vehicles

CERN Document Server

Duan, Haibin

2014-01-01

Bio-inspired Computation in Unmanned Aerial Vehicles focuses on the aspects of path planning, formation control, heterogeneous cooperative control and vision-based surveillance and navigation in Unmanned Aerial Vehicles (UAVs) from the perspective of bio-inspired computation. It helps readers to gain a comprehensive understanding of control-related problems in UAVs, presenting the latest advances in bio-inspired computation. By combining bio-inspired computation and UAV control problems, key questions are explored in depth, and each piece is content-rich while remaining accessible. With abundant illustrations of simulation work, this book links theory, algorithms and implementation procedures, demonstrating the simulation results with graphics that are intuitive without sacrificing academic rigor. Further, it pays due attention to both the conceptual framework and the implementation procedures. The book offers a valuable resource for scientists, researchers and graduate students in the field of Control, Aeros...

Prediction of ligand effects in platinum-amyloid-β coordination.

Science.gov (United States)

Turner, Matthew; Deeth, Robert J; Platts, James A

2017-08-01

Ligand field molecular mechanics (LFMM) and semi-empirical Parametric Model 7 (PM7) methods are applied to a series of six Pt II -Ligand systems binding to the N-terminal domain of the amyloid-β (Aβ) peptide. Molecular dynamics using a combined LFMM/Assisted Model Building with Energy Refinement (AMBER) approach is used to explore the conformational freedom of the peptide fragment, and identifies favourable platinum binding modes and peptide conformations for each ligand investigated. Platinum coordination is found to depend on the nature of the ligand, providing evidence that binding mode may be controlled by suitable ligand design. Boltzmann populations at 310K indicate that each Pt-Aβ complex has a small number of thermodynamically accessible states. Ramachandran maps are constructed for the sampled Pt-Aβ conformations and secondary structural analysis of the obtained complex structures is performed and contrasted with the free peptide; coordination of these platinum complexes disrupts existing secondary structure in the Aβ peptide and promotes formation of ligand-specific turn-type secondary structure. Copyright © 2017 Elsevier Inc. All rights reserved.

Creative design inspired by biological knowledge: Technologies and methods

Science.gov (United States)

Tan, Runhua; Liu, Wei; Cao, Guozhong; Shi, Yuan

2018-05-01

Biological knowledge is becoming an important source of inspiration for developing creative solutions to engineering design problems and even has a huge potential in formulating ideas that can help firms compete successfully in a dynamic market. To identify the technologies and methods that can facilitate the development of biologically inspired creative designs, this research briefly reviews the existing biological-knowledge-based theories and methods and examines the application of biological-knowledge-inspired designs in various fields. Afterward, this research thoroughly examines the four dimensions of key technologies that underlie the biologically inspired design (BID) process. This research then discusses the future development trends of the BID process before presenting the conclusions.

Combining Bio-inspired Sensing with Bio-inspired Locomotion

DEFF Research Database (Denmark)

Shaikh, Danish; Hallam, John; Christensen-Dalsgaard, Jakob

In this paper we present a preliminary Braitenberg vehicle–like approach to combine bio-inspired audition with bio-inspired quadruped locomotion in simulation. Locomotion gaits of the salamander–like robot Salamandra robotica are modified by a lizard’s peripheral auditory system model that modula......In this paper we present a preliminary Braitenberg vehicle–like approach to combine bio-inspired audition with bio-inspired quadruped locomotion in simulation. Locomotion gaits of the salamander–like robot Salamandra robotica are modified by a lizard’s peripheral auditory system model...

Ligand field theory and the origin of life as an emergent feature of the periodic table of elements.

Science.gov (United States)

Morowitz, Harold J; Srinivasan, Vijayasarathy; Smith, Eric

2010-08-01

The assumption that all biological catalysts are either proteins or ribozymes leads to an outstanding enigma of biogenesis-how to determine the synthetic pathways to the monomers for the efficient formation of catalytic macromolecules in the absence of any such macromolecules. The last 60 years have witnessed chemists developing an understanding of organocatalysis and ligand field theory, both of which give demonstrable low-molecular-weight catalysts. We assume that transition-metal-ligand complexes are likely to have occurred in the deep ocean trenches by the combination of naturally occurring oceanic metals and ligands synthesized from the emergent CO(2), H(2), NH(3), H(2)S, and H(3)PO(4). We are now in a position to investigate experimentally the metal-ligand complexes, their catalytic function, and the reaction networks that could have played a role in the development of metabolism and life itself.

Neuroscience-Inspired Artificial Intelligence.

Science.gov (United States)

Hassabis, Demis; Kumaran, Dharshan; Summerfield, Christopher; Botvinick, Matthew

2017-07-19

The fields of neuroscience and artificial intelligence (AI) have a long and intertwined history. In more recent times, however, communication and collaboration between the two fields has become less commonplace. In this article, we argue that better understanding biological brains could play a vital role in building intelligent machines. We survey historical interactions between the AI and neuroscience fields and emphasize current advances in AI that have been inspired by the study of neural computation in humans and other animals. We conclude by highlighting shared themes that may be key for advancing future research in both fields. Copyright © 2017. Published by Elsevier Inc.

Strong ligand field effects of blue phosphorescent Ir(III) complexes with phenylpyrazole and phosphines.

Science.gov (United States)

Park, Se Won; Ham, Ho Wan; Kim, Young Sik

2012-04-01

In the paper, we describe new Ir complexes for achieving efficient blue phosphorescence. New blue-emitting mixed-ligand Ir complexes comprising one cyclometalating, two phosphines trans to each other such as Ir(dppz)(PPh3)2(H)(L) (Ll= Cl, NCMe+, CN), [dppz = 3,5-Diphenylpyrazole] were synthesized and studied to tune the phosphorescence wavelength to the deep blue region and to enhance the luminescence efficiencies. To gain insight into the factors responsible for the emission color change and the variation of luminescence efficiency, we investigate the electron-withdrawing capabilities of ancillary ligands using DFT and TD-DFT calculations on the ground and excited states of the complexes. To achieve deep blue emission and increase the emission efficiency, (1) we substitute the phenyl group on the 3-position of the pyrazole ring that lowers the triplet energy enough that the quenching channel is not thermally accessible and (2) change the ancillary ligands coordinated to iridium atom to phosphine and cyano groups known as very strong field ligands. Their inclusion in the coordination sphere can increase the HOMO-LUMO gap to achieve the hypsochromic shift in emission color and lower the HOMO and LUMO energy level, which causes a large d-orbital energy splitting and avoids the quenching effect to improve the luminescence efficiency. The maximum emission spectra of Ir(dppz)(PPh3)2(H)(CI) and Ir(dppz)(PPh3)2(H)(CN) were in the ranges of 439, 432 nm, respectively.

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng

2014-12-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng; Zheng, Bin; Huang, Kuo-Wei

2014-01-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

Directory of Open Access Journals (Sweden)

Shinichiro Fuse

2013-11-01

Full Text Available Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers.

Product and technology innovation: what can biomimicry inspire?

Science.gov (United States)

Lurie-Luke, Elena

2014-12-01

Biomimicry (bio- meaning life in Greek, and -mimesis, meaning to copy) is a growing field that seeks to interpolate natural biological mechanisms and structures into a wide range of applications. The rise of interest in biomimicry in recent years has provided a fertile ground for innovation. This review provides an eco-system based analysis of biomimicry inspired technology and product innovation. A multi-disciplinary framework has been developed to accomplish this analysis and the findings focus on the areas that have been most strikingly affected by the application of biomimicry and also highlight the emerging trends and opportunity areas. Copyright © 2014 Elsevier Inc. All rights reserved.

MULTIDENTATE TEREPHTHALAMIDATE AND HYDROXYPYRIDONATE LIGANDS: TOWARDS NEW ORALLY ACTIVE CHELATORS

Energy Technology Data Exchange (ETDEWEB)

Abergel, Rebecca J.; Raymond, Kenneth N.

2011-07-13

The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

INSPIRE: Realizing the dream of a global digital library in High-Energy Physics

CERN Document Server

Holtkamp, Annette; Simko, Tibor; Smith, Tim

2010-01-01

High-Energy Physics (HEP) has a long tradition in pioneering infrastructures for scholarly communication, and four leading laboratories are now rolling-out the next-generation digital library for the field: INSPIRE. This is an evolution of the extraordinarily successful, 40-years old SPIRES database. Based on the Invenio software, INSPIRE already provides seamless access to almost 1 million records, which will be expanded to cover multimedia, data, software, wikis. Services offered include citation analysis, fulltext search, extraction of figures from fulltext and search in figure captions, automatic keyword assignment, metadata harvesting, retrodigitization, ingestion and automatic display of LaTeX, and storage of supplementary materials like Mathematica notebooks. New services are in different phases of design or implementation, in strategic partnerships with all other information providers in the field and neighbouring disciplines, including automatic author disambiguation, user tagging, crowdsourcing of m...

Increased precision for analysis of protein-ligand dissociation constants determined from chemical shift titrations

Energy Technology Data Exchange (ETDEWEB)

Markin, Craig J.; Spyracopoulos, Leo, E-mail: leo.spyracopoulos@ualberta.ca [University of Alberta, Department of Biochemistry (Canada)

2012-06-15

NMR is ideally suited for the analysis of protein-protein and protein ligand interactions with dissociation constants ranging from {approx}2 {mu}M to {approx}1 mM, and with kinetics in the fast exchange regime on the NMR timescale. For the determination of dissociation constants (K{sub D}) of 1:1 protein-protein or protein-ligand interactions using NMR, the protein and ligand concentrations must necessarily be similar in magnitude to the K{sub D}, and nonlinear least squares analysis of chemical shift changes as a function of ligand concentration is employed to determine estimates for the parameters K{sub D} and the maximum chemical shift change ({Delta}{delta}{sub max}). During a typical NMR titration, the initial protein concentration, [P{sub 0}], is held nearly constant. For this condition, to determine the most accurate parameters for K{sub D} and {Delta}{delta}{sub max} from nonlinear least squares analyses requires initial protein concentrations that are {approx}0.5 Multiplication-Sign K{sub D}, and a maximum concentration for the ligand, or titrant, of {approx}10 Multiplication-Sign [P{sub 0}]. From a practical standpoint, these requirements are often difficult to achieve. Using Monte Carlo simulations, we demonstrate that co-variation of the ligand and protein concentrations during a titration leads to an increase in the precision of the fitted K{sub D} and {Delta}{delta}{sub max} values when [P{sub 0}] > K{sub D}. Importantly, judicious choice of protein and ligand concentrations for a given NMR titration, combined with nonlinear least squares analyses using two independent variables (ligand and protein concentrations) and two parameters (K{sub D} and {Delta}{delta}{sub max}) is a straightforward approach to increasing the accuracy of measured dissociation constants for 1:1 protein-ligand interactions.

Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

Directory of Open Access Journals (Sweden)

Tino Wolter

Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

Inspired Responses

Science.gov (United States)

Steele, Carol Frederick

2011-01-01

In terms of teacher quality, Steele believes the best teachers have reached a stage she terms inspired, and that teachers move progressively through the stages of unaware, aware, and capable until the most reflective teachers finally reach the inspired level. Inspired teachers have a wide repertoire of teaching and class management techniques and…

INSPIRE: A new scientific information system for HEP

International Nuclear Information System (INIS)

Ivanov, R; Raae, L

2010-01-01

The status of high-energy physics (HEP) information systems has been jointly analyzed by the libraries of CERN, DESY, Fermilab and SLAC. As a result, the four laboratories have started the INSPIRE project - a new platform built by moving the successful SPIRES features and content, curated at DESY, Fermilab and SLAC, into the open-source CDS Invenio digital library software that was developed at CERN. INSPIRE will integrate current acquisition workflows and databases to host the entire body of the HEP literature (about one million records), aiming to become the reference HEP scientific information platform worldwide. It will provide users with fast access to full text journal articles and preprints, but also material such as conference slides and multimedia. INSPIRE will empower scientists with new tools to discover and access the results most relevant to their research, enable novel text- and data-mining applications, and deploy new metrics to assess the impact of articles and authors. In addition, it will introduce the 'Web 2.0' paradigm of user-enriched content in the domain of sciences, with community-based approaches to scientific publishing. INSPIRE represents a natural evolution of scholarly communication built on successful community-based information systems, and it provides a vision for information management in other fields of science. Inspired by the needs of HEP, we hope that the INSPIRE project will be inspiring for other communities.

A smart magnetic nanoplatform for synergistic anticancer therapy: manoeuvring mussel-inspired functional magnetic nanoparticles for pH responsive anticancer drug delivery and hyperthermia

Science.gov (United States)

Sasikala, Arathyram Ramachandra Kurup; Ghavaminejad, Amin; Unnithan, Afeesh Rajan; Thomas, Reju George; Moon, Myeongju; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

2015-10-01

We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic anticancer treatment. The unique multiple anchoring groups can be used to substantially improve the affinity of the ligands to the surfaces of the nanoparticles to form ultrastable iron oxide nanoparticles with control over their hydrodynamic diameter and interfacial chemistry. Thus the BTZ-incorporated-bio-inspired-smart magnetic nanoplatform will act as a hyperthermic agent that delivers heat when an alternating magnetic field is applied while the BTZ-bound catechol moieties act as chemotherapeutic agents in a cancer environment by providing pH-dependent drug release for the synergistic thermo-chemotherapy application. The anticancer efficacy of these bio-inspired multifunctional smart magnetic nanoparticles was tested both in vitro and in vivo and found that these unique magnetic nanoplatforms can be established to endow for the next generation of nanomedicine for efficient and safe cancer therapy.We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic

INSPIRE: Managing Metadata in a Global Digital Library for High-Energy Physics

CERN Document Server

Martin Montull, Javier

2011-01-01

Four leading laboratories in the High-Energy Physics (HEP) field are collaborating to roll-out the next-generation scientific information portal: INSPIRE. The goal of this project is to replace the popular 40 year-old SPIRES database. INSPIRE already provides access to about 1 million records and includes services such as fulltext search, automatic keyword assignment, ingestion and automatic display of LaTeX, citation analysis, automatic author disambiguation, metadata harvesting, extraction of figures from fulltext and search in figure captions. In order to achieve high quality metadata both automatic processing and manual curation are needed. The different tools available in the system use modern web technologies to provide the curators of the maximum efficiency, while dealing with the MARC standard format. The project is under heavy development in order to provide new features including semantic analysis, crowdsourcing of metadata curation, user tagging, recommender systems, integration of OAIS standards a...

[Supercomputer investigation of the protein-ligand system low-energy minima].

Science.gov (United States)

Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

2015-01-01

The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

Dynamic ligand-based pharmacophore modeling and virtual ...

Indian Academy of Sciences (India)

Five ligand-based pharmacophore models were generated from 40 different .... the Phase module of the Schrodinger program.35 Each model consisted of six types of ... ligand preparation included the OPLS_2005 force field and to retain the ...

Ab Initio Ligand Field Molecular Mechanics and the Nature of Metal-Ligand π-Bonding in Fe(II) 2,6-di(pyrazol-1-yl)pyridine Spin Crossover Complexes.

Science.gov (United States)

Deeth, Robert J; Halcrow, Malcolm A; Kershaw Cook, Laurence J; Raithby, Paul R

2018-04-06

A ligand field molecular mechanics (LFMM) force field has been constructed for the spin states of [Fe(bpp) 2 ] 2+ (bpp=2,6-di(pyrazol-1-yl)pyridine) and related complexes. A new charge scheme is employed which interpolates between partial charges for neutral bpp and protonated [H 3 bpp] 3+ to achieve a target metal charge. The LFMM angular overlap model (AOM) parameters are fitted to fully ab initio d orbital energies. However, several AOM parameter sets are possible. The ambiguity is resolved by calculating the Jahn-Teller distortion mode for high spin, which indicates that in [Fe(bpp) 2 ] 2+ pyridine is a π-acceptor and pyrazole a weak π-donor. The alternative fit, assumed previously, where both ligands act as π-donors leads to an inconsistent distortion. LFMM optimisations in the presence of [BF 4 ] - or [PF 6 ] - anions are in good agreement with experiment and the model also correctly predicts the spin state energetics for 3-pyrazolyl substituents where the interactions are mainly steric. However, for 4-pyridyl or 4-pyrazolyl substituents, LFMM only treats the electrostatic contribution which, for the pyridyl substituents, generates a fair correlation with the spin crossover transition temperatures, T 1/2 , but in the reverse sense to the dominant electronic effect. Thus, LFMM generates its smallest spin state energy difference for the substituent with the highest T 1/2 . One parameter set for all substituted bpp ligands is insufficient and further LFMM development will be required. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combining Stochastic Deformation/Relaxation and Intermolecular Contacts Analysis for Extracting Pharmacophores from Ligand-Receptor Complexes.

Science.gov (United States)

Hatmal, Ma'mon M; Taha, Mutasem O

2018-04-23

We previously combined molecular dynamics (classical or simulated annealing) with ligand-receptor contacts analysis as a means to extract valid pharmacophore model(s) from single ligand-receptor complexes. However, molecular dynamics methods are computationally expensive and time-consuming. Here we describe a novel method for extracting valid pharmacophore model(s) from a single crystallographic structure within a reasonable time scale. The new method is based on ligand-receptor contacts analysis following energy relaxation of a predetermined set of randomly deformed complexes generated from the targeted crystallographic structure. Ligand-receptor contacts maintained across many deformed/relaxed structures are assumed to be critical and used to guide pharmacophore development. This methodology was implemented to develop valid pharmacophore models for PI3K-γ, RENIN, and JAK1. The resulting pharmacophore models were validated by receiver operating characteristic (ROC) analysis against inhibitors extracted from the CHEMBL database. Additionally, we implemented pharmacophores extracted from PI3K-γ to search for new inhibitors from the National Cancer Institute list of compounds. The process culminated in new PI3K-γ/mTOR inhibitory leads of low micromolar IC 50 s.

Retina-Inspired Filter.

Science.gov (United States)

Doutsi, Effrosyni; Fillatre, Lionel; Antonini, Marc; Gaulmin, Julien

2018-07-01

This paper introduces a novel filter, which is inspired by the human retina. The human retina consists of three different layers: the Outer Plexiform Layer (OPL), the inner plexiform layer, and the ganglionic layer. Our inspiration is the linear transform which takes place in the OPL and has been mathematically described by the neuroscientific model "virtual retina." This model is the cornerstone to derive the non-separable spatio-temporal OPL retina-inspired filter, briefly renamed retina-inspired filter, studied in this paper. This filter is connected to the dynamic behavior of the retina, which enables the retina to increase the sharpness of the visual stimulus during filtering before its transmission to the brain. We establish that this retina-inspired transform forms a group of spatio-temporal Weighted Difference of Gaussian (WDoG) filters when it is applied to a still image visible for a given time. We analyze the spatial frequency bandwidth of the retina-inspired filter with respect to time. It is shown that the WDoG spectrum varies from a lowpass filter to a bandpass filter. Therefore, while time increases, the retina-inspired filter enables to extract different kinds of information from the input image. Finally, we discuss the benefits of using the retina-inspired filter in image processing applications such as edge detection and compression.

Analysis of free geo-server software usability from the viewpoint of INSPIRE requirementsAnalysis of free geo-server software usability from the viewpoint of INSPIRE requirements

Directory of Open Access Journals (Sweden)

Tomasz  Grasza

2014-06-01

Full Text Available The paper presents selected server platforms based on free and open source license, coherent with the standards of the Open Geospatial Consortium. The presented programs are evaluated in the context of the INSPIRE Directive. The first part describes the requirements of the Directive, and afterwards presented are the pros and cons of each platform, to meet these demands. This article provides an answer to the question whether the use of free software can provide interoperable network services in accordance with the requirements of the INSPIRE Directive, on the occasion of presenting the application examples and practical tips on the use of particular programs.[b]Keywords[/b]: GIS, INSPIRE, free software, OGC, geoportal, network services, GeoServer, deegree, GeoNetwork

In Search of Scientific Inspiration.

Science.gov (United States)

2017-01-12

In the ever-expanding sea of scientific advances, how do you find inspiration for your own study? Cell editor Jiaying Tan talked with Mark Lemmon and Joseph (Yossi) Schlessinger about the importance of fueling your research creativity with the conceptual excitement and technical advance from the broad scientific field. An excerpt of the conversation appears below. Copyright © 2017. Published by Elsevier Inc.

Application of 3D-QSAR in the rational design of receptor ligands and enzyme inhibitors.

Science.gov (United States)

Mor, Marco; Rivara, Silvia; Lodola, Alessio; Lorenzi, Simone; Bordi, Fabrizio; Plazzi, Pier Vincenzo; Spadoni, Gilberto; Bedini, Annalida; Duranti, Andrea; Tontini, Andrea; Tarzia, Giorgio

2005-11-01

Quantitative structure-activity relationships (QSARs) are frequently employed in medicinal chemistry projects, both to rationalize structure-activity relationships (SAR) for known series of compounds and to help in the design of innovative structures endowed with desired pharmacological actions. As a difference from the so-called structure-based drug design tools, they do not require the knowledge of the biological target structure, but are based on the comparison of drug structural features, thus being defined ligand-based drug design tools. In the 3D-QSAR approach, structural descriptors are calculated from molecular models of the ligands, as interaction fields within a three-dimensional (3D) lattice of points surrounding the ligand structure. These descriptors are collected in a large X matrix, which is submitted to multivariate analysis to look for correlations with biological activity. Like for other QSARs, the reliability and usefulness of the correlation models depends on the validity of the assumptions and on the quality of the data. A careful selection of compounds and pharmacological data can improve the application of 3D-QSAR analysis in drug design. Some examples of the application of CoMFA and CoMSIA approaches to the SAR study and design of receptor or enzyme ligands is described, pointing the attention to the fields of melatonin receptor ligands and FAAH inhibitors.

Field-effect measurements of mobility and carrier concentration of Cu2S colloidal quantum dot thin films after ligand exchange

International Nuclear Information System (INIS)

Brewer, Adam S.; Arnold, Michael S.

2014-01-01

Colloidal quantum dots (CQDs) of copper sulfide (Cu 2 S), an earth-abundant semiconductor, have a number of intriguing applications that require knowledge of their electrical properties. Depending on stoichiometry, mobility, and surface treatment, applications include photoabsorbers for solar cells, tunable plasmonics, and counter-electrodes for polysulfate electrolytes. However, there have not been any direct measurements of electrical properties in Cu 2 S CQD thin films. Here, we exchange as synthesized dodecanethiol ligands with short ethanedithiol or ethylenediamine ligands to form thin films of coupled Cu 2 S CQDs. The mobility and carrier concentration were found to vary by ligand treatment from 10 −5 cm 2 /Vs and 10 19 holes/cm 3 for ethanedithiol ligands to 10 −3 cm 2 /Vs and 10 20 holes/cm 3 for ethylenediamine. These results are consistent with the carrier concentrations inferred from sub-bandgap surface-plasmon-resonances measured by infrared spectroscopy. These results will be useful when designing Cu 2 S materials for future applications. - Highlights: • Colloidal Cu2S quantum dots were synthesized and characterized. • Ligand exchange was performed to alter the Cu2S nanocrystal properties. • Ligand exchange was studied using photoluminescence and infrared spectroscopy. • Field effect mobility and carrier concentration were directly measured. • Carrier concentration was compared to estimates from surface plasmon resonances

Rational Ligand Design for U(VI) and Pu(IV)

International Nuclear Information System (INIS)

Szigethy, Geza

2009-01-01

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO 2 2+ ). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative saturation, these

Rational Ligand Design for U(VI) and Pu(IV)

Energy Technology Data Exchange (ETDEWEB)

Szigethy, Geza [Univ. of California, Berkeley, CA (United States)

2009-08-12

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO₂ ²⁺). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative

Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties.

Science.gov (United States)

Fanali, Gabriella; Ascenzi, Paolo; Bernardi, Giorgio; Fasano, Mauro

2012-01-01

Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.

Accelerating Inspire

CERN Document Server

AUTHOR|(CDS)2266999

2017-01-01

CERN has been involved in the dissemination of scientific results since its early days and has continuously updated the distribution channels. Currently, Inspire hosts catalogues of articles, authors, institutions, conferences, jobs, experiments, journals and more. Successful orientation among this amount of data requires comprehensive linking between the content. Inspire has lacked a system for linking experiments and articles together based on which accelerator they were conducted at. The purpose of this project has been to create such a system. Records for 156 accelerators were created and all 2913 experiments on Inspire were given corresponding MARC tags. Records of 18404 accelerator physics related bibliographic entries were also tagged with corresponding accelerator tags. Finally, as a part of the endeavour to broaden CERN's presence on Wikipedia, existing Wikipedia articles of accelerators were updated with short descriptions and links to Inspire. In total, 86 Wikipedia articles were updated. This repo...

Physicists Get INSPIREd: INSPIRE Project and Grid Applications

International Nuclear Information System (INIS)

Klem, Jukka; Iwaszkiewicz, Jan

2011-01-01

INSPIRE is the new high-energy physics scientific information system developed by CERN, DESY, Fermilab and SLAC. INSPIRE combines the curated and trusted contents of SPIRES database with Invenio digital library technology. INSPIRE contains the entire HEP literature with about one million records and in addition to becoming the reference HEP scientific information platform, it aims to provide new kinds of data mining services and metrics to assess the impact of articles and authors. Grid and cloud computing provide new opportunities to offer better services in areas that require large CPU and storage resources including document Optical Character Recognition (OCR) processing, full-text indexing of articles and improved metrics. D4Science-II is a European project that develops and operates an e-Infrastructure supporting Virtual Research Environments (VREs). It develops an enabling technology (gCube) which implements a mechanism for facilitating the interoperation of its e-Infrastructure with other autonomously running data e-Infrastructures. As a result, this creates the core of an e-Infrastructure ecosystem. INSPIRE is one of the e-Infrastructures participating in D4Science-II project. In the context of the D4Science-II project, the INSPIRE e-Infrastructure makes available some of its resources and services to other members of the resulting ecosystem. Moreover, it benefits from the ecosystem via a dedicated Virtual Organization giving access to an array of resources ranging from computing and storage resources of grid infrastructures to data and services.

Human Brain inspired Artificial Intelligence & Developmental Robotics: A Review

Directory of Open Access Journals (Sweden)

Suresh Kumar

2017-06-01

Full Text Available Along with the developments in the field of the robotics, fascinating contributions and developments can be seen in the field of Artificial intelligence (AI. In this paper we will discuss about the developments is the field of artificial intelligence focusing learning algorithms inspired from the field of Biology, particularly large scale brain simulations, and developmental Psychology. We will focus on the emergence of the Developmental robotics and its significance in the field of AI.

Fish-inspired robots: design, sensing, actuation, and autonomy--a review of research.

Science.gov (United States)

Raj, Aditi; Thakur, Atul

2016-04-13

Underwater robot designs inspired by the behavior, physiology, and anatomy of fishes can provide enhanced maneuverability, stealth, and energy efficiency. Over the last two decades, robotics researchers have developed and reported a large variety of fish-inspired robot designs. The purpose of this review is to report different types of fish-inspired robot designs based upon their intended locomotion patterns. We present a detailed comparison of various design features like sensing, actuation, autonomy, waterproofing, and morphological structure of fish-inspired robots reported in the past decade. We believe that by studying the existing robots, future designers will be able to create new designs by adopting features from the successful robots. The review also summarizes the open research issues that need to be taken up for the further advancement of the field and also for the deployment of fish-inspired robots in practice.

Superstring-inspired SO(10) GUT model with intermediate scale

Science.gov (United States)

Sasaki, Ken

1987-12-01

A new mechanism is proposed for the mixing of Weinberg-Salam Higgs fields in superstring-inspired SO(10) models with no SO(10) singlet fields. The higher-dimensional terms in the superpotential can generate both Higgs field mixing and a small mass for the physical neutrino. I would like to thank Professor C. Iso for hospitality extended to me at the Tokyo Institute of Technology.

On Biblical Hebrew and Computer Science: Inspiration, Models, Tools, And Cross-fertilization

DEFF Research Database (Denmark)

Sandborg-Petersen, Ulrik

2011-01-01

Eep Talstra's work has been an inspiration to maby researchers, both within and outside of the field of Old Testament scholarship. Among others, Crist-Jan Doedens and the present author have been heavily influenced by Talstra in their own work within the field of computer science. The present...... of the present author. In addition, the tools surrounding Emdros, including SESB, Libronis, and the Emdros Query Tool, are described. Ecamples Biblical Hebrew scholar. Thus the inspiration of Talstra comes full-circle: from Biblical Hebrew databases to computer science and back into Biblical Hebrew scholarship....

Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

Science.gov (United States)

Marsh, Lorraine

2015-01-01

Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where "nonspecific" interactions contribute to biological function.

Nature-inspired computing and optimization theory and applications

CERN Document Server

Yang, Xin-She; Nakamatsu, Kazumi

2017-01-01

The book provides readers with a snapshot of the state of the art in the field of nature-inspired computing and its application in optimization. The approach is mainly practice-oriented: each bio-inspired technique or algorithm is introduced together with one of its possible applications. Applications cover a wide range of real-world optimization problems: from feature selection and image enhancement to scheduling and dynamic resource management, from wireless sensor networks and wiring network diagnosis to sports training planning and gene expression, from topology control and morphological filters to nutritional meal design and antenna array design. There are a few theoretical chapters comparing different existing techniques, exploring the advantages of nature-inspired computing over other methods, and investigating the mixing time of genetic algorithms. The book also introduces a wide range of algorithms, including the ant colony optimization, the bat algorithm, genetic algorithms, the collision-based opti...

Smart Nacre-inspired Nanocomposites.

Science.gov (United States)

Peng, Jingsong; Cheng, Qunfeng

2018-03-15

Nacre-inspired nanocomposites with excellent mechanical properties have achieved remarkable attention in the past decades. The high performance of nacre-inspired nanocomposites is a good basis for the further application of smart devices. Recently, some smart nanocomposites inspired by nacre have demonstrated good mechanical properties as well as effective and stable stimuli-responsive functions. In this Concept, we summarize the recent development of smart nacre-inspired nanocomposites, including 1D fibers, 2D films and 3D bulk nanocomposites, in response to temperature, moisture, light, strain, and so on. We show that diverse smart nanocomposites could be designed by combining various conventional fabrication methods of nacre-inspired nanocomposites with responsive building blocks and interface interactions. The nacre-inspired strategy is versatile for different kinds of smart nanocomposites in extensive applications, such as strain sensors, displays, artificial muscles, robotics, and so on, and may act as an effective roadmap for designing smart nanocomposites in the future. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Project-Based Biologically-Inspired Robotics Module

Science.gov (United States)

Crowder, R. M.; Zauner, K.-P.

2013-01-01

The design of any robotic system requires input from engineers from a variety of technical fields. This paper describes a project-based module, "Biologically-Inspired Robotics," that is offered to Electronics and Computer Science students at the University of Southampton, U.K. The overall objective of the module is for student groups to…

Coordination Chemistry of Linear Oligopyrrolic Fragments Inspired by Heme Metabolites

Science.gov (United States)

Gautam, Ritika

Linear oligopyrroles are degradation products of heme, which is converted in the presence of heme oxygenase to bile pigments, such as biliverdin and bilirubin. These tetrapyrrolic oligopyrroles are ubiquitously present in biological systems and find applications in the fields of catalysis and sensing. These linear tetrapyrrolic scaffolds are further degraded into linear tripyrrolic and dipyrrolic fragments. Although these lower oligopyrroles are abundantly present, their coordination chemistry requires further characterization. This dissertation focuses mainly on two classes of bioinspired linear oligopyrroles, propentdyopent and tripyrrindione, and their transition metal complexes, which present a rich ligand-based redox chemistry. Chapter 1 offers an overview of heme degradation to different classes of linear oligopyrroles and properties of their transition metal complexes. Chapter 2 is focused on the tripyrrin-1,14-dione scaffold of the urinary pigment uroerythrin, which coordinates divalent transition metals palladium and copper with square planar geometry. Specifically, the tripyrrin-1, 14-dione ligand binds Cu(II) and Pd(II) as a dianionic organic radical under ambient conditions. The electrochemical study confirms the presence of ligand based redox chemistry, and one electron oxidation or reduction reactions do not alter the planar geometry around the metal center. The X-Ray analysis and the electron paramagnetic resonance (EPR) studies of the complexes in the solid and solution phase reveals intermolecular interactions between the ligand based unpaired electrons and therefore formation of neutral pi-pi dimers. In Chapter 3, the antioxidant activity and the fluorescence sensor properties of the tripyrrin-1,14-dione ligand in the presence of superoxide are described. We found that the tripyrrindione ligand undergoes one-electron reduction in the presence of the superoxide radical anion (O2•- ) to form highly fluorescent H3TD1•- radical anion, which emits

[Mo2(CN)11]:5- A detailed description of ligand-field spectra and magnetic properties by first-principles calculations.

Science.gov (United States)

Hendrickx, Marc F A; Clima, S; Chibotaru, L F; Ceulemans, A

2005-10-06

An ab initio multiconfigurational approach has been used to calculate the ligand-field spectrum and magnetic properties of the title cyano-bridged dinuclear molybdenum complex. The rather large magnetic coupling parameter J for a single cyano bridge, as derived experimentally for this complex by susceptibility measurements, is confirmed to a high degree of accuracy by our CASPT2 calculations. Its electronic structure is rationalized in terms of spin-spin coupling between the two constituent hexacyano-monomolybdate complexes. An in-depth analysis on the basis of Anderson's kinetic exchange theory provides a qualitative picture of the calculated CASSCF antiferromagnetic ground-state eigenvector in the Mo dimer. Dynamic electron correlations as incorporated into our first-principles calculations by means of the CASPT2 method are essential to obtain quantitative agreement between theory and experiment.

Biomimetics as a Model for Inspiring Human Innovation

Science.gov (United States)

Bar-Cohen, Yoseph

2006-01-01

Electroactive polymers (EAP) are human made actuators that are the closest to mimic biological muscles. Technology was advanced to the level that biologically inspired robots are taking increasing roles in the world around us and making science fiction ideas a closer engineering reality. Artificial technologies (AI, AM, and others) are increasingly becoming practical tools for making biologically inspired devices and instruments with enormous potential for space applications. Polymer materials are used to produce figures that resemble human and animals. These materials are widely employed by the movie industry for making acting figures and by the orthopedic industry to construct cyborg components. There are still many challenges ahead that are critical to making such possibilities practical. The annual armwrestling contest is providing an exciting measure of how well advances in EAP are implemented to address the field challenges. There is a need to document natures inventions in an engineering form to possibly inspire new capabilities.

Towards Bio-Inspired Chromatic Behaviours in Surveillance Robots

Directory of Open Access Journals (Sweden)

Sampath Kumar Karutaa Gnaniar

2016-09-01

Full Text Available The field of Robotics is ever growing at the same time as posing enormous challenges. Numerous works has been done in biologically inspired robotics emulating models, systems and elements of nature for the purpose of solving traditional robotics problems. Chromatic behaviours are abundant in nature across a variety of living species to achieve camouflage, signaling, and temperature regulation. The ability of these creatures to successfully blend in with their environment and communicate by changing their colour is the fundamental inspiration for our research work. In this paper, we present dwarf chameleon inspired chromatic behaviour in the context of an autonomous surveillance robot, “PACHONDHI”. In our experiments, we successfully validated the ability of the robot to autonomously change its colour in relation to the terrain that it is traversing for maximizing detectability to friendly security agents and minimizing exposure to hostile agents, as well as to communicate with fellow cooperating robots.

AMMOS2: a web server for protein-ligand-water complexes refinement via molecular mechanics.

Science.gov (United States)

Labbé, Céline M; Pencheva, Tania; Jereva, Dessislava; Desvillechabrol, Dimitri; Becot, Jérôme; Villoutreix, Bruno O; Pajeva, Ilza; Miteva, Maria A

2017-07-03

AMMOS2 is an interactive web server for efficient computational refinement of protein-small organic molecule complexes. The AMMOS2 protocol employs atomic-level energy minimization of a large number of experimental or modeled protein-ligand complexes. The web server is based on the previously developed standalone software AMMOS (Automatic Molecular Mechanics Optimization for in silico Screening). AMMOS utilizes the physics-based force field AMMP sp4 and performs optimization of protein-ligand interactions at five levels of flexibility of the protein receptor. The new version 2 of AMMOS implemented in the AMMOS2 web server allows the users to include explicit water molecules and individual metal ions in the protein-ligand complexes during minimization. The web server provides comprehensive analysis of computed energies and interactive visualization of refined protein-ligand complexes. The ligands are ranked by the minimized binding energies allowing the users to perform additional analysis for drug discovery or chemical biology projects. The web server has been extensively tested on 21 diverse protein-ligand complexes. AMMOS2 minimization shows consistent improvement over the initial complex structures in terms of minimized protein-ligand binding energies and water positions optimization. The AMMOS2 web server is freely available without any registration requirement at the URL: http://drugmod.rpbs.univ-paris-diderot.fr/ammosHome.php. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Colloidal Quantum Dot Inks for Single-Step-Fabricated Field-Effect Transistors: The Importance of Postdeposition Ligand Removal.

Science.gov (United States)

Balazs, Daniel M; Rizkia, Nisrina; Fang, Hong-Hua; Dirin, Dmitry N; Momand, Jamo; Kooi, Bart J; Kovalenko, Maksym V; Loi, Maria Antonietta

2018-02-14

Colloidal quantum dots are a class of solution-processed semiconductors with good prospects for photovoltaic and optoelectronic applications. Removal of the surfactant, so-called ligand exchange, is a crucial step in making the solid films conductive, but performing it in solid state introduces surface defects and cracks in the films. Hence, the formation of thick, device-grade films have only been possible through layer-by-layer processing, limiting the technological interest for quantum dot solids. Solution-phase ligand exchange before the deposition allows for the direct deposition of thick, homogeneous films suitable for device applications. In this work, fabrication of field-effect transistors in a single step is reported using blade-coating, an upscalable, industrially relevant technique. Most importantly, a postdeposition washing step results in device properties comparable to the best layer-by-layer processed devices, opening the way for large-scale fabrication and further interest from the research community.

Bio-inspired approach for intelligent unattended ground sensors

Science.gov (United States)

Hueber, Nicolas; Raymond, Pierre; Hennequin, Christophe; Pichler, Alexander; Perrot, Maxime; Voisin, Philippe; Moeglin, Jean-Pierre

2015-05-01

Improving the surveillance capacity over wide zones requires a set of smart battery-powered Unattended Ground Sensors capable of issuing an alarm to a decision-making center. Only high-level information has to be sent when a relevant suspicious situation occurs. In this paper we propose an innovative bio-inspired approach that mimics the human bi-modal vision mechanism and the parallel processing ability of the human brain. The designed prototype exploits two levels of analysis: a low-level panoramic motion analysis, the peripheral vision, and a high-level event-focused analysis, the foveal vision. By tracking moving objects and fusing multiple criteria (size, speed, trajectory, etc.), the peripheral vision module acts as a fast relevant event detector. The foveal vision module focuses on the detected events to extract more detailed features (texture, color, shape, etc.) in order to improve the recognition efficiency. The implemented recognition core is able to acquire human knowledge and to classify in real-time a huge amount of heterogeneous data thanks to its natively parallel hardware structure. This UGS prototype validates our system approach under laboratory tests. The peripheral analysis module demonstrates a low false alarm rate whereas the foveal vision correctly focuses on the detected events. A parallel FPGA implementation of the recognition core succeeds in fulfilling the embedded application requirements. These results are paving the way of future reconfigurable virtual field agents. By locally processing the data and sending only high-level information, their energy requirements and electromagnetic signature are optimized. Moreover, the embedded Artificial Intelligence core enables these bio-inspired systems to recognize and learn new significant events. By duplicating human expertise in potentially hazardous places, our miniature visual event detector will allow early warning and contribute to better human decision making.

Contradiction analysis: towards a dialectical approach in ergonomics field interventions

Directory of Open Access Journals (Sweden)

Dimitris Nathanael

2015-03-01

Full Text Available The present paper is a methodological contribution to the ergonomics field intervention process. It proposes a perspective on work analysis based on the dialectics notion of contradictions. Contradiction analysis is proposed as being complementary to more established work decomposition methods. The aim of including such an analysis is to frame various heterogeneous determinants of a work activity in practical terms, swiftly and in a manner that preserves its multifaceted unity and essence. Such framing is of particular value when considering alternative design solutions because it provides a practical means for anticipating the effects and side effects of proposed changes. The proposed method is inspired by two theoretical constructs: (i contradiction, as used in Cultural Historical Activity Theory, and (ii regulation, as developed and used by the francophone tradition of the ergonomics of activity. Two brief examples of its use are presented, and its usefulness, possible pitfalls and need for further developments are discussed.

Intuitive Density Functional Theory-Based Energy Decomposition Analysis for Protein-Ligand Interactions.

Science.gov (United States)

Phipps, M J S; Fox, T; Tautermann, C S; Skylaris, C-K

2017-04-11

First-principles quantum mechanical calculations with methods such as density functional theory (DFT) allow the accurate calculation of interaction energies between molecules. These interaction energies can be dissected into chemically relevant components such as electrostatics, polarization, and charge transfer using energy decomposition analysis (EDA) approaches. Typically EDA has been used to study interactions between small molecules; however, it has great potential to be applied to large biomolecular assemblies such as protein-protein and protein-ligand interactions. We present an application of EDA calculations to the study of ligands that bind to the thrombin protein, using the ONETEP program for linear-scaling DFT calculations. Our approach goes beyond simply providing the components of the interaction energy; we are also able to provide visual representations of the changes in density that happen as a result of polarization and charge transfer, thus pinpointing the functional groups between the ligand and protein that participate in each kind of interaction. We also demonstrate with this approach that we can focus on studying parts (fragments) of ligands. The method is relatively insensitive to the protocol that is used to prepare the structures, and the results obtained are therefore robust. This is an application to a real protein drug target of a whole new capability where accurate DFT calculations can produce both energetic and visual descriptors of interactions. These descriptors can be used to provide insights for tailoring interactions, as needed for example in drug design.

Non-empirical Prediction of the Photophysical and Magnetic Properties of Systems with Open d- and f-Shells Based on Combined Ligand Field and Density Functional Theory (LFDFT).

Science.gov (United States)

Daul, Claude

2014-09-01

Despite the important growth of ab initio and computational techniques, ligand field theory in molecular science or crystal field theory in condensed matter offers the most intuitive way to calculate multiplet energy levels arising from systems with open shells d and/or f electrons. Over the past decade we have developed a ligand field treatment of inorganic molecular modelling taking advantage of the dominant localization of the frontier orbitals within the metal-sphere. This feature, which is observed in any inorganic coordination compound, especially if treated by Density Functional Theory calculation, allows the determination of the electronic structure and properties with a surprising good accuracy. In ligand field theory, the theoretical concepts consider only a single atom center; and treat its interaction with the chemical environment essentially as a perturbation. Therefore success in the simple ligand field theory is no longer questionable, while the more accurate molecular orbital theory does in general over-estimate the metal-ligand covalence, thus yields wave functions that are too delocalized. Although LF theory has always been popular as a semi-empirical method when dealing with molecules of high symmetry e.g. cubic symmetry where the number of parameters needed is reasonably small (3 or 5), this is no more the case for molecules without symmetry and involving both an open d- and f-shell (# parameters ∼90). However, the combination of LF theory and Density Functional (DF) theory that we introduced twenty years ago can easily deal with complex molecules of any symmetry with two and more open shells. The accuracy of these predictions from 1(st) principles achieves quite a high accuracy (<5%) in terms of states energies. Hence, this approach is well suited to predict the magnetic and photo-physical properties arbitrary molecules and materials prior to their synthesis, which is the ultimate goal of each computational chemist. We will illustrate the

Bio-inspired networking

CERN Document Server

Câmara, Daniel

2015-01-01

Bio-inspired techniques are based on principles, or models, of biological systems. In general, natural systems present remarkable capabilities of resilience and adaptability. In this book, we explore how bio-inspired methods can solve different problems linked to computer networks. Future networks are expected to be autonomous, scalable and adaptive. During millions of years of evolution, nature has developed a number of different systems that present these and other characteristics required for the next generation networks. Indeed, a series of bio-inspired methods have been successfully used to solve the most diverse problems linked to computer networks. This book presents some of these techniques from a theoretical and practical point of view. Discusses the key concepts of bio-inspired networking to aid you in finding efficient networking solutions Delivers examples of techniques both in theoretical concepts and practical applications Helps you apply nature's dynamic resource and task management to your co...

Efficacy of the semiempirical sparkle model as compared to ECP ab-initio calculations for the prediction of ligand field parameters of europium (III) complexes

International Nuclear Information System (INIS)

Freire, Ricardo O.; Rocha, Gerd B.; Albuquerque, Rodrigo Q.; Simas, Alfredo M.

2005-01-01

The second version of the sparkle model for the calculation of lanthanide complexes (SMLC II) as well as ab-initio calculations (HF/STO-3G and HF/3-21G) have been used to calculate the geometries of a series of europium (III) complexes with different coordination numbers (CN=7, 8 and 9), ligating atoms (O and N) and ligands (mono, bi and polydentate). The so-called ligand field parameters, Bqk's, have been calculated from both SMLC II and ab-initio optimized structures and compared to the ones calculated from crystallographic data. The results show that the SMLC II model represents a significant improvement over the previous version (SMLC) and has given good results when compared to ab-initio methods, which demand a much higher computational effort. Indeed, ab-initio methods take around a hundred times more computing time than SMLC. As such, our results indicate that our sparkle model can be a very useful and a fast tool when applied to the prediction of both ground state geometries and ligand field parameters of europium (III) complexes

Ships - inspiring objects in architecture

Science.gov (United States)

Marczak, Elzbieta

2017-10-01

Sea-going vessels have for centuries fascinated people, not only those who happen to work at sea, but first and foremost, those who have never set foot aboard a ship. The environment in which ships operate is reminiscent of freedom and countless adventures, but also of hard and interesting maritime working life. The famous words of Pompey: “Navigare necesseest, vivere non estnecesse” (sailing is necessary, living - is not necessary), which he pronounced on a stormy sea voyage, arouse curiosity and excitement, inviting one to test the truth of this saying personally. It is often the case, however, that sea-faring remains within the realm of dreams, while the fascination with ships demonstrates itself through a transposition of naval features onto land constructions. In such cases, ship-inspired motifs bring alive dreams and yearnings as well as reflect tastes. Tourism is one of the indicators of people’s standard of living and a measure of a society’s civilisation. Maritime tourism has been developing rapidly in recent decades. A sea cruise offers an insight into life at sea. Still, most people derive their knowledge of passenger vessels and their furnishings from the mass media. Passenger vessels, also known as “floating cities,” are described as majestic and grand, while their on-board facilities as luxurious, comfortable, exclusive and inaccessible to common people on land. Freight vessels, on the other hand, are described as enormous objects which dwarf the human being into insignificance. This article presents the results of research intended to answer the following questions: what makes ships a source of inspiration for land architecture? To what extent and by what means do architects draw on ships in their design work? In what places can we find structures inspired by ships? What ships inspire architects? This article presents examples of buildings, whose design was inspired by the architecture and structural details of sea vessels. An analysis of

Touchable Computing: Computing-Inspired Bio-Detection.

Science.gov (United States)

Chen, Yifan; Shi, Shaolong; Yao, Xin; Nakano, Tadashi

2017-12-01

We propose a new computing-inspired bio-detection framework called touchable computing (TouchComp). Under the rubric of TouchComp, the best solution is the cancer to be detected, the parameter space is the tissue region at high risk of malignancy, and the agents are the nanorobots loaded with contrast medium molecules for tracking purpose. Subsequently, the cancer detection procedure (CDP) can be interpreted from the computational optimization perspective: a population of externally steerable agents (i.e., nanorobots) locate the optimal solution (i.e., cancer) by moving through the parameter space (i.e., tissue under screening), whose landscape (i.e., a prescribed feature of tissue environment) may be altered by these agents but the location of the best solution remains unchanged. One can then infer the landscape by observing the movement of agents by applying the "seeing-is-sensing" principle. The term "touchable" emphasizes the framework's similarity to controlling by touching the screen with a finger, where the external field for controlling and tracking acts as the finger. Given this analogy, we aim to answer the following profound question: can we look to the fertile field of computational optimization algorithms for solutions to achieve effective cancer detection that are fast, accurate, and robust? Along this line of thought, we consider the classical particle swarm optimization (PSO) as an example and propose the PSO-inspired CDP, which differs from the standard PSO by taking into account realistic in vivo propagation and controlling of nanorobots. Finally, we present comprehensive numerical examples to demonstrate the effectiveness of the PSO-inspired CDP for different blood flow velocity profiles caused by tumor-induced angiogenesis. The proposed TouchComp bio-detection framework may be regarded as one form of natural computing that employs natural materials to compute.

Ligand-field symmetry effects in Fe(ii) polypyridyl compounds probed by transient X-ray absorption spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Cho, Hana; Strader, Matthew L.; Hong, Kiryong; Jamula, Lindsey; Gullikson, Eric M.; Kim, Tae Kyu; de Groot, Frank M. F.; McCusker, James K.; Schoenlein, Robert W.; Huse, Nils

2012-01-01

Ultrafast excited-state evolution in polypyridyl FeII complexes are of fundamental interest for understanding the origins of the sub-ps spin-state changes that occur upon photoexcitation of this class of compounds as well as for the potential impact such ultrafast dynamics have on incorporation of these compounds in solar energy conversion schemes or switchable optical storage technologies. We have demonstrated that ground-state and, more importantly, ultrafast time-resolved x-ray absorption methods can offer unique insights into the interplay between electronic and geometric structure that underpin the photo-induced dynamics of this class of compounds. The present contribution examines in greater detail how the symmetry of the ligand field surrounding the metal ion can be probed using these x-ray techniques. In particular, we show that steady-state K-edge spectroscopy of the nearest-neighbour nitrogen atoms reveals the characteristic chemical environment of the respective ligands and suggests an interesting target for future charge-transfer femtosecond and attosecond spectroscopy in the x-ray water window.

An Approach for Calculating Land Valuation by Using Inspire Data Models

Science.gov (United States)

Aydinoglu, A. C.; Bovkir, R.

2017-11-01

Land valuation is a highly important concept for societies and governments have always emphasis on the process especially for taxation, expropriation, market capitalization and economic activity purposes. To success an interoperable and standardised land valuation, INSPIRE data models can be very practical and effective. If data used in land valuation process produced in compliance with INSPIRE specifications, a reliable and effective land valuation process can be performed. In this study, possibility of the performing land valuation process with using the INSPIRE data models was analysed and with the help of Geographic Information Systems (GIS) a case study in Pendik was implemented. For this purpose, firstly data analysis and gathering was performed. After, different data structures were transformed according to the INSPIRE data model requirements. For each data set necessary ETL (Extract-Transform-Load) tools were produced and all data transformed according to the target data requirements. With the availability and practicability of spatial analysis tools of GIS software, land valuation calculations were performed for study area.

Analysis of protein-protein docking decoys using interaction fingerprints: application to the reconstruction of CaM-ligand complexes

Directory of Open Access Journals (Sweden)

Uchikoga Nobuyuki

2010-05-01

Full Text Available Abstract Background Protein-protein docking for proteins with large conformational changes was analyzed by using interaction fingerprints, one of the scales for measuring similarities among complex structures, utilized especially for searching near-native protein-ligand or protein-protein complex structures. Here, we have proposed a combined method for analyzing protein-protein docking by taking large conformational changes into consideration. This combined method consists of ensemble soft docking with multiple protein structures, refinement of complexes, and cluster analysis using interaction fingerprints and energy profiles. Results To test for the applicability of this combined method, various CaM-ligand complexes were reconstructed from the NMR structures of unbound CaM. For the purpose of reconstruction, we used three known CaM-ligands, namely, the CaM-binding peptides of cyclic nucleotide gateway (CNG, CaM kinase kinase (CaMKK and the plasma membrane Ca2+ ATPase pump (PMCA, and thirty-one structurally diverse CaM conformations. For each ligand, 62000 CaM-ligand complexes were generated in the docking step and the relationship between their energy profiles and structural similarities to the native complex were analyzed using interaction fingerprint and RMSD. Near-native clusters were obtained in the case of CNG and CaMKK. Conclusions The interaction fingerprint method discriminated near-native structures better than the RMSD method in cluster analysis. We showed that a combined method that includes the interaction fingerprint is very useful for protein-protein docking analysis of certain cases.

Ligand design for riboswitches, an emerging target class for novel antibiotics.

Science.gov (United States)

Rekand, Illimar Hugo; Brenk, Ruth

2017-09-01

Riboswitches are cis-acting gene regulatory elements and constitute potential targets for new antibiotics. Recent studies in this field have started to explore these targets for drug discovery. New ligands found by fragment screening, design of analogs of the natural ligands or serendipitously by phenotypic screening have shown antibacterial effects in cell assays against a range of bacteria strains and in animal models. In this review, we highlight the most advanced drug design work of riboswitch ligands and discuss the challenges in the field with respect to the development of antibiotics with a new mechanism of action.

Inspiration from britain?

DEFF Research Database (Denmark)

Vagnby, Bo

2008-01-01

Danish housing policy needs a dose of renewed social concern - and could find new inspiration in Britain's housing and urban planning policies, says Bo Vagnby. Udgivelsesdato: November......Danish housing policy needs a dose of renewed social concern - and could find new inspiration in Britain's housing and urban planning policies, says Bo Vagnby. Udgivelsesdato: November...

Ligand field and interference effects in L-edge X-ray Raman scattering of MnF{sub 2} and CoF{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Jimenez M, J.; Herrera P, G. M.; Olalde V, P. [Instituto de Ciencias Nucleares, UNAM, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Ederer, D. L.; Schuler, T. [Department of Physics, Tulane University, New Orleans, LA 70118 (United States)

2008-02-15

We present experimental results for x-ray absorption and resonant emission at the L-edge of the transition metal in MnF{sub 2} and CoF{sub 2}. The emission data are corrected for self-absorption. The data are compared with calculations in both the free-ion approximation and with the effect of the ligand field of D{sub 4h} symmetry included. The results of the calculations take into account interference terms in the Kramers-Heisenberg expression. We obtain very good agreement between experiment and theory for both x-ray absorption and resonant emission in the two compounds. The inclusion of the ligand field is important to achieve such agreement. However, the results of the calculation that does not take into account the interference terms are in better agreement with experiment, indicating that the model used probably overestimates the importance of interference effects. (Author)

6th International Conference on Innovations in Bio-Inspired Computing and Applications

CERN Document Server

Abraham, Ajith; Krömer, Pavel; Pant, Millie; Muda, Azah

2016-01-01

This Volume contains the papers presented during the 6th International Conference on Innovations in Bio-Inspired Computing and Applications IBICA 2015 which was held in Kochi, India during December 16-18, 2015. The 51 papers presented in this Volume were carefully reviewed and selected. The 6th International Conference IBICA 2015 has been organized to discuss the state-of-the-art as well as to address various issues in the growing research field of Bio-inspired Computing which is currently one of the most exciting research areas, and is continuously demonstrating exceptional strength in solving complex real life problems. The Volume will be a valuable reference to researchers, students and practitioners in the computational intelligence field.

Sound Classification in Hearing Aids Inspired by Auditory Scene Analysis

Science.gov (United States)

Büchler, Michael; Allegro, Silvia; Launer, Stefan; Dillier, Norbert

2005-12-01

A sound classification system for the automatic recognition of the acoustic environment in a hearing aid is discussed. The system distinguishes the four sound classes "clean speech," "speech in noise," "noise," and "music." A number of features that are inspired by auditory scene analysis are extracted from the sound signal. These features describe amplitude modulations, spectral profile, harmonicity, amplitude onsets, and rhythm. They are evaluated together with different pattern classifiers. Simple classifiers, such as rule-based and minimum-distance classifiers, are compared with more complex approaches, such as Bayes classifier, neural network, and hidden Markov model. Sounds from a large database are employed for both training and testing of the system. The achieved recognition rates are very high except for the class "speech in noise." Problems arise in the classification of compressed pop music, strongly reverberated speech, and tonal or fluctuating noises.

Synthesis, spectral, thermal and biological studies of mixed ligand complexes with newly prepared Schiff base and 1,10-phenanthroline ligands

Science.gov (United States)

Abd El-Halim, Hanan F.; Mohamed, Gehad G.; Khalil, Eman A. M.

2017-10-01

A series of mixed ligand complexes were prepared from the Schiff base (L1) as a primary ligand, prepared by condensation of oxamide and furan-2-carbaldehyde, and 1,10-phenanthroline (1,10-phen) as a secondary ligand. The Schiff base ligand and its mixed ligand chelates were characterized based on elemental analysis, IR, 1H NMR, thermal analysis, UV-Visible, mass, molar conductance, magnetic moment. X-ray diffraction, solid reflectance and ESR also have been studied. The mixed ligand complexes were found to have the formulae of [M(L1) (1,10-phen)]Clm.nH2O (M = Cr(III) and Fe(III) (m = 3) (n = 0); M = Mn(II), Cu(II) and Cd(II) (m = 2) (n = 0); and M = Co(II) (m = 2) (n = 1), Ni(II) (m = 2) (n = 2) and Zn(II) (m = 2) (n = 3)) and that the geometrical structure of the complexes were octahedral. The parameters of thermodynamic using Coats-Redfern and Horowitz-Metzger equations were calculated. The synthesized Schiff base ligand, 1,10-phenanthroline ligand and Their mixed ligand complexes were also investigated for their antibacterial and antifungal activity against bacterial species (Gram-Ve bacteria: Pseudomonas aeruginosa and Escherichia coli) and (Gram + Ve bacteria: Bacillus subtilis and Streptococcus pneumonia) and fungi (Aspergillus fumigates and Candida albicans). The anticancer activity of the new compounds had been tested against breast (MFC7) and colon (HCT-116) cell lines. The results showed high activity for the synthesized compounds.

Bio-Inspired Nitrile Hydration by Peptidic Ligands Based on L-Cysteine, L-Methionine or L-Penicillamine and Pyridine-2,6-dicarboxylic Acid

Directory of Open Access Journals (Sweden)

Cillian Byrne

2014-12-01

Full Text Available Nitrile hydratase (NHase, EC 4.2.1.84 is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III- and iron(III-dependent NHases reveal an unusual metal binding motif made up from six sequential amino acids and comprising two amide nitrogens from the peptide backbone and three cysteine-derived sulfur ligands, each at a different oxidation state (thiolate, sulfenate and sulfinate. Based on the active site geometry revealed by these crystal structures, we have designed a series of small-molecule ligands which integrate essential features of the NHase metal binding motif into a readily accessible peptide environment. We report the synthesis of ligands based on a pyridine-2,6-dicarboxylic acid scaffold and L-cysteine, L-S-methylcysteine, L-methionine or L-penicillamine. These ligands have been combined with cobalt(III and iron(III and tested as catalysts for biomimetic nitrile hydration. The highest levels of activity are observed with the L-penicillamine ligand which, in combination with cobalt(III, converts acetonitrile to acetamide at 1.25 turnovers and benzonitrile to benzamide at 1.20 turnovers.

Bio-inspired CO2 reduction by a rhenium tricarbonyl bipyridine-based catalyst appended to amino acids and peptidic platforms: incorporating proton relays and hydrogen-bonding functional groups.

Science.gov (United States)

Chabolla, S A; Machan, C W; Yin, J; Dellamary, E A; Sahu, S; Gianneschi, N C; Gilson, M K; Tezcan, F A; Kubiak, C P

2017-06-02

Herein, we report a new approach to bio-inspired catalyst design. The molecular catalyst employed in these studies is based on the robust and selective Re(bpy)(CO) 3 Cl-type (bpy = 2,2'-bipyridine) homogeneous catalysts, which have been extensively studied for their ability to reduce CO 2 electrochemically or photochemically in the presence of a photosensitizer. These catalysts can be highly active photocatalysts in their own right. In this work, the bipyridine ligand was modified with amino acids and synthetic peptides. These results build on earlier findings wherein the bipyridine ligand was functionalized with amide groups to promote dimer formation and CO 2 reduction by an alternate bimolecular mechanism at lower overpotential (ca. 250 mV) than the more commonly observed unimolecular process. The bio-inspired catalysts were designed to allow for the incorporation of proton relays to support reduction of CO 2 to CO and H 2 O. The coupling of amino acids tyrosine and phenylalanine led to the formation of two structurally similar Re catalyst/peptide catalysts for comparison of proton transport during catalysis. This article reports the synthesis and characterization of novel catalyst/peptide hybrids by molecular dynamics (MD simulations of structural dynamics), NMR studies of solution phase structures, and electrochemical studies to measure the activities of new bio-inspired catalysts in the reduction of CO 2.

Mixed-ligand Pt(II) dithione-dithiolato complexes: influence of the dicyanobenzodithiolato ligand on the second-order NLO properties.

Science.gov (United States)

Espa, Davide; Pilia, Luca; Marchiò, Luciano; Artizzu, Flavia; Serpe, Angela; Mercuri, Maria Laura; Simão, Dulce; Almeida, Manuel; Pizzotti, Maddalena; Tessore, Francesca; Deplano, Paola

2012-03-28

The mixed-ligand dithiolene complex [Pt(Bz(2)pipdt)(dcbdt)] (1) bearing the two ligands Bz(2)pipdt = 1,4-dibenzyl-piperazine-3,2-dithione and dcbdt = dicyanobenzodithiolato, has been synthesized, characterized and studied to evaluate its second-order optical nonlinearity. The dithione/dithiolato character of the two ligands gives rise to an asymmetric distribution of the charge in the molecule. This is reflected by structural data showing that in the C(2)S(2)PtS(2)C(2) dithiolene core the four sulfur atoms define a square-planar coordination environment of the metal where the Pt-S bond distances involving the two ligands are similar, while the C-S bond distances in the C(2)S(2) units exhibit a significant difference in Bz(2)pipdt (dithione) and dcbdt (dithiolato). 1 shows a moderately strong absorption peak in the visible region, which can be related to a HOMO-LUMO transition, where the dcbdt ligand (dithiolato) contributes mostly to the HOMO, and the Bz(2)pipdt one (dithione) mostly to the LUMO. Thus this transition has ligand-to-ligand charge transfer (CT) character with some contribution of the metal and undergoes negative solvatochromism and molecular quadratic optical nonlinearity (μβ(0) = -1296 × 10(-48) esu), which was determined by the EFISH (electric-field-induced second-harmonic generation) technique and compared with the values of similar complexes on varying the dithiolato ligand (mnt = maleonitriledithiolato, dmit = 2-thioxo-1,3-dithiole-4,5-dithiolato). Theoretical calculations help to elucidate the role of the dithiolato ligands in affecting the molecular quadratic optical nonlinearity of these complexes.

Origin of the Anomalous Color of Egyptian and Han Blue Historical Pigments: Going beyond the Complex Approximation in Ligand Field Theory

Science.gov (United States)

García-Fernandez, Pablo; Moreno, Miguel; Aramburu, José Antonio

2016-01-01

The complex approximation is widely used in the framework of the Ligand Field Theory for explaining the optical properties of crystalline coordination compounds. Here, we show that there are essential features of these systems that cannot be understood with the usual approximation that only considers an isolated complex at the correct equilibrium…

A Tony Thomas-Inspired Guide to INSPIRE

Energy Technology Data Exchange (ETDEWEB)

O' Connell, Heath B.; /Fermilab

2010-04-01

The SPIRES database was created in the late 1960s to catalogue the high energy physics preprints received by the SLAC Library. In the early 1990s it became the first database on the web and the first website outside of Europe. Although indispensible to the HEP community, its aging software infrastructure is becoming a serious liability. In a joint project involving CERN, DESY, Fermilab and SLAC, a new database, INSPIRE, is being created to replace SPIRES using CERN's modern, open-source Invenio database software. INSPIRE will maintain the content and functionality of SPIRES plus many new features. I describe this evolution from the birth of SPIRES to the current day, noting that the career of Tony Thomas spans this timeline.

A Tony Thomas-Inspired Guide to INSPIRE

International Nuclear Information System (INIS)

O'Connell, Heath B.

2010-01-01

The SPIRES database was created in the late 1960s to catalogue the high energy physics preprints received by the SLAC Library. In the early 1990s it became the first database on the web and the first website outside of Europe. Although indispensible to the HEP community, its aging software infrastructure is becoming a serious liability. In a joint project involving CERN, DESY, Fermilab and SLAC, a new database, INSPIRE, is being created to replace SPIRES using CERN's modern, open-source Invenio database software. INSPIRE will maintain the content and functionality of SPIRES plus many new features. I describe this evolution from the birth of SPIRES to the current day, noting that the career of Tony Thomas spans this timeline.

Optic flow estimation on trajectories generated by bio-inspired closed-loop flight.

Science.gov (United States)

Shoemaker, Patrick A; Hyslop, Andrew M; Humbert, J Sean

2011-05-01

We generated panoramic imagery by simulating a fly-like robot carrying an imaging sensor, moving in free flight through a virtual arena bounded by walls, and containing obstructions. Flight was conducted under closed-loop control by a bio-inspired algorithm for visual guidance with feedback signals corresponding to the true optic flow that would be induced on an imager (computed by known kinematics and position of the robot relative to the environment). The robot had dynamics representative of a housefly-sized organism, although simplified to two-degree-of-freedom flight to generate uniaxial (azimuthal) optic flow on the retina in the plane of travel. Surfaces in the environment contained images of natural and man-made scenes that were captured by the moving sensor. Two bio-inspired motion detection algorithms and two computational optic flow estimation algorithms were applied to sequences of image data, and their performance as optic flow estimators was evaluated by estimating the mutual information between outputs and true optic flow in an equatorial section of the visual field. Mutual information for individual estimators at particular locations within the visual field was surprisingly low (less than 1 bit in all cases) and considerably poorer for the bio-inspired algorithms that the man-made computational algorithms. However, mutual information between weighted sums of these signals and comparable sums of the true optic flow showed significant increases for the bio-inspired algorithms, whereas such improvement did not occur for the computational algorithms. Such summation is representative of the spatial integration performed by wide-field motion-sensitive neurons in the third optic ganglia of flies.

On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

International Nuclear Information System (INIS)

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian; Roitberg, Adrian E.

2015-01-01

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data

On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

Energy Technology Data Exchange (ETDEWEB)

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian, E-mail: sfalberti@gmail.com [Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal (Argentina); Roitberg, Adrian E. [Departments of Physics and Chemistry, University of Florida, Gainesville, Florida 32611 (United States)

2015-06-28

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima.

Science.gov (United States)

Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Alexey V; Kutov, Danil C; Sobolev, Sergey I; Voevodin, Vladimir V; Sulimov, Vladimir B

2015-01-01

The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima

Directory of Open Access Journals (Sweden)

Igor V. Oferkin

2015-01-01

Full Text Available The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

Hair-based flow-sensing inspired by the cricket cercal system

NARCIS (Netherlands)

Krijnen, Gijsbertus J.M.; Droogendijk, H.; Steinmann, T.; Dagamseh, A.M.K.; Jaganatharaja, R.K.; Casas, J.

2014-01-01

Micro Electro Mechanical Systems (MEMS) offer exciting possibilities for the fabri­cation of bioinspired mechanosensors. Over the last years we have been working on cricket inspired hair-sensor arrays for spatio-temporal flow-field observations (i.e., flow-cameras) and source localization. Whereas

Water as a complex system: its role in ligand diffusion, general anesthesia, and sleep.

Science.gov (United States)

Kier, Lemont B

2007-10-01

The work and inspiration of Robert Rosen is stated and expressed in personal tones. The concept of passages through water (H2O) near protein surfaces is reviewed in terms of its influence on ligand diffusion to an effector. This is offered as a target for interference by a non-specific general anesthetic agent. In view of the similarities between this anesthetic state and sleep, this mechanism is proposed to be operative for the sleep/wake states. Based on this mechanism and other factors, nitrogen (N2) is proposed as an exogenous sleep factor.

Seismic analysis of ITER fourth PF (Poloidal Field Coil) feeder

International Nuclear Information System (INIS)

Liu, Sumei; Chen, Wei; Song, Yuntao; Ni, Xiaojun; Wang, Zhongwei; Chen, Yonghua; Gong, Chenyu

2014-01-01

The ITER feeder systems connect the ITER magnet systems located inside the main cryostat to the cryo-plant, power-supply and control system interfaces outside the cryostat. The main purpose of the feeders is to convey the cryogenic supply and electrical power to the coils as well as house the instrumentation wiring. The PF busbar which carries 52 kA current will suffer from high Lorentz force due to the background magnetic field inspired by the coils and the self-field between every pair of busbars. Except their mechanical strength and thermal insulation performance must be achieved, the dynamic mechanism on PF structure should be assessed. This paper presents the simulation and seismic analysis on ITER 4th PF feeder including the Coil Terminal Box and S-bend Box (CTB and SBB), the Cryostat Feed-through (CFT), the In-Cryostat-Feeder (ICF), especially for the ground supports and main outer-tube firstly. This analysis aims to study seismic resistance on system design under local seismograms with floor response spectrum, the structural response vibration mode and response duration results of displacement, membrane stress, and bending stress on structure under different directions actuating signals were obtained by using the single-seismic spectrum analysis and Dead Weight analysis respectively. Based on the simulative and analytical results, the system seismic resistance and the integrity of the support structure in the 4th PF feeder have been studied and the detail design confirmed

Consistent two-dimensional visualization of protein-ligand complex series

Directory of Open Access Journals (Sweden)

Stierand Katrin

2011-06-01

Full Text Available Abstract Background The comparative two-dimensional graphical representation of protein-ligand complex series featuring different ligands bound to the same active site offers a quick insight in their binding mode differences. In comparison to arbitrary orientations of the residue molecules in the individual complex depictions a consistent placement improves the legibility and comparability within the series. The automatic generation of such consistent layouts offers the possibility to apply it to large data sets originating from computer-aided drug design methods. Results We developed a new approach, which automatically generates a consistent layout of interacting residues for a given series of complexes. Based on the structural three-dimensional input information, a global two-dimensional layout for all residues of the complex ensemble is computed. The algorithm incorporates the three-dimensional adjacencies of the active site residues in order to find an universally valid circular arrangement of the residues around the ligand. Subsequent to a two-dimensional ligand superimposition step, a global placement for each residue is derived from the set of already placed ligands. The method generates high-quality layouts, showing mostly overlap-free solutions with molecules which are displayed as structure diagrams providing interaction information in atomic detail. Application examples document an improved legibility compared to series of diagrams whose layouts are calculated independently from each other. Conclusions The presented method extends the field of complex series visualizations. A series of molecules binding to the same protein active site is drawn in a graphically consistent way. Compared to existing approaches these drawings substantially simplify the visual analysis of large compound series.

Evaluation of the novel algorithm of flexible ligand docking with moveable target-protein atoms.

Science.gov (United States)

Sulimov, Alexey V; Zheltkov, Dmitry A; Oferkin, Igor V; Kutov, Danil C; Katkova, Ekaterina V; Tyrtyshnikov, Eugene E; Sulimov, Vladimir B

2017-01-01

We present the novel docking algorithm based on the Tensor Train decomposition and the TT-Cross global optimization. The algorithm is applied to the docking problem with flexible ligand and moveable protein atoms. The energy of the protein-ligand complex is calculated in the frame of the MMFF94 force field in vacuum. The grid of precalculated energy potentials of probe ligand atoms in the field of the target protein atoms is not used. The energy of the protein-ligand complex for any given configuration is computed directly with the MMFF94 force field without any fitting parameters. The conformation space of the system coordinates is formed by translations and rotations of the ligand as a whole, by the ligand torsions and also by Cartesian coordinates of the selected target protein atoms. Mobility of protein and ligand atoms is taken into account in the docking process simultaneously and equally. The algorithm is realized in the novel parallel docking SOL-P program and results of its performance for a set of 30 protein-ligand complexes are presented. Dependence of the docking positioning accuracy is investigated as a function of parameters of the docking algorithm and the number of protein moveable atoms. It is shown that mobility of the protein atoms improves docking positioning accuracy. The SOL-P program is able to perform docking of a flexible ligand into the active site of the target protein with several dozens of protein moveable atoms: the native crystallized ligand pose is correctly found as the global energy minimum in the search space with 157 dimensions using 4700 CPU ∗ h at the Lomonosov supercomputer.

Viscous-Inviscid Methods in Unsteady Aerodynamic Analysis of Bio-Inspired Morphing Wings

Science.gov (United States)

Dhruv, Akash V.

Flight has been one of the greatest realizations of human imagination, revolutionizing communication and transportation over the years. This has greatly influenced the growth of technology itself, enabling researchers to communicate and share their ideas more effectively, extending the human potential to create more sophisticated systems. While the end product of a sophisticated technology makes our lives easier, its development process presents an array of challenges in itself. In last decade, scientists and engineers have turned towards bio-inspiration to design more efficient and robust aerodynamic systems to enhance the ability of Unmanned Aerial Vehicles (UAVs) to be operated in cluttered environments, where tight maneuverability and controllability are necessary. Effective use of UAVs in domestic airspace will mark the beginning of a new age in communication and transportation. The design of such complex systems necessitates the need for faster and more effective tools to perform preliminary investigations in design, thereby streamlining the design process. This thesis explores the implementation of numerical panel methods for aerodynamic analysis of bio-inspired morphing wings. Numerical panel methods have been one of the earliest forms of computational methods for aerodynamic analysis to be developed. Although the early editions of this method performed only inviscid analysis, the algorithm has matured over the years as a result of contributions made by prominent aerodynamicists. The method discussed in this thesis is influenced by recent advancements in panel methods and incorporates both viscous and inviscid analysis of multi-flap wings. The surface calculation of aerodynamic coefficients makes this method less computationally expensive than traditional Computational Fluid Dynamics (CFD) solvers available, and thus is effective when both speed and accuracy are desired. The morphing wing design, which consists of sequential feather-like flaps installed

Zinc acetylacetonate hydrate adducted with nitrogen donor ligands: Synthesis, spectroscopic characterization, and thermal analysis

Science.gov (United States)

Brahma, Sanjaya; Shivashankar, S. A.

2015-12-01

We report synthesis, spectroscopic characterization, and thermal analysis of zinc acetylacetonate complex adducted by nitrogen donor ligands, such as pyridine, bipyridine, and phenanthroline. The pyridine adducted complex crystallizes to monoclinic crystal structure, whereas other two adducted complexes have orthorhombic structure. Addition of nitrogen donor ligands enhances the thermal property of these complexes as that with parent metal-organic complex. Zinc acetylacetonate adducted with pyridine shows much higher volatility (106 °C), decomposition temperature (202 °C) as that with zinc acetylacetonate (136 °C, 220 °C), and other adducted complexes. All the adducted complexes are thermally stable, highly volatile and are considered to be suitable precursors for metal organic chemical vapor deposition. The formation of these complexes is confirmed by powder X-ray diffraction, Fourier transform infrared spectroscopy, mass spectroscopy, and elemental analysis. The complexes are widely used as starting precursor materials for the synthesis of ZnO nanostructures by microwave irradiation assisted coating process.

Design and Analysis of a Bio-Inspired Wire-Driven Multi-Section Flexible Robot

OpenAIRE

Li, Zheng; Du, Ruxu

2013-01-01

This paper presents a bio-inspired wire-driven multi-section flexible robot. It is inspired by the snake skeleton and octopus arm muscle arrangements. The robot consists of three sections and each section is made up of several identical vertebras, which are articulated by both spherical joints and a flexible backbone. Each section is driven by two groups of wires, controlling the bending motion in X and Y directions. This design integrates the serpentine robots' structure and the continuum ro...

Kinds of inspiration in interaction design

DEFF Research Database (Denmark)

Halskov, Kim

2010-01-01

In this paper, we explore the role of sources of inspiration in interaction design. We identify four strategies for relating sources of inspiration to emerging ideas: selection; adaptation; translation; and combination. As our starting point, we argue that sources of inspiration are a form...... of knowledge crucial to creativity. Our research is based on empirical findings arising from the use of Inspiration Card Workshops, which are collaborative design events in which domain and technology insight are combined to create design concepts. In addition to the systematically introduced sources...... of inspiration that form part of the workshop format, a number of spontaneous sources of inspiration emerged during these workshops....

Sky light polarization detection with linear polarizer triplet in light field camera inspired by insect vision.

Science.gov (United States)

Zhang, Wenjing; Cao, Yu; Zhang, Xuanzhe; Liu, Zejin

2015-10-20

Stable information of a sky light polarization pattern can be used for navigation with various advantages such as better performance of anti-interference, no "error cumulative effect," and so on. But the existing method of sky light polarization measurement is weak in real-time performance or with a complex system. Inspired by the navigational capability of a Cataglyphis with its compound eyes, we introduce a new approach to acquire the all-sky image under different polarization directions with one camera and without a rotating polarizer, so as to detect the polarization pattern across the full sky in a single snapshot. Our system is based on a handheld light field camera with a wide-angle lens and a triplet linear polarizer placed over its aperture stop. Experimental results agree with the theoretical predictions. Not only real-time detection but simple and costless architecture demonstrates the superiority of the approach proposed in this paper.

Statistical constraints on binary black hole inspiral dynamics

Energy Technology Data Exchange (ETDEWEB)

Galley, Chad R; Herrmann, Frank; Silberholz, John; Tiglio, Manuel [Department of Physics, Center for Fundamental Physics, Center for Scientific Computation and Mathematical Modeling, Joint Space Institute, University of Maryland, College Park, MD 20742 (United States); Guerberoff, Gustavo, E-mail: tiglio@umd.ed [Facultad de IngenierIa, Instituto de Matematica y EstadIstica, ' Prof. Ing. Rafael Laguardia' , Universidad de la Republica, Montevideo (Uruguay)

2010-12-21

We perform a statistical analysis of binary black holes in the post-Newtonian approximation by systematically sampling and evolving the parameter space of initial configurations for quasi-circular inspirals. Through a principal component analysis of spin and orbital angular momentum variables, we systematically look for uncorrelated quantities and find three of them which are highly conserved in a statistical sense, both as functions of time and with respect to variations in initial spin orientations. For example, we find a combination of spin scalar products, 2S-circumflex{sub 1{center_dot}}S-circumflex{sub 2} + (S-circumflex{sub 1{center_dot}}L-circumflex) (S-circumflex{sub 2{center_dot}}L-circumflex), that is exactly conserved in time at the considered post-Newtonian order (including spin-spin and radiative effects) for binaries with equal masses and spin magnitudes evolving in a quasi-circular inspiral. We also look for and find the variables that account for the largest variations in the problem. We present binary black hole simulations of the full Einstein equations analyzing to what extent these results might carry over to the full theory in the inspiral and merger regimes. Among other applications these results should be useful both in semi-analytical and numerical building of templates of gravitational waves for gravitational wave detectors.

Clay Bells: Edo Inspiration

Science.gov (United States)

Wagner, Tom

2010-01-01

The ceremonial copper and iron bells at the Smithsonian's National Museum of African Art were the author's inspiration for an interdisciplinary unit with a focus on the contributions various cultures make toward the richness of a community. The author of this article describes an Edo bell-inspired ceramic project incorporating slab-building…

Bio-inspired computation in telecommunications

CERN Document Server

Yang, Xin-She; Ting, TO

2015-01-01

Bio-inspired computation, especially those based on swarm intelligence, has become increasingly popular in the last decade. Bio-Inspired Computation in Telecommunications reviews the latest developments in bio-inspired computation from both theory and application as they relate to telecommunications and image processing, providing a complete resource that analyzes and discusses the latest and future trends in research directions. Written by recognized experts, this is a must-have guide for researchers, telecommunication engineers, computer scientists and PhD students.

Heart rate asymmetry follows the inspiration/expiration ratio in healthy volunteers

International Nuclear Information System (INIS)

Klintworth, Anne; Ajtay, Zénó; Paljunite, Alina; Szabados, Sándor; Hejjel, László

2012-01-01

Heart rate asymmetry (HRA) quantifies the uneven distribution of points above and below the identity-line in a Poincaré plot of RR-intervals. The authors investigated if HRA could be influenced by the inspiration/expiration ratio. Healthy volunteers (n = 18) were studied in the supine position at 4.5 s metronome breathing. ECG and breathing signals were recorded for 360 s at each breathing pattern: inspiration controlled, inspiration/expiration controlled (1:2, 1:1, 2:1 ratio), inspiration controlled again. Time domain, frequency domain and Poincaré plot heart rate variability (HRV) analysis with Porta's and Guzik's indices were performed on 300 s tachograms. There were no statistically significant differences in time domain, frequency domain and standard Poincaré plot parameters during the various breathing patterns, whereas Porta's and Guzik's indices significantly rose at 1:1 and 2:1 compared to physiological 1:2 breathing. There were no significant differences in the HRA parameters between the first and the last runs. In our population the inspiration/expiration ratio significantly influenced HRA, but not standard HRV parameters. Positive correlation of Guzik's and Porta's index reflects reciprocal changes of the number of points and their dispersion in the accelerating and decelerating sets of RR-intervals. HRA-analysis can be a promising method for investigating cardiovascular regulation/health particularly with further spreading of wearable monitors. (paper)

Structural analysis of protein-ligand interactions: the binding of endogenous compounds and of synthetic drugs.

Science.gov (United States)

Gallina, Anna M; Bork, Peer; Bordo, Domenico

2014-02-01

The large number of macromolecular structures deposited with the Protein Data Bank (PDB) describing complexes between proteins and either physiological compounds or synthetic drugs made it possible a systematic analysis of the interactions occurring between proteins and their ligands. In this work, the binding pockets of about 4000 PDB protein-ligand complexes were investigated and amino acid and interaction types were analyzed. The residues observed with lowest frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the most abundant in binding pockets. Significant differences between drug-like and physiological compounds were found. On average, physiological compounds establish with respect to drugs about twice as many hydrogen bonds with protein atoms, whereas drugs rely more on hydrophobic interactions to establish target selectivity. The large number of PDB structures describing homologous proteins in complex with the same ligand made it possible to analyze the conservation of binding pocket residues among homologous protein structures bound to the same ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than other amino acids. Also in the cases in which the same ligand is bound to unrelated proteins, the binding pockets showed significant conservation in the residue types. In this case, the probability of co-occurrence of the same amino acid type in the binding pockets could be up to thirteen times higher than that expected on a random basis. The trends identified in this study may provide an useful guideline in the process of drug design and lead optimization. Copyright © 2014 John Wiley & Sons, Ltd.

INSPIRE 2012 da Istanbul a Firenze

Directory of Open Access Journals (Sweden)

Mauro Salvemini

2012-09-01

Full Text Available DURING THE CONFERENCE HELD IN  ISTANBUL IN  2012 INSPIRE  THE  NEWS  THAT  MOST  IMPRESSED ITALIANS PRESENT,  EVEN THOSE IN THE PUBLIC ADMINISTRATION , WAS THAT THE NEXT  INSPIRE CONFERENCE WILL TAKE PLACE IN  FLORENCEDurante la conferenza INSPIRE 2012 svoltasi ad Istanbul la notizia che ha maggiormente colpito gli italiani presenti, anche quelli della pubblica amministrazione , è stata che la prossima Conferenza INSPIRE si svolgerà a Firenze dal 23 al 27 giugno 2013.

INSPIRE 2012 da Istanbul a Firenze

Directory of Open Access Journals (Sweden)

Mauro Salvemini

2012-09-01

Full Text Available DURING THE CONFERENCE HELD IN  ISTANBUL IN  2012 INSPIRE  THE  NEWS  THAT  MOST  IMPRESSED ITALIANS PRESENT,  EVEN THOSE IN THE PUBLIC ADMINISTRATION , WAS THAT THE NEXT  INSPIRE CONFERENCE WILL TAKE PLACE IN  FLORENCE Durante la conferenza INSPIRE 2012 svoltasi ad Istanbul la notizia che ha maggiormente colpito gli italiani presenti, anche quelli della pubblica amministrazione , è stata che la prossima Conferenza INSPIRE si svolgerà a Firenze dal 23 al 27 giugno 2013.

Nature-Inspired Structural Materials for Flexible Electronic Devices.

Science.gov (United States)

Liu, Yaqing; He, Ke; Chen, Geng; Leow, Wan Ru; Chen, Xiaodong

2017-10-25

Exciting advancements have been made in the field of flexible electronic devices in the last two decades and will certainly lead to a revolution in peoples' lives in the future. However, because of the poor sustainability of the active materials in complex stress environments, new requirements have been adopted for the construction of flexible devices. Thus, hierarchical architectures in natural materials, which have developed various environment-adapted structures and materials through natural selection, can serve as guides to solve the limitations of materials and engineering techniques. This review covers the smart designs of structural materials inspired by natural materials and their utility in the construction of flexible devices. First, we summarize structural materials that accommodate mechanical deformations, which is the fundamental requirement for flexible devices to work properly in complex environments. Second, we discuss the functionalities of flexible devices induced by nature-inspired structural materials, including mechanical sensing, energy harvesting, physically interacting, and so on. Finally, we provide a perspective on newly developed structural materials and their potential applications in future flexible devices, as well as frontier strategies for biomimetic functions. These analyses and summaries are valuable for a systematic understanding of structural materials in electronic devices and will serve as inspirations for smart designs in flexible electronics.

Correcting binding parameters for interacting ligand-lattice systems

Science.gov (United States)

Hervy, Jordan; Bicout, Dominique J.

2017-07-01

Binding of ligands to macromolecules is central to many functional and regulatory biological processes. Key parameters characterizing ligand-macromolecule interactions are the stoichiometry, inducing the number of ligands per macromolecule binding site, and the dissociation constant, quantifying the ligand-binding site affinity. Both these parameters can be obtained from analyses of classical saturation experiments using the standard binding equation that offers the great advantage of mathematical simplicity but becomes an approximation for situations of interest when a ligand binds and covers more than one single binding site on the macromolecule. Using the framework of car-parking problem with latticelike macromolecules where each ligand can cover simultaneously several consecutive binding sites, we showed that employing the standard analysis leads to underestimation of binding parameters, i.e., ligands appear larger than they actually are and their affinity is also greater than it is. Therefore, we have derived expressions allowing to determine the ligand size and true binding parameters (stoichiometry and dissociation constant) as a function of apparent binding parameters retrieved from standard saturation experiments.

Perceptually-Inspired Computing

Directory of Open Access Journals (Sweden)

Ming Lin

2015-08-01

Full Text Available Human sensory systems allow individuals to see, hear, touch, and interact with the surrounding physical environment. Understanding human perception and its limit enables us to better exploit the psychophysics of human perceptual systems to design more efficient, adaptive algorithms and develop perceptually-inspired computational models. In this talk, I will survey some of recent efforts on perceptually-inspired computing with applications to crowd simulation and multimodal interaction. In particular, I will present data-driven personality modeling based on the results of user studies, example-guided physics-based sound synthesis using auditory perception, as well as perceptually-inspired simplification for multimodal interaction. These perceptually guided principles can be used to accelerating multi-modal interaction and visual computing, thereby creating more natural human-computer interaction and providing more immersive experiences. I will also present their use in interactive applications for entertainment, such as video games, computer animation, and shared social experience. I will conclude by discussing possible future research directions.

Bio-Inspired Optimization of Sustainable Energy Systems: A Review

Directory of Open Access Journals (Sweden)

Yu-Jun Zheng

2013-01-01

Full Text Available Sustainable energy development always involves complex optimization problems of design, planning, and control, which are often computationally difficult for conventional optimization methods. Fortunately, the continuous advances in artificial intelligence have resulted in an increasing number of heuristic optimization methods for effectively handling those complicated problems. Particularly, algorithms that are inspired by the principles of natural biological evolution and/or collective behavior of social colonies have shown a promising performance and are becoming more and more popular nowadays. In this paper we summarize the recent advances in bio-inspired optimization methods, including artificial neural networks, evolutionary algorithms, swarm intelligence, and their hybridizations, which are applied to the field of sustainable energy development. Literature reviewed in this paper shows the current state of the art and discusses the potential future research trends.

Nostalgia-Evoked Inspiration: Mediating Mechanisms and Motivational Implications.

Science.gov (United States)

Stephan, Elena; Sedikides, Constantine; Wildschut, Tim; Cheung, Wing-Yee; Routledge, Clay; Arndt, Jamie

2015-10-01

Six studies examined the nostalgia-inspiration link and its motivational implications. In Study 1, nostalgia proneness was positively associated with inspiration frequency and intensity. In Studies 2 and 3, the recollection of nostalgic (vs. ordinary) experiences increased both general inspiration and specific inspiration to engage in exploratory activities. In Study 4, serial mediational analyses supported a model in which nostalgia increases social connectedness, which subsequently fosters self-esteem, which then boosts inspiration. In Study 5, a rigorous evaluation of this serial mediational model (with a novel nostalgia induction controlling for positive affect) reinforced the idea that nostalgia-elicited social connectedness increases self-esteem, which then heightens inspiration. Study 6 extended the serial mediational model by demonstrating that nostalgia-evoked inspiration predicts goal pursuit (intentions to pursue an important goal). Nostalgia spawns inspiration via social connectedness and attendant self-esteem. In turn, nostalgia-evoked inspiration bolsters motivation. © 2015 by the Society for Personality and Social Psychology, Inc.

Singular instantons in Eddington-inspired-Born-Infeld gravity

Energy Technology Data Exchange (ETDEWEB)

Arroja, Frederico; Chen, Che-Yu; Chen, Pisin; Yeom, Dong-han, E-mail: arroja@phys.ntu.edu.tw, E-mail: b97202056@gmail.com, E-mail: pisinchen@phys.ntu.edu.tw, E-mail: innocent.yeom@gmail.com [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, Taipei, 10617, Taiwan (China)

2017-03-01

In this work, we investigate O (4)-symmetric instantons within the Eddington-inspired-Born-Infeld gravity theory (EiBI) . We discuss the regular Hawking-Moss instanton and find that the tunneling rate reduces to the General Relativity (GR) value, even though the action value is different by a constant. We give a thorough analysis of the singular Vilenkin instanton and the Hawking-Turok instanton with a quadratic scalar field potential in the EiBI theory. In both cases, we find that the singularity can be avoided in the sense that the physical metric, its scalar curvature and the scalar field are regular under some parameter restrictions, but there is a curvature singularity of the auxiliary metric compatible with the connection. We find that the on-shell action is finite and the probability does not reduce to its GR value. We also find that the Vilenkin instanton in the EiBI theory would still cause the instability of the Minkowski space, similar to that in GR, and this is observationally inconsistent. This result suggests that the singularity of the auxiliary metric may be problematic at the quantum level and that these instantons should be excluded from the path integral.

Effect of inspiration on airway dimensions measured in maximal inspiration CT images of subjects without airflow limitation

DEFF Research Database (Denmark)

Petersen, Jens; Wille, Mathilde M.W.; Raket, Lars Lau

2014-01-01

. Automated software was utilized to segment lungs and airways, identify segmental bronchi, and match airway branches in all images of the same subject. Inspiration level was defined as segmented total lung volume (TLV) divided by predicted total lung capacity (pTLC). Mixed-effects models were used to predict......OBJECTIVES: To study the effect of inspiration on airway dimensions measured in voluntary inspiration breath-hold examinations. METHODS: 961 subjects with normal spirometry were selected from the Danish Lung Cancer Screening Trial. Subjects were examined annually for five years with low-dose CT...... • The effect of inspiration is greater in higher-generation (more peripheral) airways • Airways of generation 5 and beyond are as distensible as lung parenchyma • Airway dimensions measured from CT should be adjusted for inspiration level....

Quantitative chemogenomics: machine-learning models of protein-ligand interaction.

Science.gov (United States)

Andersson, Claes R; Gustafsson, Mats G; Strömbergsson, Helena

2011-01-01

Chemogenomics is an emerging interdisciplinary field that lies in the interface of biology, chemistry, and informatics. Most of the currently used drugs are small molecules that interact with proteins. Understanding protein-ligand interaction is therefore central to drug discovery and design. In the subfield of chemogenomics known as proteochemometrics, protein-ligand-interaction models are induced from data matrices that consist of both protein and ligand information along with some experimentally measured variable. The two general aims of this quantitative multi-structure-property-relationship modeling (QMSPR) approach are to exploit sparse/incomplete information sources and to obtain more general models covering larger parts of the protein-ligand space, than traditional approaches that focuses mainly on specific targets or ligands. The data matrices, usually obtained from multiple sparse/incomplete sources, typically contain series of proteins and ligands together with quantitative information about their interactions. A useful model should ideally be easy to interpret and generalize well to new unseen protein-ligand combinations. Resolving this requires sophisticated machine-learning methods for model induction, combined with adequate validation. This review is intended to provide a guide to methods and data sources suitable for this kind of protein-ligand-interaction modeling. An overview of the modeling process is presented including data collection, protein and ligand descriptor computation, data preprocessing, machine-learning-model induction and validation. Concerns and issues specific for each step in this kind of data-driven modeling will be discussed. © 2011 Bentham Science Publishers

Bio-Inspired Design Approach Analysis: A Case Study of Antoni Gaudi and Santiago Calatrava

OpenAIRE

Marzieh Imani

2017-01-01

Antoni Gaudi and Santiago Calatrava have reputation for designing bio-inspired creative and technical buildings. Even though they have followed different independent approaches towards design, the source of bio-inspiration seems to be common. Taking a closer look at their projects reveals that Calatrava has been influenced by Gaudi in terms of interpreting nature and applying natural principles into the design process. This research firstly discusses the dialogue between Biomimicry and archit...

Distribution of the ligand field at the Fe2+ ion in frozen aqueous solutions of Fe(ClO4)2

International Nuclear Information System (INIS)

Nagy, D.L.; Horvath, D.; Szuecs, I.S.; Spiering, H.

1981-01-01

Moessbauer spectra of eutectic frozen aqueous solutions of Fe(ClO 4 ) 2 have been measured at 4.2 K in applied longitudinal magnetic fields up to 5 T. The spectra are interpreted in terms of a model accounting for the random distribution of the ligand field at the Fe 2+ ion owing to the amorphity of the environment. The equilibrium state of the Fe(H 2 O) 6 2+ complex is determined by a static Jahn-Teller calculation. The main features of all spectra can be well reproduced by choosing Esub(JT)(tau)=140 cm -1 and ωsub(tau)=150 cm -1 . (author)

Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

Directory of Open Access Journals (Sweden)

Swati Kaushik

Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

Major advances in the development of histamine H4 receptor ligands.

Science.gov (United States)

Smits, Rogier A; Leurs, Rob; de Esch, Iwan J P

2009-08-01

The search for new and potent histamine H4 receptor ligands is leading to a steadily increasing number of scientific publications and patent applications. Several interesting and structurally diverse compounds have been found, but fierce IP competition for a preferred 2-aminopyrimidine scaffold is becoming apparent. Recent investigations into the role of the histamine H(4)R in (patho)physiology and the use of H4R ligands in in vivo disease models reveal enormous potential in the field of inflammation and allergy, among others. The development of ligands that display activity at two or more histamine receptor (HR) subtypes is another clinical opportunity that is currently being explored. Taken together, the histamine H4R field is gearing up for clinical studies and has the potential to deliver another generation of blockbuster drugs.

Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms.

Directory of Open Access Journals (Sweden)

Mary Lopez-Perez

Full Text Available Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL and the Reticulocyte Binding-Like (PfRh proteins, which are polymorphic and not fully characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1 and five members of the PfRh (PfRh1, PfRh2a, PfRh2b, PfRh4, PfRh5 families were determined. We found that most P. falciparum field isolates from Colombia and Peru invade RBCs through an atypical invasion pathway phenotypically characterized as resistant to all enzyme treatments (NrTrCr. Moreover, the invasion pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant, the PfRh5 variant 1 and EBA-181 RVNKN variant. The ebl and Pfrh expression levels in a field isolate displaying the NrTrCr profile also pointed to PfRh2a, PfRh5 and EBA-181 as being possibly the major players in this invasion pathway. Notably, our studies demonstrate the uniqueness of the Peruvian P. falciparum field isolates in terms of their invasion profiles and ligand polymorphisms, and present a unique opportunity for studying the ability of P. falciparum parasites to expand their invasion repertoire after being reintroduced to human populations. The present study is directly relevant to asexual blood stage vaccine design focused on invasion pathway proteins, suggesting that regional invasion variants and global geographical variation are likely to

Micro+nanotexturing of substrates to enhance ligand-assisted cancer cell isolation

International Nuclear Information System (INIS)

Mahmood, Mohammed Arif I; Islam, Muhymin; Ali, Waqas; Hanif, Madiha; Iqbal, Samir M; Wan, Yuan; Kim, Young-tae

2014-01-01

This paper presents a simple approach to create a two-tiered surface for superior cancer cell isolation. The idea is inspired by the interactions of cells with a nanotextured basement membrane. The texture mimicked the extracellular matrix and basement membrane for superior target cell adhesion. Prepared micro+nanotextured surfaces showed enhanced cell capture. Preparation of the two-tiered surface was done using micro- and nanotexturing and was easily reproducible. It has been shown before that the larger surface area of a nanotextured surface assists the cell’s attachment through surface-anchored ligands. Taking it a step further, ligand functionalized two-level micro+nanotextured surfaces improved the sensitivity of the cancer cell isolation over simple flat nanotexturing. The isolation efficiency increased by 208% compared to the surface with a single-level nanotexture. The two-tiered surface was compatible with previously reported nanotextured devices used for cancer cell isolation. Micro-texture on the glass surface was created using simple sand gritting, followed by reactive ion etching (RIE) of the entire surface. The approach could create large surface areas within a short time while maintaining superior cell isolation efficiency. (paper)

Two novel mixed-ligand complexes containing organosulfonate ligands.

Science.gov (United States)

Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

2008-07-01

The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

Cloud computing approaches for prediction of ligand binding poses and pathways.

Science.gov (United States)

Lawrenz, Morgan; Shukla, Diwakar; Pande, Vijay S

2015-01-22

We describe an innovative protocol for ab initio prediction of ligand crystallographic binding poses and highly effective analysis of large datasets generated for protein-ligand dynamics. We include a procedure for setup and performance of distributed molecular dynamics simulations on cloud computing architectures, a model for efficient analysis of simulation data, and a metric for evaluation of model convergence. We give accurate binding pose predictions for five ligands ranging in affinity from 7 nM to > 200 μM for the immunophilin protein FKBP12, for expedited results in cases where experimental structures are difficult to produce. Our approach goes beyond single, low energy ligand poses to give quantitative kinetic information that can inform protein engineering and ligand design.

SPR-based fragment screening with neurotensin receptor 1 generates novel small molecule ligands

Science.gov (United States)

Huber, Sylwia; Casagrande, Fabio; Hug, Melanie N.; Wang, Lisha; Heine, Philipp; Kummer, Lutz; Plückthun, Andreas; Hennig, Michael

2017-01-01

The neurotensin receptor 1 represents an important drug target involved in various diseases of the central nervous system. So far, the full exploitation of potential therapeutic activities has been compromised by the lack of compounds with favorable physicochemical and pharmacokinetic properties which efficiently penetrate the blood-brain barrier. Recent progress in the generation of stabilized variants of solubilized neurotensin receptor 1 and its subsequent purification and successful structure determination presents a solid starting point to apply the approach of fragment-based screening to extend the chemical space of known neurotensin receptor 1 ligands. In this report, surface plasmon resonance was used as primary method to screen 6369 compounds. Thereby 44 hits were identified and confirmed in competition as well as dose-response experiments. Furthermore, 4 out of 8 selected hits were validated using nuclear magnetic resonance spectroscopy as orthogonal biophysical method. Computational analysis of the compound structures, taking the known crystal structure of the endogenous peptide agonist into consideration, gave insight into the potential fragment-binding location and interactions and inspires chemistry efforts for further exploration of the fragments. PMID:28510609

The influence of ligand field effects on the magnetic exchange of high-spin Co(II)-semiquinonate complexes.

Science.gov (United States)

Bencini, Alessandro; Beni, Alessandra; Costantino, Ferdinando; Dei, Andrea; Gatteschi, Dante; Sorace, Lorenzo

2006-02-07

[Co(Me(4)cyclam)(tropolonate)](PF(6)) was synthesised and structurally characterised. Its electronic and W-band EPR spectra have been analysed by means of the angular overlap calculation of the Spin Hamiltonian parameters that provided also a satisfactory reproduction of the temperature dependence of the magnetic susceptibility. The present results can be interpreted assuming a pseudo-octahedral character for the Co(II) center. This prompted us to reconsider the model formerly used for the analysis of the magnetic coupling between hs-Co(II) and the paramagnetic o-semiquinonate ligand in the corresponding derivatives [Co(Me(4)cyclam)(PhenSQ)](PF(6)) and [Co(Me(4)cyclam)(DTBSQ)](PF(6)). These results indicate that the effect of the magnetic coupling is active only below 50 K and that a more refined model of exchange coupling between Co(II) and semiquinonato ligands is needed to quantitatively analyze the magnetic behaviour of this class of systems.

Ligand field effects in the nuclear magnetic shielding of nitrogen-15 and cobalt-59 in bent nitrosyl complexes of cobalt(III)

International Nuclear Information System (INIS)

Duffin, P.A.; Larkworthy, L.F.; Mason, J.; Stephens, A.N.; Thompson, R.M.

1987-01-01

A range of square-pyramidal complexes of cobalt(III) with a bent apical nitrosyl ligand has been prepared and examined by 15 N and 59 Co NMR spectroscopy, in a study of nephelauxetic and spectrochemical effects at the metal and nitrogen nuclei in the bent Co-NO chromophore. The basal ligands in this comparison include dithiocarbamate, quadridentate Schiff base or porphine, and bis-chelating diamine or oximate, so as to give S 4 , S 2 N 2 , N 4 , OONN, or ONON coordination in the plane and a range of substituents in the chelate and phenylene rings. The shielding of both cobalt and nitrogen tends to decrease with decrease in the M(d) → π*(NO) back-bonding, as indicated by the MN and NO bond distances, the MNO angle and the NO stretching frequency. The shieldings decrease from sulfur to nitrogen to oxygen coligators and also with electron withdrawal by ring substituents (and vice versa), i.e. with decrease in the ligand field splitting and in the nephelauxetism of the coligands. These parallelisms of the cobalt and nitrogen shielding accord with the orbital theory that was developed to explain the bending of the MNO ligand and influences of the metal and coligands. Significant interdependence of spectrochemical and nephelauxetic effects at cobalt and nitrogen arises from the degree of overlap and similarity in energies of the frontier orbitals for the paramagnetic circulation at nitrogen [n(N) → π* (NO)] and at cobalt (d-d). 43 references, 5 figures, 2 tables

Bio-inspired composites with functionally graded platelets exhibit enhanced stiffness.

Science.gov (United States)

Tapse, Sanjay; S, Anup

2017-11-09

Unidirectional composites inspired from biological materials such as nacre, are composed of stiff platelets arranged in a staggered manner within a soft matrix. Elaborate analyses have been conducted on the aforementioned composites and they are found to have excellent mechanical properties like stiffness, strength and fracture toughness. The superior properties exhibited by these composites have been proved to be the result of its unique structure. An emerging development in the field of composite structures is Functionally Graded Composites(FGC), whose properties vary spatially and possess enhanced thermo-mechanical properties. In this paper, the platelets are functionally graded with its Young's Modulus varying parabolically along the length. Two different models - namely, Tension Shear Chain Model and Minimisation of Complementary Energy Model have been employed to obtain the stiffness of the overall composite analytically. The effect of various parameters that define the composite model such as overlapping length between any two neighbouring platelets, different gradation parameters and platelet aspect ratio on the overall mechanical properties have been studied. Composites with functionally graded platelets are found to possess enhanced stiffness (upto 14% higher) for certain values of these parameters. The obtained solutions have been validated using Finite Element Analysis. Bio-inspired composites with functionally graded platelets can be engineered for structural applications, such as in automobile, aerospace and aircraft industry, where stiffness plays a crucial role. © 2017 IOP Publishing Ltd.

La maturità di INSPIRE

Directory of Open Access Journals (Sweden)

Mauro Salvemini

2010-03-01

Full Text Available INPIRE's maturityThe INSPIRE Conference 2010 took place from 23 to 25 June 2010 in Kraków, Poland. On 22 June pre-conference workshops have been organized. The theme of this year’s edition has been "INSPIRE as a Framework for Cooperation".The INSPIRE Conference has been organised through a series of plenary sessions addressing common policy issues, and parallel sessions focusing in particular on applications and implementations of SDIs, research issues and new and evolvingtechnologies and applications and poster presentations.

Biomimetic microsensors inspired by marine life

CERN Document Server

Kottapalli, Ajay Giri Prakash; Miao, Jianmin; Triantafyllou, Michael S

2017-01-01

This book narrates the development of various biomimetic microelectromechanical systems (MEMS) sensors, such as pressure, flow, acceleration, chemical, and tactile sensors, that are inspired by sensing phenomenon that exist in marine life. The research described in this book is multi-faceted and combines the expertise and understanding from diverse fields, including biomimetics, microfabrication, sensor engineering, MEMS design, nanotechnology, and material science. A series of chapters examine the design and fabrication of MEMS sensors that function on piezoresistive, piezoelectric, strain gauge, and chemical sensing principles. By translating nature-based engineering solutions to artificial manmade technology, we could find innovative solutions to critical problems.

AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

Science.gov (United States)

Ravindranath, Pradeep Anand; Sanner, Michel F.

2016-01-01

Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

Non-commutative geometry inspired charged black holes

International Nuclear Information System (INIS)

Ansoldi, Stefano; Nicolini, Piero; Smailagic, Anais; Spallucci, Euro

2007-01-01

We find a new, non-commutative geometry inspired, solution of the coupled Einstein-Maxwell field equations describing a variety of charged, self-gravitating objects, including extremal and non-extremal black holes. The metric smoothly interpolates between de Sitter geometry, at short distance, and Reissner-Nordstrom geometry far away from the origin. Contrary to the ordinary Reissner-Nordstrom spacetime there is no curvature singularity in the origin neither 'naked' nor shielded by horizons. We investigate both Hawking process and pair creation in this new scenario

Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein-Ligand Docking Method.

Science.gov (United States)

Shin, Woong-Hee; Kihara, Daisuke

2018-01-01

Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2 . We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.

Characterization of Colloidal Quantum Dot Ligand Exchange by X-ray Photoelectron Spectroscopy

Science.gov (United States)

Atewologun, Ayomide; Ge, Wangyao; Stiff-Roberts, Adrienne D.

2013-05-01

Colloidal quantum dots (CQDs) are chemically synthesized semiconductor nanoparticles with size-dependent wavelength tunability. Chemical synthesis of CQDs involves the attachment of long organic surface ligands to prevent aggregation; however, these ligands also impede charge transport. Therefore, it is beneficial to exchange longer surface ligands for shorter ones for optoelectronic devices. Typical characterization techniques used to analyze surface ligand exchange include Fourier-transform infrared spectroscopy, x-ray diffraction, transmission electron microscopy, and nuclear magnetic resonance spectroscopy, yet these techniques do not provide a simultaneously direct, quantitative, and sensitive method for evaluating surface ligands on CQDs. In contrast, x-ray photoelectron spectroscopy (XPS) can provide nanoscale sensitivity for quantitative analysis of CQD surface ligand exchange. A unique aspect of this work is that a fingerprint is identified for shorter surface ligands by resolving the regional XPS spectrum corresponding to different types of carbon bonds. In addition, a deposition technique known as resonant infrared matrix-assisted pulsed laser evaporation is used to improve the CQD film uniformity such that stronger XPS signals are obtained, enabling more accurate analysis of the ligand exchange process.

How to deal with multiple binding poses in alchemical relative protein-ligand binding free energy calculations.

Science.gov (United States)

Kaus, Joseph W; Harder, Edward; Lin, Teng; Abel, Robert; McCammon, J Andrew; Wang, Lingle

2015-06-09

Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enhanced sampling methods. In this paper, we apply a previously developed method that provides a corrected binding free energy for ligands with multiple binding modes by combining the free energy results from multiple alchemical FEP calculations starting from all enumerated poses, and the results are compared with Glide docking and MM-GBSA calculations. From these calculations, the dominant ligand binding mode can also be predicted. We apply this method to a series of ligands that bind to c-Jun N-terminal kinase-1 (JNK1) and obtain improved free energy results. The dominant ligand binding modes predicted by this method agree with the available crystallography, while both Glide docking and MM-GBSA calculations incorrectly predict the binding modes for some ligands. The method also helps separate the force field error from the ligand sampling error, such that deviations in the predicted binding free energy from the experimental values likely indicate possible inaccuracies in the force field. An error in the force field for a subset of the ligands studied was identified using this method, and improved free energy results were obtained by correcting the partial charges assigned to the

How To Deal with Multiple Binding Poses in Alchemical Relative Protein–Ligand Binding Free Energy Calculations

Science.gov (United States)

2016-01-01

Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enhanced sampling methods. In this paper, we apply a previously developed method that provides a corrected binding free energy for ligands with multiple binding modes by combining the free energy results from multiple alchemical FEP calculations starting from all enumerated poses, and the results are compared with Glide docking and MM-GBSA calculations. From these calculations, the dominant ligand binding mode can also be predicted. We apply this method to a series of ligands that bind to c-Jun N-terminal kinase-1 (JNK1) and obtain improved free energy results. The dominant ligand binding modes predicted by this method agree with the available crystallography, while both Glide docking and MM-GBSA calculations incorrectly predict the binding modes for some ligands. The method also helps separate the force field error from the ligand sampling error, such that deviations in the predicted binding free energy from the experimental values likely indicate possible inaccuracies in the force field. An error in the force field for a subset of the ligands studied was identified using this method, and improved free energy results were obtained by correcting the partial charges assigned to the

Diphoton resonance in F-theory inspired flipped SO(10)

Energy Technology Data Exchange (ETDEWEB)

Leontaris, George K. [Ioannina University, Physics Department, Theory Division, Ioannina (Greece); Shafi, Qaisar [University of Delaware, Department of Physics and Astronomy, Bartol Research Institute, Newark, DE (United States)

2016-10-15

Motivated by the di-photon excess at 750 GeV reported by the ATLAS and CMS experiments, we present an F-theory inspired flipped SO(10) model embedded in E{sub 6}. The low energy spectrum includes the three MSSM chiral families, vector-like colour triplets, several pairs of charged SU(2){sub L} singlet fields (E{sup c}, anti E{sup c}), as well as MSSM singlets, one or more of which could contribute to the di-photon resonance. A total decay width in the multi-GeV range can arise from couplings involving the singlet and MSSM fields. (orig.)

Norsk inspiration til uddannelse og job

DEFF Research Database (Denmark)

Skovhus, Randi Boelskifte; Thomsen, Rie; Buhl, Rita

2017-01-01

Anmeldelse af bog om det norske fag Utdanningsvalg - inspiration til arbejde med uddannelse og job......Anmeldelse af bog om det norske fag Utdanningsvalg - inspiration til arbejde med uddannelse og job...

Feeling Is Believing: Inspiration Encourages Belief in God.

Science.gov (United States)

Critcher, Clayton R; Lee, Chan Jean

2018-05-01

Even without direct evidence of God's existence, about half of the world's population believes in God. Although previous research has found that people arrive at such beliefs intuitively instead of analytically, relatively little research has aimed to understand what experiences encourage or legitimate theistic belief systems. Using cross-cultural correlational and experimental methods, we investigated whether the experience of inspiration encourages a belief in God. Participants who dispositionally experience more inspiration, were randomly assigned to relive or have an inspirational experience, or reported such experiences to be more inspirational all showed stronger belief in God. These effects were specific to inspiration (instead of adjacent affective experiences) and a belief in God (instead of other empirically unverifiable claims). Being inspired by someone or something (but not inspired to do something) offers a spiritually transcendent experience that elevates belief in God, in part because it makes people feel connected to something beyond themselves.

Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms

DEFF Research Database (Denmark)

Lopez-Perez, Mary; Villasis, Elizabeth; Machado, Ricardo L D

2012-01-01

Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC) invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins, which are polymorphic and not fully...... characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1) and five...... pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant...

Syntheses, X-ray structures, solid state high-field electron paramagnetic resonance, and density-functional theory investigations on chloro and aqua Mn(II) mononuclear complexes with amino-pyridine pentadentate ligands.

Science.gov (United States)

Hureau, Christelle; Groni, Sihem; Guillot, Régis; Blondin, Geneviève; Duboc, Carole; Anxolabéhère-Mallart, Elodie

2008-10-20

The two pentadentate amino-pyridine ligands L5(2) and L5(3) (L5(2) and L5(3) stand for the N-methyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine and the N-methyl-N,N',N'-tris(2-pyridylmethyl)propane-1,3-diamine, respectively) were used to synthesize four mononuclear Mn(II) complexes, namely [(L5(2))MnCl](PF6) (1(PF6)), [(L5(3))MnCl](PF6) (2(PF6)), [(L5(2))Mn(OH2)](BPh4)2 (3(BPh4)2), and [(L5(3))Mn(OH2)](BPh4)2 (4(BPh4)2). The X-ray diffraction studies revealed different configurations for the ligand L5(n) (n = 2, 3) depending on the sixth exogenous ligand and/or the counterion. Solid state high-field electron paramagnetic resonance spectra were recorded on complexes 1-4 as on previously described mononuclear Mn(II) systems with tetra- or hexadentate amino-pyridine ligands. Positive and negative axial zero-field splitting (ZFS) parameters D were determined whose absolute values ranged from 0.090 to 0.180 cm(-1). Density-functional theory calculations were performed unraveling that, in contrast with chloro systems, the spin-spin and spin-orbit coupling contributions to the D-parameter are comparable for mixed N,O-coordination sphere complexes.

Ligand Depot: a data warehouse for ligands bound to macromolecules.

Science.gov (United States)

Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

2004-09-01

Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

Paradigms for biologically inspired design

DEFF Research Database (Denmark)

Lenau, T. A.; Metzea, A.-L.; Hesselberg, T.

2018-01-01

engineering, medical engineering, nanotechnology, photonics,environmental protection and agriculture. However, a major obstacle for the wider use of biologically inspired design isthe knowledge barrier that exist between the application engineers that have insight into how to design suitable productsand......Biologically inspired design is attracting increasing interest since it offers access to a huge biological repository of wellproven design principles that can be used for developing new and innovative products. Biological phenomena can inspireproduct innovation in as diverse areas as mechanical...... the biologists with detailed knowledge and experience in understanding how biological organisms function in theirenvironment. The biologically inspired design process can therefore be approached using different design paradigmsdepending on the dominant opportunities, challenges and knowledge characteristics...

How Agile Methods Inspire Project Management - The Half Double Initiative

DEFF Research Database (Denmark)

Heeager, Lise Tordrup; Svejvig, Per; Schlichter, Bjarne Rerup

Increased complexity in projects has forced new project management initiatives. In software development several agile methods have emerged and are today highly implemented in practice. Observations of general project management practice show how it has been inspired by agile software development......, but very little research addresses the issue of agile project management. In order to understand and to provide suggestions for future practice on how agility can be incorporated in general project management, this paper provides an analysis which compares ten characteristics of agile software development...... (identified in theory) and the Half Double Methodology developed by the Danish Project Half Double initiative; a Methodology developed with practitioners and tested in seven Danish case companies. The analysis shows how the general project management to a great extent has been inspired by agile methods...

Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

Science.gov (United States)

Grüner, Stefan; Neeb, Manuel; Barandun, Luzi Jakob; Sielaff, Frank; Hohn, Christoph; Kojima, Shun; Steinmetzer, Torsten; Diederich, François; Klebe, Gerhard

2014-09-01

The thermodynamic characterization of protein-ligand interactions by isothermal titration calorimetry (ITC) is a powerful tool in drug design, giving valuable insight into the interaction driving forces. ITC is thought to require protein and ligand solutions of high quality, meaning both the absence of contaminants as well as accurately determined concentrations. Ligands synthesized to deviating purity and protein of different pureness were titrated by ITC. Data curation was attempted also considering information from analytical techniques to correct stoichiometry. We used trypsin and tRNA-guanine transglycosylase (TGT), together with high affinity ligands to investigate the effect of errors in protein concentration as well as the impact of ligand impurities on the apparent thermodynamics. We found that errors in protein concentration did not change the thermodynamic properties obtained significantly. However, most ligand impurities led to pronounced changes in binding enthalpy. If protein binding of the respective impurity is not expected, the actual ligand concentration was corrected for and the thus revised data compared to thermodynamic properties obtained with the respective pure ligand. Even in these cases, we observed differences in binding enthalpy of about 4kJ⋅mol(-1), which is considered significant. Our results indicate that ligand purity is the critical parameter to monitor if accurate thermodynamic data of a protein-ligand complex are to be recorded. Furthermore, artificially changing fitting parameters to obtain a sound interaction stoichiometry in the presence of uncharacterized ligand impurities may lead to thermodynamic parameters significantly deviating from the accurate thermodynamic signature. Copyright © 2014 Elsevier B.V. All rights reserved.

Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

Directory of Open Access Journals (Sweden)

Weonu Choe

2016-12-01

Full Text Available The rapidly increasing application of antibodies has inspired the development of several novel methods to isolate and target antibodies using smart biomaterials that mimic the binding of Fc-receptors to antibodies. The Fc-binding domain of antibodies is the primary binding site for e.g., effector proteins and secondary antibodies, whereas antigens bind to the Fab region. Protein A, G, and L, surface proteins expressed by pathogenic bacteria, are well known to bind immunoglobulin and have been widely exploited in antibody purification strategies. Several difficulties are encountered when bacterial proteins are used in antibody research and application. One of the major obstacles hampering the use of bacterial proteins is sample contamination with trace amounts of these proteins, which can invoke an immune response in the host. Many research groups actively develop synthetic ligands that are able to selectively and strongly bind to antibodies. Among the reported ligands, peptides that bind to the Fc-domain of antibodies are attractive tools in antibody research. Besides their use as high affinity ligands in antibody purification chromatography, Fc-binding peptides are applied e.g., to localize antibodies on nanomaterials and to increase the half-life of proteins in serum. In this review, recent developments of Fc-binding peptides are presented and their binding characteristics and diverse applications are discussed.

Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies.

Science.gov (United States)

Bryce, Richard A

2011-04-01

The ability to accurately predict the interaction of a ligand with its receptor is a key limitation in computer-aided drug design approaches such as virtual screening and de novo design. In this article, we examine current strategies for a physics-based approach to scoring of protein-ligand affinity, as well as outlining recent developments in force fields and quantum chemical techniques. We also consider advances in the development and application of simulation-based free energy methods to study protein-ligand interactions. Fuelled by recent advances in computational algorithms and hardware, there is the opportunity for increased integration of physics-based scoring approaches at earlier stages in computationally guided drug discovery. Specifically, we envisage increased use of implicit solvent models and simulation-based scoring methods as tools for computing the affinities of large virtual ligand libraries. Approaches based on end point simulations and reference potentials allow the application of more advanced potential energy functions to prediction of protein-ligand binding affinities. Comprehensive evaluation of polarizable force fields and quantum mechanical (QM)/molecular mechanical and QM methods in scoring of protein-ligand interactions is required, particularly in their ability to address challenging targets such as metalloproteins and other proteins that make highly polar interactions. Finally, we anticipate increasingly quantitative free energy perturbation and thermodynamic integration methods that are practical for optimization of hits obtained from screened ligand libraries.

Histamine H3 receptor ligands in the group of (homo)piperazine derivatives.

Science.gov (United States)

Szczepanska, Katarzyna; Kuder, Kamil; Kiec-Kononowicz, Katarzyna

2017-11-23

Since its' discovery in 1983, followed by gene cloning in 1999, the histamine H3 receptor served as an outstanding target for drug discovery. The wide spectrum of possible therapeutic implications make H3R's one of the most researched areas in the vast GPCR ligands field - started from imidazole containing ligands, through various successful imidazole replacements, with recent introduction of Wakix® to pharmaceutical market. One of such replacements is piperazine moiety, a significant versatile scaffold in rational drug design for most of the GPCR ligands. Therefore, herein we review ligands built on piperazine, as well as its seven membered analogue azepine, that target H3R's and their potential therapeutical applications, in order to elucidate the current state of the art in this vast field. Due to a high level of structural divergence among compounds described herein, we decided to divide them into groups, where the key division element was the position of nitrogen basicity decreasing moieties in (homo)piperazine ring. Paying attention to a number of published structures and their overall high biological activity, one can realize that the (homo)piperazine scaffold bids a versatile template also for histamine H3 receptor ligands. With two possible substitution sites and therefore a number of possible structural combinations, piperazine derivatives stand as one of the largest group of high importance among H3R ligands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

New Ru(II) Complexes for Dual Photoreactivity: Ligand Exchange and 1O2 Generation

OpenAIRE

Knoll, Jessica D.; Albani, Bryan A.; Turro, Claudia

2015-01-01

Uncovering the factors that govern the electronic structure of Ru(II)–polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and 1O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field (3LF) state proceeds through thermal population from the vibrationally cooled triplet meta...

Molecular and electronic structure of chromium(V) nitrido complexes with azide and isothiocyanate ligands

DEFF Research Database (Denmark)

Bendix, Jesper; Birk, Torben; Weyhermüller, Thomas

2005-01-01

. This absorption provides the spectrochemical series for the equatorial ligands, which is found to be numerically almost identical to that determined for chromium(III). DFT calculations reproduce the observed structures and corroborate the ligand field picture of the electronic structure of these complexes....

Origami-inspired active structures: a synthesis and review

International Nuclear Information System (INIS)

Peraza-Hernandez, Edwin A; Hartl, Darren J; Malak Jr, Richard J; Lagoudas, Dimitris C

2014-01-01

Origami, the ancient art of paper folding, has inspired the design of engineering devices and structures for decades. The underlying principles of origami are very general, which has led to applications ranging from cardboard containers to deployable space structures. More recently, researchers have become interested in the use of active materials (i.e., those that convert various forms of energy into mechanical work) to effect the desired folding behavior. When used in a suitable geometry, active materials allow engineers to create self-folding structures. Such structures are capable of performing folding and/or unfolding operations without being kinematically manipulated by external forces or moments. This is advantageous for many applications including space systems, underwater robotics, small scale devices, and self-assembling systems. This article is a survey and analysis of prior work on active self-folding structures as well as methods and tools available for the design of folding structures in general and self-folding structures in particular. The goal is to provide researchers and practitioners with a systematic view of the state-of-the-art in this important and evolving area. Unifying structural principles for active self-folding structures are identified and used as a basis for a quantitative and qualitative comparison of numerous classes of active materials. Design considerations specific to folded structures are examined, including the issues of crease pattern identification and fold kinematics. Although few tools have been created with active materials in mind, many of them are useful in the overall design process for active self-folding structures. Finally, the article concludes with a discussion of open questions for the field of origami-inspired engineering. (topical review)

Cloud computing for protein-ligand binding site comparison.

Science.gov (United States)

Hung, Che-Lun; Hua, Guan-Jie

2013-01-01

The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

Toward automatic regional analysis of pulmonary function using inspiration and expiration thoracic CT

DEFF Research Database (Denmark)

Murphy, Keelin; Pluim, Josien P. W.; Rikxoort, Eva M. van

2012-01-01

and its results; (b) verify that the quantitative, regional ventilation measurements acquired through CT are meaningful for pulmonary function analysis; (c) identify the most effective of the calculated measurements in predicting pulmonary function; and (d) demonstrate the potential of the system...... disorder). Lungs, fissures, airways, lobes, and vessels are automatically segmented in both scans and the expiration scan is registered with the inspiration scan using a fully automatic nonrigid registration algorithm. Segmentations and registrations are examined and scored by expert observers to analyze...... to have good correlation with spirometry results, with several having correlation coefficients, r, in the range of 0.85–0.90. The best performing kNN classifier succeeded in classifying 67% of subjects into the correct COPD GOLD stage, with a further 29% assigned to a class neighboring the correct one...

A biologically inspired artificial fish using flexible matrix composite actuators: analysis and experiment

International Nuclear Information System (INIS)

Zhang, Zhiye; Philen, Michael; Neu, Wayne

2010-01-01

A bio-inspired prototype fish using the flexible matrix composite (FMC) muscle technology for fin and body actuation is developed. FMC actuators are pressure driven muscle-like actuators capable of large displacements as well as large blocking forces. An analytical model of the artificial fish using FMC actuators is developed and analysis results are presented. An experimental prototype of the artificial fish having FMC artificial muscles has been completed and tested. Constant mean thrusts have been achieved in the laboratory for a stationary fish for different undulation frequencies around 1 Hz. The experimental results demonstrate that a nearly constant thrust can be achieved through tuning of excitation frequency for given body stiffness. Free swimming results show that the prototype can swim at approximately 0.3 m s −1

Chemogenomic analysis of G-protein coupled receptors and their ligands deciphers locks and keys governing diverse aspects of signalling.

Directory of Open Access Journals (Sweden)

Jörg D Wichard

Full Text Available Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic or inhibitory (antagonistic ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences.

Guard Cell and Tropomyosin Inspired Chemical Sensor

Directory of Open Access Journals (Sweden)

Jacquelyn K.S. Nagel

2013-10-01

Full Text Available Sensors are an integral part of many engineered products and systems. Biological inspiration has the potential to improve current sensor designs as well as inspire innovative ones. This paper presents the design of an innovative, biologically-inspired chemical sensor that performs “up-front” processing through mechanical means. Inspiration from the physiology (function of the guard cell coupled with the morphology (form and physiology of tropomyosin resulted in two concept variants for the chemical sensor. Applications of the sensor design include environmental monitoring of harmful gases, and a non-invasive approach to detect illnesses including diabetes, liver disease, and cancer on the breath.

Ligand-Free Nanocrystals of Highly Emissive Cs4PbBr6 Perovskite

KAUST Repository

Zhang, Yuhai

2018-02-23

Although ligands of long carbon chains are very crucial to form stable colloidal perovskite nanocrystals (NCs), they create a severe barrier for efficient charge injection or extraction in quantum-dot-based optoelectronics, such as light emitting diode or solar cell. Here, we report a new approach to preparing ligand-free perovskite NCs of CsPbBr, which retained high photoluminescence quantum yield (44%). Such an approach involves a polar solvent (acetonitrile) and two small molecules (ammonium acetate and cesium chloride), which replace the organic ligand and still protect the nanocrystals from dissolution. The successful removal of hydrophobic long ligands was evidenced by Fourier transform infrared spectroscopy, ζ potential analysis, and thermogravimetric analysis. Unlike conventional perovskite NCs that are extremely susceptible to polar solvents, the ligand-free CsPbBr NCs show robust resistance to polar solvents. Our ligand-free procedure opens many possibilities not only from a material hybridization perspective but also in optimizing charge injection and extraction in semiconductor quantum-dot-based optoelectronics applications.

Biologically Inspired Micro-Flight Research

Science.gov (United States)

Raney, David L.; Waszak, Martin R.

2003-01-01

Natural fliers demonstrate a diverse array of flight capabilities, many of which are poorly understood. NASA has established a research project to explore and exploit flight technologies inspired by biological systems. One part of this project focuses on dynamic modeling and control of micro aerial vehicles that incorporate flexible wing structures inspired by natural fliers such as insects, hummingbirds and bats. With a vast number of potential civil and military applications, micro aerial vehicles represent an emerging sector of the aerospace market. This paper describes an ongoing research activity in which mechanization and control concepts for biologically inspired micro aerial vehicles are being explored. Research activities focusing on a flexible fixed- wing micro aerial vehicle design and a flapping-based micro aerial vehicle concept are presented.

Effect of inspiration on airway dimensions measured in maximal inspiration CT images of subjects without airflow limitation

Energy Technology Data Exchange (ETDEWEB)

Petersen, Jens; Raket, Lars Lau; Nielsen, Mads [University of Copenhagen, Department of Computer Science, Copenhagen (Denmark); Wille, Mathilde M.W.; Dirksen, Asger [University of Copenhagen, Department of Respiratory Medicine, Gentofte Hospital, Hellerup (Denmark); Feragen, Aasa [University of Copenhagen, Department of Computer Science, Copenhagen (Denmark); Max Planck Institute for Intelligent Systems and Max Planck Institute for Developmental Biology, Tuebingen (Germany); Pedersen, Jesper H. [Rigshospitalet, University Hospital of Copenhagen, Department of Cardio-Thoracic Surgery RT, Copenhagen (Denmark); Bruijne, Marleen de [University of Copenhagen, Department of Computer Science, Copenhagen (Denmark); Erasmus MC Rotterdam, Departments of Medical Informatics and Radiology, Rotterdam (Netherlands)

2014-09-15

To study the effect of inspiration on airway dimensions measured in voluntary inspiration breath-hold examinations. 961 subjects with normal spirometry were selected from the Danish Lung Cancer Screening Trial. Subjects were examined annually for five years with low-dose CT. Automated software was utilized to segment lungs and airways, identify segmental bronchi, and match airway branches in all images of the same subject. Inspiration level was defined as segmented total lung volume (TLV) divided by predicted total lung capacity (pTLC). Mixed-effects models were used to predict relative change in lumen diameter (ALD) and wall thickness (AWT) in airways of generation 0 (trachea) to 7 and segmental bronchi (R1-R10 and L1-L10) from relative changes in inspiration level. Relative changes in ALD were related to relative changes in TLV/pTLC, and this distensibility increased with generation (p < 0.001). Relative changes in AWT were inversely related to relative changes in TLV/pTLC in generation 3-7 (p < 0.001). Segmental bronchi were widely dispersed in terms of ALD (5.7 ± 0.7 mm), AWT (0.86 ± 0.07 mm), and distensibility (23.5 ± 7.7 %). Subjects who inspire more deeply prior to imaging have larger ALD and smaller AWT. This effect is more pronounced in higher-generation airways. Therefore, adjustment of inspiration level is necessary to accurately assess airway dimensions. (orig.)

Ligand-based design and synthesis of novel sodium channel blockers from a combined phenytoin–lidocaine pharmacophore

OpenAIRE

Wang, Yuesheng; Jones, Paulianda J.; Batts, Timothy W.; Landry, Victoria; Patel, Manoj K.; Brown, Milton L.

2008-01-01

The voltage-gated sodium channel remains a rich area for the development of novel blockers. In this study we used comparative molecular field analysis (CoMFA), a ligand-based design strategy, to generate a 3D model based upon local anesthetics, hydantoins, and α-hydroxyphenylamides to elucidate a SAR for their binding site in the neuronal sodium channel. Correlation by partial least squares (PLS) analysis of in vitro sodium channel binding activity (expressed as pIC50) and the CoMFA descripto...

Ligands in PSI structures

International Nuclear Information System (INIS)

Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

2010-01-01

A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

On gravitational waves in Born-Infeld inspired non-singular cosmologies

Energy Technology Data Exchange (ETDEWEB)

Jiménez, Jose Beltrán [Aix-Marseille Université, Université de Toulon, CNRS, CPT, Marseille (France); Heisenberg, Lavinia [Institute for Theoretical Studies, ETH Zurich, Clausiusstrasse 47, 8092 Zurich (Switzerland); Olmo, Gonzalo J. [Depto. de Física Teórica and IFIC, Universidad de Valencia—CSIC, Calle Dr. Moliner 50, Burjassot 46100, Valencia (Spain); Rubiera-Garcia, Diego, E-mail: jose.beltran@uam.es, E-mail: lavinia.heisenberg@eth-its.ethz.ch, E-mail: gonzalo.olmo@uv.es, E-mail: drgarcia@fc.ul.pt [Instituto de Astrofísica e Ciências do Espaço, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, Campo Grande, P-1749-016 Lisbon (Portugal)

2017-10-01

We study the evolution of gravitational waves for non-singular cosmological solutions within the framework of Born-Infeld inspired gravity theories, with special emphasis on the Eddington-inspired Born-Infeld theory. We review the existence of two types of non-singular cosmologies, namely bouncing and asymptotically Minkowski solutions, from a perspective that makes their features more apparent. We study in detail the propagation of gravitational waves near these non-singular solutions and carefully discuss the origin and severity of the instabilities and strong coupling problems that appear. We also investigate the role of the adiabatic sound speed of the matter sector in the regularisation of the gravitational waves evolution. We extend our analysis to more general Born-Infeld inspired theories where analogous solutions are found. As a general conclusion, we obtain that the bouncing solutions are generally more prone to instabilities, while the asymptotically Minkowski solutions can be rendered stable, making them appealing models for the early universe.

Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans

International Nuclear Information System (INIS)

Kim, Eun Young; Seo, Joon Beom; Lee, Hyun Joo; Kim, Namkug; Lee, Eunsol; Lee, Sang Min; Oh, Sang Young; Hwang, Hye Jeon; Oh, Yeon-Mok; Lee, Sang-Do

2015-01-01

One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas. One hundred and thirty-eight COPD patients and 29 nonsmokers were included in our study. The ATI, the emphysema index (EI), the gas trapping index (Exp -856) and expiration/inspiration ratio of mean lung density (E/Iratio of MLD) were measured on CT. The values of the whole lung, of emphysema, and of hyperinflated and normal lung areas were compared and then correlated with various PFT parameters. Compared with nonsmokers, COPD patients showed a higher ATI in the whole lung and in each lung lesion (all P 25-75% , RV and RV/TLC, and was comparable to Exp -856 and the E/I ratio of MLD. The ATI of emphysema and hyperinflated areas on CT showed better correlation than the normal lung area with PFT parameters. Detailed analysis of density change at inspiration and expiration CT of COPD can provide new insights into pulmonary functional impairment in each lung area. (orig.)

Modelling air quality according to INSPIRE data specifications, ISO standards and national regulations

Directory of Open Access Journals (Sweden)

Pachelski Wojciech

2017-12-01

Full Text Available Protection of the environment is an activity of many institutions, organizations and communities from global to regional and local scales. Any activity in this area needs structured database records, using advanced methodology, given, among others, in INSPIRE documents, ISO standards of 19100 series, and national regulations. The goal of this paper is to analyse both the legal provisions related to the air quality and also data sources associated with the prevention of air pollution. Furthermore, the UML application schema of the spatial data related to the air protection is proposed, for the use by urban planners. Also, the overview of the methodology of geographic information is given, including the Unified Modelling Language (UML, as well as the basic concepts of conceptual models within the INSPIRE project. The study is based on the relevant literature and documents, as well as on the expert knowledge gained through urban planning practice, as well as on the analysis of the spatial planning regulations. The UML application schema for different aspects related to the air protection, as presented in this paper, is an example of how to use the methodology also in other fields of the environment protection. Spatial planners know how to improve the air quality, but in the present state of law they often suffer from the lack of planning tools for real actions. In the spatial planners work an important issue are data that allow a thorough analysis of the area.

An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

KAUST Repository

Ali, Amal J.

2017-05-03

Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

LigParGen web server: an automatic OPLS-AA parameter generator for organic ligands

Science.gov (United States)

Dodda, Leela S.

2017-01-01

Abstract The accurate calculation of protein/nucleic acid–ligand interactions or condensed phase properties by force field-based methods require a precise description of the energetics of intermolecular interactions. Despite the progress made in force fields, small molecule parameterization remains an open problem due to the magnitude of the chemical space; the most critical issue is the estimation of a balanced set of atomic charges with the ability to reproduce experimental properties. The LigParGen web server provides an intuitive interface for generating OPLS-AA/1.14*CM1A(-LBCC) force field parameters for organic ligands, in the formats of commonly used molecular dynamics and Monte Carlo simulation packages. This server has high value for researchers interested in studying any phenomena based on intermolecular interactions with ligands via molecular mechanics simulations. It is free and open to all at jorgensenresearch.com/ligpargen, and has no login requirements. PMID:28444340

Pulling-induced rupture of ligand-receptor bonds between a spherically shaped bionanoparticle and the support

Science.gov (United States)

Zhdanov, Vladimir P.

2018-04-01

Contacts of biological or biologically-inspired spherically shaped nanoparticles (e.g., virions or lipid nanoparticles used for intracellular RNA delivery) with a lipid membrane of cells are often mediated by multiple relatively weak ligand-receptor bonds. Such contacts can be studied at a supported lipid bilayer. The rupture of bonds can be scrutinized by using force spectroscopy. Bearing a supported lipid bilayer in mind, the author shows analytically that the corresponding dependence of the force on the nanoparticle displacement and the effect of the force on the bond-rupture activation energy are qualitatively different compared to what is predicted by the conventional Bell approximation.

Inspiration fra NY-times

DEFF Research Database (Denmark)

Ejersbo, Lisser Rye

2015-01-01

NY-times har en ugentlig klumme med gode råd. For nogle uger siden var ugens inspiration henvendt til lærere/undervisere og drejede sig om, hvordan man skaber taletid til alle uden at have favoritter og overse de mere stille elever.......NY-times har en ugentlig klumme med gode råd. For nogle uger siden var ugens inspiration henvendt til lærere/undervisere og drejede sig om, hvordan man skaber taletid til alle uden at have favoritter og overse de mere stille elever....

An overview of Hofstede-inspired country-level culture research in international business since 2006

NARCIS (Netherlands)

Beugelsdijk, Sjoerd; Kostova, Tatiana; Roth, Kendall

Kirkman, Lowe, & Gibson's (2006) JIBS article summarized and critiqued international business research inspired by the most cited book in the field Hofstede's 1980 Culture's Consequences: International differences in work-related values (Hofstede [1980]2001). They identified a number of issues in

Inspiration til undervisning på museer

DEFF Research Database (Denmark)

Hyllested, Trine Elisabeth

2015-01-01

collection and arrangement of knowledge meant to give a general view of, to inspire and to develop teaching at museums in Denmark......collection and arrangement of knowledge meant to give a general view of, to inspire and to develop teaching at museums in Denmark...

Data specifications for INSPIRE

Science.gov (United States)

Portele, Clemens; Woolf, Andrew; Cox, Simon

2010-05-01

In Europe a major recent development has been the entering in force of the INSPIRE Directive in May 2007, establishing an infrastructure for spatial information in Europe to support Community environmental policies, and policies or activities which may have an impact on the environment. INSPIRE is based on the infrastructures for spatial information established and operated by the 27 Member States of the European Union. The Directive addresses 34 spatial data themes needed for environmental applications, with key components specified through technical implementing rules. This makes INSPIRE a unique example of a legislative "regional" approach. One of the requirements of the INSPIRE Directive is to make existing spatial data sets with relevance for one of the spatial data themes available in an interoperable way, i.e. where the spatial data from different sources in Europe can be combined to a coherent result. Since INSPIRE covers a wide range of spatial data themes, the first step has been the development of a modelling framework that provides a common foundation for all themes. This framework is largely based on the ISO 19100 series of standards. The use of common generic spatial modelling concepts across all themes is an important enabler for interoperability. As a second step, data specifications for the first set of themes has been developed based on the modelling framework. The themes include addresses, transport networks, protected sites, hydrography, administrative areas and others. The data specifications were developed by selected experts nominated by stakeholders from all over Europe. For each theme a working group was established in early 2008 working on their specific theme and collaborating with the other working groups on cross-theme issues. After a public review of the draft specifications starting in December 2008, an open testing process and thorough comment resolution process, the draft technical implementing rules for these themes have been

INSPIRE from the JRC Point of View

Directory of Open Access Journals (Sweden)

Vlado Cetl

2012-12-01

Full Text Available This paper summarises some recent developments in INSPIRE implementation from the JRC (Joint Research Centre point of view. The INSPIRE process started around 11 years ago and today, clear results and benefits can be seen. Spatial data are more accessible and shared more frequently between countries and at the European level. In addition to this, efficient, unified coordination and collaboration between different stakeholders and participants has been achieved, which is another great success. The JRC, as a scientific think-tank of the European Commission, has played a very important role in this process from the very beginning. This role is in line with its mission, which is to provide customer-driven scientific and technical support for the conception, development, implementation and monitoring of European Union (EU policies. The JRC acts as the overall technical coordinator of INSPIRE, but it also carries out the activities necessary to support the coherent implementation of INSPIRE, by helping member states in the implementation process. Experiences drawn from collaboration and negotiation in each country and at the European level will be of great importance in the revision of the INSPIRE Directive, which is envisaged for 2014. Keywords: spatial data infrastructure (SDI; INSPIRE; development; Joint Research Centre (JRC

Nature-inspired computation in engineering

CERN Document Server

2016-01-01

This timely review book summarizes the state-of-the-art developments in nature-inspired optimization algorithms and their applications in engineering. Algorithms and topics include the overview and history of nature-inspired algorithms, discrete firefly algorithm, discrete cuckoo search, plant propagation algorithm, parameter-free bat algorithm, gravitational search, biogeography-based algorithm, differential evolution, particle swarm optimization and others. Applications include vehicle routing, swarming robots, discrete and combinatorial optimization, clustering of wireless sensor networks, cell formation, economic load dispatch, metamodeling, surrogated-assisted cooperative co-evolution, data fitting and reverse engineering as well as other case studies in engineering. This book will be an ideal reference for researchers, lecturers, graduates and engineers who are interested in nature-inspired computation, artificial intelligence and computational intelligence. It can also serve as a reference for relevant...

Investigation of formation constant of complex of a new synthesized tripodal ligand with Cu2+ using rank annihilation factor analysis in surfactant media

Directory of Open Access Journals (Sweden)

R. Golbedaghi

2014-01-01

Full Text Available The complex formation between a newly synthesized tripodal ligand and the cation Cu2+ in water and surfactant media was studied spectrophotometrically using rank annihilation factor analysis (RAFA. According to molar ratio data the stoichiometry of complexation between the ligand and the cation Cu2+ was 1:1. Formation constant of this complex was derived using RAFA on spectrophotometric data. The performance of the method has been evaluated by using synthetic data. Also concentration and spectral profiles of ligand and complex can be obtained by using the stability constant and appropriate equations. The effect of surfactants such as sodium dodecyl sulfate (SDS, cetyltrimethylammonium bromide (CTAB and Triton X-100 on complex formation constant of Cu2+ with the ligand was investigated.

Role of ligand-ligand vs. core-core interactions in gold nanoclusters.

Science.gov (United States)

Milowska, Karolina Z; Stolarczyk, Jacek K

2016-05-14

The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.

Development and evaluation of the INSPIRE measure of staff support for personal recovery.

Science.gov (United States)

Williams, Julie; Leamy, Mary; Bird, Victoria; Le Boutillier, Clair; Norton, Sam; Pesola, Francesca; Slade, Mike

2015-05-01

No individualised standardised measure of staff support for mental health recovery exists. To develop and evaluate a measure of staff support for recovery. initial draft of measure based on systematic review of recovery processes; consultation (n = 61); and piloting (n = 20). Psychometric evaluation: three rounds of data collection from mental health service users (n = 92). INSPIRE has two sub-scales. The 20-item Support sub-scale has convergent validity (0.60) and adequate sensitivity to change. Exploratory factor analysis (variance 71.4-85.1 %, Kaiser-Meyer-Olkin 0.65-0.78) and internal consistency (range 0.82-0.85) indicate each recovery domain is adequately assessed. The 7-item Relationship sub-scale has convergent validity 0.69, test-retest reliability 0.75, internal consistency 0.89, a one-factor solution (variance 70.5 %, KMO 0.84) and adequate sensitivity to change. A 5-item Brief INSPIRE was also evaluated. INSPIRE and Brief INSPIRE demonstrate adequate psychometric properties, and can be recommended for research and clinical use.

Effects of barefoot and barefoot inspired footwear on knee and ankle loading during running.

Science.gov (United States)

Sinclair, Jonathan

2014-04-01

Recreational runners frequently suffer from chronic pathologies. The knee and ankle have been highlighted as common injury sites. Barefoot and barefoot inspired footwear have been cited as treatment modalities for running injuries as opposed to more conventional running shoes. This investigation examined knee and ankle loading in barefoot and barefoot inspired footwear in relation to conventional running shoes. Thirty recreational male runners underwent 3D running analysis at 4.0m·s(-1). Joint moments, patellofemoral contact force and pressure and Achilles tendon forces were compared between footwear. At the knee the results show that barefoot and barefoot inspired footwear were associated with significant reductions in patellofemoral kinetic parameters. The ankle kinetics indicate that barefoot and barefoot inspired footwear were associated with significant increases in Achilles tendon force compared to conventional shoes. Barefoot and barefoot inspired footwear may serve to reduce the incidence of knee injuries in runners although corresponding increases in Achilles tendon loading may induce an injury risk at this tendon. Copyright © 2014 Elsevier Ltd. All rights reserved.

Design, Testing and Kinetic Analysis of Bulky Monodentate Phosphorus Ligands in the Mizoroki-Heck Reaction

NARCIS (Netherlands)

Dodds, Deborah L.; Boele, Maarten D. K.; van Strijdonck, Gino P. F.; de Vries, Johannes G.; van Leeuwen, Piet W. N. M.; Kamer, Paul C. J.

A series of new monodentate phosphane ligands 2 have been evaluated in the MizorokiHeck arylation reaction of iodobenzene and styrene and compared with our previously reported ligands, 1, 3 and 4. The concept of rational ligand design is discussed, and we describe how the performance of this new

[Nikola Tesla: flashes of inspiration].

Science.gov (United States)

Villarejo-Galende, Albero; Herrero-San Martín, Alejandro

2013-01-16

Nikola Tesla (1856-1943) was one of the greatest inventors in history and a key player in the revolution that led to the large-scale use of electricity. He also made important contributions to such diverse fields as x-rays, remote control, radio, the theory of consciousness or electromagnetism. In his honour, the international unit of magnetic induction was named after him. Yet, his fame is scarce in comparison with that of other inventors of the time, such as Edison, with whom he had several heated arguments. He was a rather odd, reserved person who lived for his inventions, the ideas for which came to him in moments of inspiration. In his autobiography he relates these flashes with a number of neuropsychiatric manifestations, which can be seen to include migraine auras, synaesthesiae, obsessions and compulsions.

Accretion onto a noncommutative geometry inspired black hole

Energy Technology Data Exchange (ETDEWEB)

Kumar, Rahul [Jamia Millia Islamia, Centre for Theoretical Physics, New Delhi (India); Ghosh, Sushant G. [Jamia Millia Islamia, Centre for Theoretical Physics, New Delhi (India); Jamia Millia Islamia, Multidisciplinary Centre for Advanced Research and Studies (MCARS), New Delhi (India); University of KwaZulu-Natal, Astrophysics and Cosmology Research Unit, School of Mathematics, Statistics and Computer Science, Durban (South Africa)

2017-09-15

The spherically symmetric accretion onto a noncommutative (NC) inspired Schwarzschild black hole is treated for a polytropic fluid. The critical accretion rate M, sonic speed a{sub s} and other flow parameters are generalized for the NC inspired static black hole and compared with the results obtained for the standard Schwarzschild black holes. Also explicit expressions for gas compression ratios and temperature profiles below the accretion radius and at the event horizon are derived. This analysis is a generalization of Michel's solution to the NC geometry. Owing to the NC corrected black hole, the accretion flow parameters also have been modified. It turns out that M ∼ M{sup 2} is still achievable but r{sub s} seems to be substantially decreased due to the NC effects. They in turn do affect the accretion process. (orig.)

Inspiring Careers in STEM and Healthcare Fields through Medical Simulation Embedded in High School Science Education

Science.gov (United States)

Berk, Louis J.; Muret-Wagstaff, Sharon L.; Goyal, Riya; Joyal, Julie A.; Gordon, James A.; Faux, Russell; Oriol, Nancy E.

2014-01-01

The most effective ways to promote learning and inspire careers related to science, technology, engineering, and mathematics (STEM) remain elusive. To address this gap, we reviewed the literature and designed and implemented a high-fidelity, medical simulation-based Harvard Medical School MEDscience course, which was integrated into high school…

Template synthesis, characterization and antimicrobial activity of some new complexes with isonicotinoyl hydrazone ligands

Directory of Open Access Journals (Sweden)

LIVIU MITU

2009-09-01

Full Text Available Complexes of Cu(II, Ni(II, Co(II with the 9-anthraldehyde iso-nicotinoyl hydrazone ligand (HL1 and the 3,5-di-tert-butyl-4-hydroxy-benzaldehyde isonicotinoyl hydrazone ligand (H2L2 were synthesized by the template method. The complexes were characterized by analytical analysis, IR, UV-Vis and ESR spectroscopy, magnetic measurements, conductometry and thermal analysis and the two ligands by 1H-NMR spectroscopy. From the elemental analysis, 1:2 (metal:ligand stoichiometry for the complexes of Cu(II, Ni(II with the ligands HL1 and H2L2 and 1:1 (metal:ligand stoichiometry for the complex of Co(II with the ligand HL1 are proposed. The molar conductance data showed that the complexes are non-electrolytes. The magnetic susceptibility results coupled with the electronic and ESR spectra suggested a distorted octahedral geometry for the complexes Ni(II/HL1, Ni(II/H2L2 and Cu(II/H2L2, a tetrahedral stereochemistry for the complex Cu/HL1 and a square-planar geometry for the complex Co/HL1. The IR spectra demonstrated the bidentate coordination of the ligands HL1 and H2L2 by the O=C amide oxygen and the azomethine nitrogen, as well as monodentate coordination of the ligand HL1 by the azomethine nitrogen in the Cu(IIcomplex. The antibacterial activity of the ligands and their metallic complexes were tested against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae.

Creating identity with nature inspired lighting design – The Sensitive Organism

Directory of Open Access Journals (Sweden)

Hiort-Lorenzen Anna-Rosa

2018-01-01

Full Text Available People, as living organisms, exist in symbiosis with nature; therefore, contact with nature is a basic human need. City nature is an important aspect of the urban living environment because people need an escapist experience from the everyday city life that they should find within their close environment. The outdoor lighting of urban nightscapes has a major influence on people's perception of space. Cities with an increasing number of inhabitants and late-night economic activity transform into 24-hour operating cities. This means that more attention should be given to investigating the social needs of public spaces in terms of night-time urban lighting, creating experiences and identities with nature. This paper aims to emphasize the potential hidden in nature-inspired lighting as a topic for further development in the field of lighting design. Nature inspired lighting is based on a transdisciplinary approach, where terms like biomimicry, biophilia, and urban green space adopted from other subject fields than lighting influence the lighting design process in order to create a product addressing human inner connectedness to nature. The example used in this paper presents the concept of a lighting master plan called “The Sensitive Organism”.

Tunable axial gauge fields in engineered Weyl semimetals: semiclassical analysis and optical lattice implementations

Science.gov (United States)

Roy, Sthitadhi; Kolodrubetz, Michael; Goldman, Nathan; Grushin, Adolfo G.

2018-04-01

In this work, we describe a toolbox to realize and probe synthetic axial gauge fields in engineered Weyl semimetals. These synthetic electromagnetic fields, which are sensitive to the chirality associated with Weyl nodes, emerge due to spatially and temporally dependent shifts of the corresponding Weyl momenta. First, we introduce two realistic models, inspired by recent cold-atom developments, which are particularly suitable for the exploration of these synthetic axial gauge fields. Second, we describe how to realize and measure the effects of such axial fields through center-of-mass observables, based on semiclassical equations of motion and exact numerical simulations. In particular, we suggest realistic protocols to reveal an axial Hall response due to the axial electric field \

Natural bond orbital analysis of molecular interactions: Theoretical study of W(CO)5 complexes with E(PH3)2 and NHEMe ligands (E=C, Si, Ge, Sn, Pb)

International Nuclear Information System (INIS)

Nguyen Thi Ai Nhung; Huynh Thi Phuong Loan; Duong Tuan Quang; Pham Van Tat

2014-01-01

The complexes with ligands carbodiphosphorane-analogues (called tetrylones) [(CO) 5 W-{E(PH 3 ) 2 }] (W5-EP 2 ) and N-heterocyclic carbene-analogues (called tetrylenes) [(CO) 5 W-{NHE Me }] (W5-NHE Me ) when E=C-Pb have been studied using natural bond orbital (NBO) method. The NBO analysis provides a consistent picture of the chemical bonding is two entire families of transition metal complexes of tetrylone and tetrylene ligands in term of donor-acceptor interactions, showing the correlation of these interactions with Wiberg bond indies (WBI), natural partial charges, and the energetically highest lying occupied molecular orbitals for σ and π orbitals of free ligands E(PH 3 ) 2 and NHE Me . Analysis of the bonding situation reveals that in E(PH 3 ) 2 and NHE Me ligands, the energy level of the π orbital rises, whereas that of the σ orbital decreases as atom E becomes heavier. The complexes with head-on-bonded ligands have (CO) 5 W←E donation which comes from the σ-lone-pair orbital of E(PH 3 ) 2 and NHE Me where E=C for tetrylones and E=C, Si, Ge for tetrylenes, whereas the (CO) 5 W←E donation in the side-on bonded complexes when E becomes heavier arises from the π-lone-pair orbital of E(PH 3 ) 2 and NHE Me ligands which is the HOMO of the free ligands. This makes the heavier adducts of tetrylones and tetrylenes become stronger donors than the lighter systems. The NBO analysis suggests that the E(PH 3 ) 2 ligands are strong σ-donors and strong π-acceptors while the NHE Me ligands are strong σ-donors and weak π-acceptors. This is possible for tetrylones that have two lone-pair orbitals available for donation, whereas the tetrylenes have only one lone-pair orbital available for donation. (author)

AFAL: a web service for profiling amino acids surrounding ligands in proteins

Science.gov (United States)

Arenas-Salinas, Mauricio; Ortega-Salazar, Samuel; Gonzales-Nilo, Fernando; Pohl, Ehmke; Holmes, David S.; Quatrini, Raquel

2014-11-01

With advancements in crystallographic technology and the increasing wealth of information populating structural databases, there is an increasing need for prediction tools based on spatial information that will support the characterization of proteins and protein-ligand interactions. Herein, a new web service is presented termed amino acid frequency around ligand (AFAL) for determining amino acids type and frequencies surrounding ligands within proteins deposited in the Protein Data Bank and for assessing the atoms and atom-ligand distances involved in each interaction (availability: http://structuralbio.utalca.cl/AFAL/index.html). AFAL allows the user to define a wide variety of filtering criteria (protein family, source organism, resolution, sequence redundancy and distance) in order to uncover trends and evolutionary differences in amino acid preferences that define interactions with particular ligands. Results obtained from AFAL provide valuable statistical information about amino acids that may be responsible for establishing particular ligand-protein interactions. The analysis will enable investigators to compare ligand-binding sites of different proteins and to uncover general as well as specific interaction patterns from existing data. Such patterns can be used subsequently to predict ligand binding in proteins that currently have no structural information and to refine the interpretation of existing protein models. The application of AFAL is illustrated by the analysis of proteins interacting with adenosine-5'-triphosphate.

Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans

Energy Technology Data Exchange (ETDEWEB)

Kim, Eun Young [Chonbuk National University Medical School and Hospital, Research Institute of Clinical Medicine, Department of Radiology, Jeollabuk-do (Korea, Republic of); University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Seo, Joon Beom; Lee, Hyun Joo; Kim, Namkug; Lee, Eunsol; Lee, Sang Min; Oh, Sang Young [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Hwang, Hye Jeon [Hallym University Sacred Heart Hospital, Department of Radiology, Hallym University College of Medicine, Gyeonggi-do (Korea, Republic of); Oh, Yeon-Mok; Lee, Sang-Do [University of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Seoul (Korea, Republic of)

2014-09-14

One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas. One hundred and thirty-eight COPD patients and 29 nonsmokers were included in our study. The ATI, the emphysema index (EI), the gas trapping index (Exp -856) and expiration/inspiration ratio of mean lung density (E/Iratio of MLD) were measured on CT. The values of the whole lung, of emphysema, and of hyperinflated and normal lung areas were compared and then correlated with various PFT parameters. Compared with nonsmokers, COPD patients showed a higher ATI in the whole lung and in each lung lesion (all P < 0.05). The ATI showed a higher correlation than EI with FEF{sub 25-75%}, RV and RV/TLC, and was comparable to Exp -856 and the E/I ratio of MLD. The ATI of emphysema and hyperinflated areas on CT showed better correlation than the normal lung area with PFT parameters. Detailed analysis of density change at inspiration and expiration CT of COPD can provide new insights into pulmonary functional impairment in each lung area. (orig.)

Fast and Efficient Fragment-Based Lead Generation by Fully Automated Processing and Analysis of Ligand-Observed NMR Binding Data.

Science.gov (United States)

Peng, Chen; Frommlet, Alexandra; Perez, Manuel; Cobas, Carlos; Blechschmidt, Anke; Dominguez, Santiago; Lingel, Andreas

2016-04-14

NMR binding assays are routinely applied in hit finding and validation during early stages of drug discovery, particularly for fragment-based lead generation. To this end, compound libraries are screened by ligand-observed NMR experiments such as STD, T1ρ, and CPMG to identify molecules interacting with a target. The analysis of a high number of complex spectra is performed largely manually and therefore represents a limiting step in hit generation campaigns. Here we report a novel integrated computational procedure that processes and analyzes ligand-observed proton and fluorine NMR binding data in a fully automated fashion. A performance evaluation comparing automated and manual analysis results on (19)F- and (1)H-detected data sets shows that the program delivers robust, high-confidence hit lists in a fraction of the time needed for manual analysis and greatly facilitates visual inspection of the associated NMR spectra. These features enable considerably higher throughput, the assessment of larger libraries, and shorter turn-around times.

LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

KAUST Repository

Chen, Peng

2014-12-03

Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

The Inspiring Science Education project and the resources for HEP analysis by university students

International Nuclear Information System (INIS)

Fassouliotis, Dimitris; Kourkoumelis, Christine; Vourakis, Stylianos

2016-01-01

The Inspiring Science Education outreach project has been running for more than two years, creating a large number of inquiry based educational resources for high-school teachers and students. Its goal is the promotion of science education in schools though new methods built on the inquiry based education techniques, involving large consortia of European partners and implementation of large-scale pilots in schools. Recent hands-on activities, developing and testing the above mentioned innovative applications are reviewed. In general, there is a lack for educational scenaria and laboratory courses earmarked for more advanced, namely university, students. At the University of Athens for the last four years, the HYPATIA on-line event analysis tool has been used as a lab course for fourth year undergraduate physics students, majoring in HEP. Up to now, the course was limited to visual inspection of a few tens of ATLAS events. Recently the course was enriched with additional analysis exercises, which involve large samples of events. The students through a user friendly interface can analyse the samples and optimize the cut selection in order to search for new physics. The implementation of this analysis is described

Inspiration, anyone? (Editorial

Directory of Open Access Journals (Sweden)

Lindsay Glynn

2006-09-01

Full Text Available I have to admit that writing an editorial for this issue was a struggle. Trying to sit down and write when the sun was shining outside and most of my colleagues were on vacation was, to say the least, difficult. Add to that research projects and conferences…let’s just say that I found myself less than inspired. A pitiful plea for ideas to a colleague resulted in the reintroduction to a few recent evidence based papers and resources which inspired further searching and reading. Though I generally find myself surrounded (more like buried in research papers and EBLIP literature, somehow I had missed the great strides that have been made of late in the world of evidence based library and information practice. I realize now that I am inspired by the researchers, authors and innovators who are putting EBLIP on the proverbial map. My biggest beef with library literature in general has been the plethora of articles highlighting what we should be doing. Take a close look at the evidence based practitioners in the information professions: these are some of the people who are actively practicing what has been preached for the past few years. Take, for example, the about‐to‐be released Libraries using Evidence Toolkit by Northern Sydney Central Coast Health and The University of Newcastle, Australia (see their announcement in this issue. An impressive advisory group is responsible for maintaining the currency and relevancy of the site as well as promoting the site and acting as a steering committee for related projects. This group is certainly doing more than “talking the talk”: they took their experience at the 3rd International Evidence Based Librarianship Conference and did something with the information they obtained by implementing solutions that worked in their environment. The result? The creation of a collection of tools for all of us to use. This toolkit is just what EBLIP needs: a portal to resources aimed at supporting the information

A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.

Science.gov (United States)

Poznański, Jarosław; Poznańska, Anna; Shugar, David

2014-01-01

Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.

Computational speech segregation based on an auditory-inspired modulation analysis

DEFF Research Database (Denmark)

May, Tobias; Dau, Torsten

2014-01-01

A monaural speech segregation system is presented that estimates the ideal binary mask from noisy speech based on the supervised learning of amplitude modulation spectrogram (AMS) features. Instead of using linearly scaled modulation filters with constant absolute bandwidth, an auditory- inspired...... about speech activity present in neighboring time-frequency units. In order to evaluate the generalization performance of the system to unseen acoustic conditions, the speech segregation system is trained with a limited set of low signal-to-noise ratio (SNR) conditions, but tested over a wide range...

Biologically Inspired Technology Using Electroactive Polymers (EAP)

Science.gov (United States)

Bar-Cohen, Yoseph

2006-01-01

Evolution allowed nature to introduce highly effective biological mechanisms that are incredible inspiration for innovation. Humans have always made efforts to imitate nature's inventions and we are increasingly making advances that it becomes significantly easier to imitate, copy, and adapt biological methods, processes and systems. This brought us to the ability to create technology that is far beyond the simple mimicking of nature. Having better tools to understand and to implement nature's principles we are now equipped like never before to be inspired by nature and to employ our tools in far superior ways. Effectively, by bio-inspiration we can have a better view and value of nature capability while studying its models to learn what can be extracted, copied or adapted. Using electroactive polymers (EAP) as artificial muscles is adding an important element to the development of biologically inspired technologies.

Crystallization of protein–ligand complexes

International Nuclear Information System (INIS)

Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

2007-01-01

Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

Performance Characteristics of Bio-Inspired Metal Nanostructures as Surface-Enhanced Raman Scattered (SERS) Substrates.

Science.gov (United States)

Areizaga-Martinez, Hector I; Kravchenko, Ivan; Lavrik, Nickolay V; Sepaniak, Michael J; Hernández-Rivera, Samuel P; De Jesús, Marco A

2016-09-01

The fabrication of high-performance plasmonic nanomaterials for bio-sensing and trace chemical detection is a field of intense theoretical and experimental research. The use of metal-silicon nanopillar arrays as analytical sensors has been reported with reasonable results in recent years. The use of bio-inspired nanocomposite structures that follow the Fibonacci numerical architecture offers the opportunity to develop nanostructures with theoretically higher and more reproducible plasmonic fields over extended areas. The work presented here describes the nanofabrication process for a series of 40 µm × 40 µm bio-inspired arrays classified as asymmetric fractals (sunflower seeds and romanesco broccoli), bilaterally symmetric (acacia leaves and honeycombs), and radially symmetric (such as orchids and lily flowers) using electron beam lithography. In addition, analytical capabilities were evaluated using surface-enhanced Raman scattering (SERS). The substrate characterization and SERS performance of the developed substrates as the strategies to assess the design performance are presented and discussed. © The Author(s) 2016.

Nanofluidics in two-dimensional layered materials: inspirations from nature.

Science.gov (United States)

Gao, Jun; Feng, Yaping; Guo, Wei; Jiang, Lei

2017-08-29

With the advance of chemistry, materials science, and nanotechnology, significant progress has been achieved in the design and application of synthetic nanofluidic devices and materials, mimicking the gating, rectifying, and adaptive functions of biological ion channels. Fundamental physics and chemistry behind these novel transport phenomena on the nanoscale have been explored in depth on single-pore platforms. However, toward real-world applications, one major challenge is to extrapolate these single-pore devices into macroscopic materials. Recently, inspired partially by the layered microstructure of nacre, the material design and large-scale integration of artificial nanofluidic devices have stepped into a completely new stage, termed 2D nanofluidics. Unique advantages of the 2D layered materials have been found, such as facile and scalable fabrication, high flux, efficient chemical modification, tunable channel size, etc. These features enable wide applications in, for example, biomimetic ion transport manipulation, molecular sieving, water treatment, and nanofluidic energy conversion and storage. This review highlights the recent progress, current challenges, and future perspectives in this emerging research field of "2D nanofluidics", with emphasis on the thought of bio-inspiration.

Sum-of-squares-based fuzzy controller design using quantum-inspired evolutionary algorithm

Science.gov (United States)

Yu, Gwo-Ruey; Huang, Yu-Chia; Cheng, Chih-Yung

2016-07-01

In the field of fuzzy control, control gains are obtained by solving stabilisation conditions in linear-matrix-inequality-based Takagi-Sugeno fuzzy control method and sum-of-squares-based polynomial fuzzy control method. However, the optimal performance requirements are not considered under those stabilisation conditions. In order to handle specific performance problems, this paper proposes a novel design procedure with regard to polynomial fuzzy controllers using quantum-inspired evolutionary algorithms. The first contribution of this paper is a combination of polynomial fuzzy control and quantum-inspired evolutionary algorithms to undertake an optimal performance controller design. The second contribution is the proposed stability condition derived from the polynomial Lyapunov function. The proposed design approach is dissimilar to the traditional approach, in which control gains are obtained by solving the stabilisation conditions. The first step of the controller design uses the quantum-inspired evolutionary algorithms to determine the control gains with the best performance. Then, the stability of the closed-loop system is analysed under the proposed stability conditions. To illustrate effectiveness and validity, the problem of balancing and the up-swing of an inverted pendulum on a cart is used.

Ionophoretic method in the study of mixed ligand ternary chelates of UO2(II), Ni(II) and Zn(II) involving nitrilotriacetate and cytosine as ligands

International Nuclear Information System (INIS)

Mishra, A.P.; Mishra, S.K.; Yadava, K.L.

1987-01-01

A novel electrophoretic technique is described for the assessment of the equilibria in mixed-ligand complex system in solution. It is based on the movement of spot of the metal ion under an electric field with the complexants added in the background electrolyte at fixed pH. The concentration of primary ligand nitrilotriacetate was constant while that of secondary ligand (cytosine) was varied. The plot of log (cytosine) against mobility was used to obtain information on the formation of the mixed complexes and to calculate its stability constants. Experimentally obtained logK values are as 5.62, 4.55 and 4.42 for mixed complexes of UO 2 (II), Ni(II) and Zn(II) respectively at μ=0.1 and temp.=35 +- 01.degC. (author). 10 refs

A Bio-Inspired QoS-Oriented Handover Model in Heterogeneous Wireless Networks

Directory of Open Access Journals (Sweden)

Daxin Tian

2014-01-01

Full Text Available We propose a bio-inspired model for making handover decision in heterogeneous wireless networks. It is based on an extended attractor selection model, which is biologically inspired by the self-adaptability and robustness of cellular response to the changes in dynamic environments. The goal of the proposed model is to guarantee multiple terminals’ satisfaction by meeting the QoS requirements of those terminals’ applications, and this model also attempts to ensure the fairness of network resources allocation, in the meanwhile, to enable the QoS-oriented handover decision adaptive to dynamic wireless environments. Some numerical simulations are preformed to validate our proposed bio-inspired model in terms of adaptive attractor selection in different noisy environments. And the results of some other simulations prove that the proposed handover scheme can adapt terminals’ network selection to the varying wireless environment and benefits the QoS of multiple terminal applications simultaneously and automatically. Furthermore, the comparative analysis also shows that the bio-inspired model outperforms the utility function based handover decision scheme in terms of ensuring a better QoS satisfaction and a better fairness of network resources allocation in dynamic heterogeneous wireless networks.

Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a.

Directory of Open Access Journals (Sweden)

Keith A Hultman

2007-01-01

Full Text Available The retention of particular genes after the whole genome duplication in zebrafish has given insights into how genes may evolve through partitioning of ancestral functions. We examine the partitioning of expression patterns and functions of two zebrafish kit ligands, kit ligand a (kitla and kit ligand b (kitlb, and discuss their possible coevolution with the duplicated zebrafish kit receptors (kita and kitb. In situ hybridizations show that kitla mRNA is expressed in the trunk adjacent to the notochord in the middle of each somite during stages of melanocyte migration and later expressed in the skin, when the receptor is required for melanocyte survival. kitla is also expressed in other regions complementary to kita receptor expression, including the pineal gland, tail bud, and ear. In contrast, kitlb mRNA is expressed in brain ventricles, ear, and cardinal vein plexus, in regions generally not complementary to either zebrafish kit receptor ortholog. However, like kitla, kitlb is expressed in the skin during stages consistent with melanocyte survival. Thus, it appears that kita and kitla have maintained congruent expression patterns, while kitb and kitlb have evolved divergent expression patterns. We demonstrate the interaction of kita and kitla by morpholino knockdown analysis. kitla morphants, but not kitlb morphants, phenocopy the null allele of kita, with defects for both melanocyte migration and survival. Furthermore, kitla morpholino, but not kitlb morpholino, interacts genetically with a sensitized allele of kita, confirming that kitla is the functional ligand to kita. Last, we examine kitla overexpression in embryos, which results in hyperpigmentation caused by an increase in the number and size of melanocytes. This hyperpigmentation is dependent on kita function. We conclude that following genome duplication, kita and kitla have maintained their receptor-ligand relationship, coevolved complementary expression patterns, and that

Geonic black holes and remnants in Eddington-inspired Born-Infeld gravity.

Science.gov (United States)

Olmo, Gonzalo J; Rubiera-Garcia, D; Sanchis-Alepuz, Helios

We show that electrically charged solutions within the Eddington-inspired Born-Infeld theory of gravity replace the central singularity by a wormhole supported by the electric field. As a result, the total energy associated with the electric field is finite and similar to that found in the Born-Infeld electromagnetic theory. When a certain charge-to-mass ratio is satisfied, in the lowest part of the mass and charge spectrum the event horizon disappears, yielding stable remnants. We argue that quantum effects in the matter sector can lower the mass of these remnants from the Planck scale down to the TeV scale.

Virus-inspired design principles of nanoparticle-based bioagents.

Directory of Open Access Journals (Sweden)

Hongyan Yuan

Full Text Available The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP-based therapeutics. Through thermodynamic analysis, we elucidate that the mechanisms governing both the endocytic time of a single NP and the cellular uptake can be unified into a general energy-balance framework of NP-membrane adhesion and membrane deformation. Yet the NP-membrane adhesion strength is a globally variable quantity that effectively regulates the NP uptake rate. Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect. Our model predicts that the optimal radius of NPs for maximal uptake rate falls in the range of 25-30 nm, and optimally several tens of ligands should be coated onto NPs. These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine.

Distinct Iron-binding Ligands in the Upper Water Column at Station ALOHA

Science.gov (United States)

Bundy, R.; Boiteau, R.; Repeta, D.

2016-02-01

The distribution and chemical properties of iron-binding organic ligands at station ALOHA were examined using a combination of solid phase extraction (SPE) followed by high pressure liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). HPLC-ICPMS ligand measurements were complemented by competitive ligand exchange adsorptive cathodic stripping voltammetry (CLE-ACSV) analysis using salicylaldoxime as the added ligand. By HPLC-ICPMS, we find enhanced concentrations of distinct naturally-occurring polar iron-binding ligands present at the surface and in the chlorophyll maximum. Lower concentrations were found in the subsurface, where a suite of non-polar ligands was detected. Siderophores were present at the deepest depths sampled at station ALOHA, down to 400m. Incubation studies provided evidence for the production of iron-binding ligands associated with nutrient amended phytoplankton growth in surface waters, and as a result of microbial particle remineralization in the subsurface water column. Ligands classes identified via SPE were then compared to CLE-ACSV ligand measurements, as well as the conditional stability constants measured from model polar and non-polar siderophores, yielding insight to the sources of iron-binding ligands throughout the water column at station ALOHA.

Skin-Inspired Electronics: An Emerging Paradigm.

Science.gov (United States)

Wang, Sihong; Oh, Jin Young; Xu, Jie; Tran, Helen; Bao, Zhenan

2018-05-15

Future electronics will take on more important roles in people's lives. They need to allow more intimate contact with human beings to enable advanced health monitoring, disease detection, medical therapies, and human-machine interfacing. However, current electronics are rigid, nondegradable and cannot self-repair, while the human body is soft, dynamic, stretchable, biodegradable, and self-healing. Therefore, it is critical to develop a new class of electronic materials that incorporate skinlike properties, including stretchability for conformable integration, minimal discomfort and suppressed invasive reactions; self-healing for long-term durability under harsh mechanical conditions; and biodegradability for reducing environmental impact and obviating the need for secondary device removal for medical implants. These demands have fueled the development of a new generation of electronic materials, primarily composed of polymers and polymer composites with both high electrical performance and skinlike properties, and consequently led to a new paradigm of electronics, termed "skin-inspired electronics". This Account covers recent important advances in skin-inspired electronics, from basic material developments to device components and proof-of-concept demonstrations for integrated bioelectronics applications. To date, stretchability has been the most prominent focus in this field. In contrast to strain-engineering approaches that extrinsically impart stretchability into inorganic electronics, intrinsically stretchable materials provide a direct route to achieve higher mechanical robustness, higher device density, and scalable fabrication. The key is the introduction of strain-dissipation mechanisms into the material design, which has been realized through molecular engineering (e.g., soft molecular segments, dynamic bonds) and physical engineering (e.g., nanoconfinement effect, geometric design). The material design concepts have led to the successful demonstrations of

Learning from nature: Nature-inspired algorithms

DEFF Research Database (Denmark)

Albeanu, Grigore; Madsen, Henrik; Popentiu-Vladicescu, Florin

2016-01-01

.), genetic and evolutionary strategies, artificial immune systems etc. Well-known examples of applications include: aircraft wing design, wind turbine design, bionic car, bullet train, optimal decisions related to traffic, appropriate strategies to survive under a well-adapted immune system etc. Based......During last decade, the nature has inspired researchers to develop new algorithms. The largest collection of nature-inspired algorithms is biology-inspired: swarm intelligence (particle swarm optimization, ant colony optimization, cuckoo search, bees' algorithm, bat algorithm, firefly algorithm etc...... on collective social behaviour of organisms, researchers have developed optimization strategies taking into account not only the individuals, but also groups and environment. However, learning from nature, new classes of approaches can be identified, tested and compared against already available algorithms...

Bio-Inspired Interaction Control of Robotic Machines for Motor Therapy

OpenAIRE

Zollo, Loredana; Formica, Domenico; Guglielmelli, Eugenio

2007-01-01

In this chapter basic criteria for the design and implementation of interaction control of robotic machines for motor therapy have been briefly introduced and two bio-inspired compliance control laws developed by the authors to address requirements coming from this specific application field have been presented. The two control laws are named the coactivation-based compliance control in the joint space and the torque-dependent compliance control in the joint space, respectively. They try to o...

Bio-inspired UAV routing, source localization, and acoustic signature classification for persistent surveillance

Science.gov (United States)

Burman, Jerry; Hespanha, Joao; Madhow, Upamanyu; Pham, Tien

2011-06-01

A team consisting of Teledyne Scientific Company, the University of California at Santa Barbara and the Army Research Laboratory* is developing technologies in support of automated data exfiltration from heterogeneous battlefield sensor networks to enhance situational awareness for dismounts and command echelons. Unmanned aerial vehicles (UAV) provide an effective means to autonomously collect data from a sparse network of unattended ground sensors (UGSs) that cannot communicate with each other. UAVs are used to reduce the system reaction time by generating autonomous collection routes that are data-driven. Bio-inspired techniques for search provide a novel strategy to detect, capture and fuse data. A fast and accurate method has been developed to localize an event by fusing data from a sparse number of UGSs. This technique uses a bio-inspired algorithm based on chemotaxis or the motion of bacteria seeking nutrients in their environment. A unique acoustic event classification algorithm was also developed based on using swarm optimization. Additional studies addressed the problem of routing multiple UAVs, optimally placing sensors in the field and locating the source of gunfire at helicopters. A field test was conducted in November of 2009 at Camp Roberts, CA. The field test results showed that a system controlled by bio-inspired software algorithms can autonomously detect and locate the source of an acoustic event with very high accuracy and visually verify the event. In nine independent test runs of a UAV, the system autonomously located the position of an explosion nine times with an average accuracy of 3 meters. The time required to perform source localization using the UAV was on the order of a few minutes based on UAV flight times. In June 2011, additional field tests of the system will be performed and will include multiple acoustic events, optimal sensor placement based on acoustic phenomenology and the use of the International Technology Alliance (ITA

A qualitative exploration of the wilderness experience as a source of spiritual inspiration

Science.gov (United States)

Laura M. Fredrickson; Dorothy H. Anderson

1999-01-01

On-site observations, personal field journals, and in-depth interviews were used to examine qualitative aspects of the wilderness experience as a source of spiritual inspiration. Two groups of women kept personal journal accounts of their daily 'lived-experience' during one of two outdoor recreation trips; five participants went to the Boundary Waters Canoe...

16th International Conference on Hybrid Intelligent Systems and the 8th World Congress on Nature and Biologically Inspired Computing

CERN Document Server

Haqiq, Abdelkrim; Alimi, Adel; Mezzour, Ghita; Rokbani, Nizar; Muda, Azah

2017-01-01

This book presents the latest research in hybrid intelligent systems. It includes 57 carefully selected papers from the 16th International Conference on Hybrid Intelligent Systems (HIS 2016) and the 8th World Congress on Nature and Biologically Inspired Computing (NaBIC 2016), held on November 21–23, 2016 in Marrakech, Morocco. HIS - NaBIC 2016 was jointly organized by the Machine Intelligence Research Labs (MIR Labs), USA; Hassan 1st University, Settat, Morocco and University of Sfax, Tunisia. Hybridization of intelligent systems is a promising research field in modern artificial/computational intelligence and is concerned with the development of the next generation of intelligent systems. The conference’s main aim is to inspire further exploration of the intriguing potential of hybrid intelligent systems and bio-inspired computing. As such, the book is a valuable resource for practicing engineers /scientists and researchers working in the field of computational intelligence and artificial intelligence.

PLASS: Protein-ligand affinity statistical score a knowledge-based force-field model of interaction derived from the PDB

Science.gov (United States)

Ozrin, V. D.; Subbotin, M. V.; Nikitin, S. M.

2004-04-01

We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken from the Protein Data Bank (PDB). Statistical distributions are converted into distance-dependent contributions to the Gibbs free interaction energy for 10 atomic types using the Boltzmann hypothesis, with only one adjustable parameter. For a representative set of 72 protein-ligand structures, PLASS scores correlate well with the experimentally measured dissociation constants: a correlation coefficient R of 0.82 and RMS error of 2.0 kcal/mol. Such high accuracy results from our novel treatment of the volume correction term, which takes into account the inhomogeneous properties of the protein-ligand complexes. PLASS is able to rank reliably the affinity of complexes which have as much diversity as in the PDB.

A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.

Directory of Open Access Journals (Sweden)

Jarosław Poznański

Full Text Available Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.

LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

KAUST Repository

Chen, Peng; Huang, Jianhua Z; Gao, Xin

2014-01-01

Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

Ligand-protected gold clusters: the structure, synthesis and applications

Science.gov (United States)

Pichugina, D. A.; Kuz'menko, N. E.; Shestakov, A. F.

2015-11-01

Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Aun with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au15 and Au25) and on anchorage to a support surface (Au25/SiO2, Au20/C, Au10/FeOx) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR)n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters MxAunLm (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR)x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active sites. The bibliography includes 345 references.

Trends & Challenges in Neuroengineering: Towards ‘Intelligent’ Neuroprostheses through Brain-‘Brain Inspired Systems’ Communication

Directory of Open Access Journals (Sweden)

Stefano Vassanelli

2016-09-01

Full Text Available Future technologies aiming at restoring and enhancing organs function will intimately rely on near-physiological and energy-efficient communication between living and artificial biomimetic systems. Interfacing brain-inspired devices with the real brain is at the forefront of such emerging field, with the term ‘neurobiohybrids’ indicating all those systems where such interaction is established. We argue that achieving a ‘high-level’ communication and functional synergy between natural and artificial neuronal networks in vivo, will allow the development of a heterogeneous world of neurobiohybrids, which will include ‘living robots’ but will also embrace ‘intelligent’ neuroprostheses for augmentation of brain function. The societal and economical impact of intelligent neuroprostheses is likely to be potentially strong, as they will offer novel therapeutic perspectives for a number of diseases, and going beyond classical pharmaceutical schemes. However, they will unavoidably raise fundamental ethical questions on the intermingling between man and machine and, more specifically, on how deeply it should be allowed that brain processing is affected by implanted ‘intelligent’ artificial systems.Following this perspective, we provide the reader with insights on ongoing developments and trends in the field of neurobiohybrids. We address the topic also from a ‘community building’ perspective, showing through a quantitative bibliographic analysis, how scientists working on the engineering of brain-inspired devices and brain-machine interfaces are increasing their interactions. We foresee that such trend preludes to a formidable technological and scientific revolution in brain-machine communication and to the opening of new avenues for restoring or even augmenting brain function for therapeutic purposes.

Practices of Waldorf-Inspired Schools. Research Brief

Science.gov (United States)

Friedlaender, Diane; Beckham, Kyle; Zheng, Xinhua; Darling-Hammond, Linda

2015-01-01

"Growing a Waldorf-Inspired Approach in a Public School District" documents the practices and outcomes of Alice Birney, a Waldorf-Inspired School in Sacramento City Unified School District (SCUSD). This study highlights how such a school addresses students' academic, social, emotional, physical, and creative development. The study also…

Analysis of a Scenario for Chaotic Quantal Slowing Down of Inspiration

Science.gov (United States)

2013-01-01

On exposure to opiates, preparations from rat brain stems have been observed to continue to produce regular expiratory signals, but to fail to produce some inspiratory signals. The numbers of expirations between two successive inspirations form an apparently random sequence. Here, we propose an explanation based on the qualitative theory of dynamical systems. A relatively simple scenario for the dynamics of interaction between the generators of expiratory and inspiratory signals produces pseudo-random behaviour of the type observed. PMID:24040967

Evaluation of several two-step scoring functions based on linear interaction energy, effective ligand size, and empirical pair potentials for prediction of protein-ligand binding geometry and free energy.

Science.gov (United States)

Rahaman, Obaidur; Estrada, Trilce P; Doren, Douglas J; Taufer, Michela; Brooks, Charles L; Armen, Roger S

2011-09-26

The performances of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for "step 2 discrimination" were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only "interacting" ligand atoms as the "effective size" of the ligand and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and 5-fold cross-validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new data set (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ data set where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand

Magnetic Ligand Fishing as a Targeting Tool for HPLC-HRMS-SPE-NMR: α-Glucosidase Inhibitory Ligands and Alkylresorcinol Glycosides from Eugenia catharinae.

Science.gov (United States)

Wubshet, Sileshi G; Brighente, Inês M C; Moaddel, Ruin; Staerk, Dan

2015-11-25

A bioanalytical platform combining magnetic ligand fishing for α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR for structural identification of α-glucosidase inhibitory ligands, both directly from crude plant extracts, is presented. Magnetic beads with N-terminus-coupled α-glucosidase were synthesized and characterized for their inherent catalytic activity. Ligand fishing with the immobilized enzyme was optimized using an artificial test mixture consisting of caffeine, ferulic acid, and luteolin before proof-of-concept with the crude extract of Eugenia catharinae. The combination of ligand fishing and HPLC-HRMS-SPE-NMR identified myricetin 3-O-α-L-rhamnopyranoside, myricetin, quercetin, and kaempferol as α-glucosidase inhibitory ligands in E. catharinae. Furthermore, HPLC-HRMS-SPE-NMR analysis led to identification of six new alkylresorcinol glycosides, i.e., 5-(2-oxopentyl)resorcinol 4-O-β-D-glucopyranoside, 5-propylresorcinol 4-O-β-D-glucopyranoside, 5-pentylresorcinol 4-O-[α-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, 5-pentylresorcinol 4-O-β-D-glucopyranoside, 4-hydroxy-3-O-methyl-5-pentylresorcinol 1-O-β-D-glucopyranoside, and 3-O-methyl-5-pentylresorcinol 1-O-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranoside.

Ammonia formation by metal-ligand cooperative hydrogenolysis of a nitrido ligand

Science.gov (United States)

Askevold, Bjorn; Nieto, Jorge Torres; Tussupbayev, Samat; Diefenbach, Martin; Herdtweck, Eberhardt; Holthausen, Max C.; Schneider, Sven

2011-07-01

Bioinspired hydrogenation of N2 to ammonia at ambient conditions by stepwise nitrogen protonation/reduction with metal complexes in solution has experienced remarkable progress. In contrast, the highly desirable direct hydrogenation with H2 remains difficult. In analogy to the heterogeneously catalysed Haber-Bosch process, such a reaction is conceivable via metal-centred N2 splitting and unprecedented hydrogenolysis of the nitrido ligands to ammonia. We report the synthesis of a ruthenium(IV) nitrido complex. The high nucleophilicity of the nitrido ligand is demonstrated by unusual N-C coupling with π-acidic CO. Furthermore, the terminal nitrido ligand undergoes facile hydrogenolysis with H2 at ambient conditions to produce ammonia in high yield. Kinetic and quantum chemical examinations of this reaction suggest cooperative behaviour of a phosphorus-nitrogen-phosphorus pincer ligand in rate-determining heterolytic hydrogen splitting.

Business Inspiration: Small Business Leadership in Recovery?

Science.gov (United States)

Rae, David; Price, Liz; Bosworth, Gary; Parkinson, Paul

2012-01-01

Business Inspiration was a short, action-centred leadership and innovation development programme designed for owners and managers of smaller firms to address business survival and repositioning needs arising from the UK's economic downturn. The article examines the design and delivery of Business Inspiration and the impact of the programme on…

Reduction of dinitrogen ligands

International Nuclear Information System (INIS)

Richards, R.L.

1983-01-01

Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

Ligands and modifiers in vitreous materials the spectroscopy of condensed systems

CERN Document Server

Margaryan, Alfred

1999-01-01

The study of the effect of ligand and modifier ions on the spectroscopic properties of dn or fn elements in vitreous materials is important for the development of controllable lasers and amplifiers. The spectroscopic characteristics of inorganic compounds of transition elements and their solutions are well understood theoretically in the spectrochemistry of complexes, but developments for vitreous materials in these conditions have not been well documented. This book fills the gap by applying the ligand field theory of solid materials to the vitreous state, and presenting the data obtained fro

On-chip visual perception of motion: a bio-inspired connectionist model on FPGA.

Science.gov (United States)

Torres-Huitzil, César; Girau, Bernard; Castellanos-Sánchez, Claudio

2005-01-01

Visual motion provides useful information to understand the dynamics of a scene to allow intelligent systems interact with their environment. Motion computation is usually restricted by real time requirements that need the design and implementation of specific hardware architectures. In this paper, the design of hardware architecture for a bio-inspired neural model for motion estimation is presented. The motion estimation is based on a strongly localized bio-inspired connectionist model with a particular adaptation of spatio-temporal Gabor-like filtering. The architecture is constituted by three main modules that perform spatial, temporal, and excitatory-inhibitory connectionist processing. The biomimetic architecture is modeled, simulated and validated in VHDL. The synthesis results on a Field Programmable Gate Array (FPGA) device show the potential achievement of real-time performance at an affordable silicon area.

Nature as inspiration for leisure education

OpenAIRE

ŠPIRHANZLOVÁ, Andrea

2017-01-01

The thesis deals with the organization of leisure activities where the main tool and inspiration is nature. The theoretical part defines basic concepts of pedagogy of free time and points to the possibility of using nature as an inspiration not only for creating content components of leisure activities, but also as the environment in which the pedagogical - educational process of activities takes place. The practical part contains specific pedagogical - educational activity whose essence is b...

KLIFS : a knowledge-based structural database to navigate kinase-ligand interaction space

NARCIS (Netherlands)

van Linden, O.P.J.; Kooistra, A.J.; Leurs, R.; de Esch, I.J.P.; de Graaf, C.

2013-01-01

Protein kinases regulate the majority of signal transduction pathways in cells and have become important targets for the development of designer drugs. We present a systematic analysis of kinase-ligand interactions in all regions of the catalytic cleft of all 1252 human kinase-ligand cocrystal

Multi-Locomotion Robotic Systems New Concepts of Bio-inspired Robotics

CERN Document Server

Fukuda, Toshio; Sekiyama, Kosuke; Aoyama, Tadayoshi

2012-01-01

Nowadays, multiple attention have been paid on a robot working in the human living environment, such as in the field of medical, welfare, entertainment and so on. Various types of researches are being conducted actively in a variety of fields such as artificial intelligence, cognitive engineering, sensor- technology, interfaces and motion control. In the future, it is expected to realize super high functional human-like robot by integrating technologies in various fields including these types of researches. The book represents new developments and advances in the field of bio-inspired robotics research introducing the state of the art, the idea of multi-locomotion robotic system to implement the diversity of animal motion. It covers theoretical and computational aspects of Passive Dynamic Autonomous Control (PDAC), robot motion control, multi legged walking and climbing as well as brachiation focusing concrete robot systems, components and applications. In addition, gorilla type robot systems are described as...

A bio-inspired electrocommunication system for small underwater robots.

Science.gov (United States)

Wang, Wei; Liu, Jindong; Xie, Guangming; Wen, Li; Zhang, Jianwei

2017-03-29

Weakly electric fishes (Gymnotid and Mormyrid) use an electric field to communicate efficiently (termed electrocommunication) in the turbid waters of confined spaces where other communication modalities fail. Inspired by this biological phenomenon, we design an artificial electrocommunication system for small underwater robots and explore the capabilities of such an underwater robotic communication system. An analytical model for electrocommunication is derived to predict the effect of the key parameters such as electrode distance and emitter current of the system on the communication performance. According to this model, a low-dissipation, and small-sized electrocommunication system is proposed and integrated into a small robotic fish. We characterize the communication performance of the robot in still water, flowing water, water with obstacles and natural water conditions. The results show that underwater robots are able to communicate electrically at a speed of around 1 k baud within about 3 m with a low power consumption (less than 1 W). In addition, we demonstrate that two leader-follower robots successfully achieve motion synchronization through electrocommunication in the three-dimensional underwater space, indicating that this bio-inspired electrocommunication system is a promising setup for the interaction of small underwater robots.

Ligand modeling and design

Energy Technology Data Exchange (ETDEWEB)

Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

1997-10-01

The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

Inspiration and the Texts of the Bible

Directory of Open Access Journals (Sweden)

Dirk Buchner

1997-12-01

Full Text Available This article seeks to explore what the inspired text of the Old Testament was as it existed for the New Testament authors, particularly for the author of the book of Hebrews. A quick look at the facts makes. it clear that there was, at the time, more than one 'inspired' text, among these were the Septuagint and the Masoretic Text 'to name but two'. The latter eventually gained ascendancy which is why it forms the basis of our translated Old Testament today. Yet we have to ask: what do we make of that other text that was the inspired Bible to the early Church, especially to the writer of the book of Hebrews, who ignored the Masoretic text? This article will take a brief look at some suggestions for a doctrine of inspiration that keeps up with the facts of Scripture. Allied to this, the article is something of a bibliographical study of recent developments in textual research following the discovery of the Dead Sea scrolls.

NASA Missions Inspire Online Video Games

Science.gov (United States)

2012-01-01

Fast forward to 2035. Imagine being part of a community of astronauts living and working on the Moon. Suddenly, in the middle of just another day in space, a meteorite crashes into the surface of the Moon, threatening life as you know it. The support equipment that provides oxygen for the entire community has been compromised. What would you do? While this situation is one that most people will never encounter, NASA hopes to place students in such situations - virtually - to inspire, engage, and educate about NASA technologies, job opportunities, and the future of space exploration. Specifically, NASA s Learning Technologies program, part of the Agency s Office of Education, aims to inspire and motivate students to pursue careers in the science, technology, engineering, and math (STEM) disciplines through interactive technologies. The ultimate goal of these educational programs is to support the growth of a pool of qualified scientific and technical candidates for future careers at places like NASA. STEM education has been an area of concern in the United States; according to the results of the 2009 Program for International Student Assessment, 23 countries had higher average scores in mathematics literacy than the United States. On the science literacy scale, 18 countries had higher average scores. "This is part of a much bigger picture of trying to grow skilled graduates for places like NASA that will want that technical expertise," says Daniel Laughlin, the Learning Technologies project manager at Goddard Space Flight Center. "NASA is trying to increase the number of students going into those fields, and so are other government agencies."

Ligand identification using electron-density map correlations

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2007-01-01

An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

Multiple ligand-binding modes in bacterial R67 dihydrofolate reductase

Science.gov (United States)

Alonso, Hernán; Gillies, Malcolm B.; Cummins, Peter L.; Bliznyuk, Andrey A.; Gready, Jill E.

2005-03-01

R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central active-site pore. Two reactants (dihydrofolate, DHF), two cofactors (NADPH) or one of each (R67•DHF•NADPH) can be found simultaneously within the active site, the last one being the reactive ternary complex. As the positioning of the ligands has proven elusive to empirical determination, we addressed the problem from a theoretical perspective. Several potential structures of the ternary complex were generated using the docking programs AutoDock and FlexX. The variability among the final poses, many of which conformed to experimental data, prompted us to perform a comparative scoring analysis and molecular dynamics simulations to assess the stability of the complexes. Analysis of ligand-ligand and ligand-protein interactions along the 4 ns trajectories of eight different structures allowed us to identify important inter-ligand contacts and key protein residues. Our results, combined with published empirical data, clearly suggest that multipe binding modes of the ligands are possible within R67 DHFR. While the pterin ring of DHF and the nicotinamide ring of NADPH assume a stacked endo-conformation at the centre of the pore, probably assisted by V66, Q67 and I68, the tails of the molecules extend towards opposite ends of the cavity, adopting multiple configurations in a solvent rich-environment where hydrogen-bond interactions with K32 and Y69 may play important roles.

Schiff base ligand

Indian Academy of Sciences (India)

Unknown

Low-temperature stoichiometric Schiff base reaction in air in 3 : 1 mole ratio between benz- aldehyde and triethylenetetramine (trien) in methanol yields a novel tetraaza µ-bis(bidentate) acyclic ligand L. It was .... electrochemical work was performed as reported in ..... change in ligand shape through change in oxidation.

Capping Ligand Vortices as "Atomic Orbitals" in Nanocrystal Self-Assembly.

Science.gov (United States)

Waltmann, Curt; Horst, Nathan; Travesset, Alex

2017-11-28

We present a detailed analysis of the interaction between two nanocrystals capped with ligands consisting of hydrocarbon chains by united atom molecular dynamics simulations. We show that the bonding of two nanocrystals is characterized by ligand textures in the form of vortices. These results are generalized to nanocrystals of different types (differing core and ligand sizes) where the structure of the vortices depends on the softness asymmetry. We provide rigorous calculations for the binding free energy, show that these energies are independent of the chemical composition of the cores, and derive analytical formulas for the equilibrium separation. We discuss the implications of our results for the self-assembly of single-component and binary nanoparticle superlattices. Overall, our results show that the structure of the ligands completely determines the bonding of nanocrystals, fully supporting the predictions of the recently proposed Orbifold topological model.

Nature-Inspired Design : Strategies for Sustainable Product Development

NARCIS (Netherlands)

De Pauw, I.C.

2015-01-01

Product designers can apply different strategies, methods, and tools for sustainable product development. Nature-Inspired Design Strategies (NIDS) offer designers a distinct class of strategies that use ‘nature’ as a guiding source of knowledge and inspiration for addressing sustainability.

The scientific study of inspiration in the creative process: Challenges and opportunities

Directory of Open Access Journals (Sweden)

Victoria C. Oleynick

2014-06-01

Full Text Available Inspiration is a motivational state that compels individuals to bring ideas into fruition. Creators have long argued that inspiration is important to the creative process, but until recently, scientists have not investigated this claim. In this article, we review challenges to the study of creative inspiration, as well as solutions to these challenges afforded by theoretical and empirical work on inspiration over the past decade. First, we discuss the problem of definitional ambiguity, which has been addressed through an integrative process of construct conceptualization. Second, we discuss the challenge of how to operationalize inspiration. This challenge has been overcome by the development and validation of the Inspiration Scale, which may be used to assess trait or state inspiration. Third, we address ambiguity regarding how inspiration differs from related concepts (creativity, insight, positive affect by discussing discriminant validity. Next, we discuss the preconception that inspiration is less important than perspiration (effort, and we review empirical evidence that inspiration and effort both play important—but different—roles in the creative process. Finally, with many challenges overcome, we argue that the foundation is now set for a new generation of research focused on neural underpinnings. We discuss potential challenges to and opportunities for the neuroscientific study of inspiration. A better understanding of the biological basis of inspiration will illuminate the process through which creative ideas fire the soul, such that individuals are compelled to transform ideas into products and solutions that may benefit society.

Residue preference mapping of ligand fragments in the Protein Data Bank.

Science.gov (United States)

Wang, Lirong; Xie, Zhaojun; Wipf, Peter; Xie, Xiang-Qun

2011-04-25

The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables unprecedented possibilities for new insights. Herein, we applied molecule-fragmentation algorithms to split the ligands extracted from PDB crystal structures into small fragments. Subsequently, we have developed a ligand fragment and residue preference mapping (LigFrag-RPM) algorithm to map the profiles of the interactions between these fragments and the 20 proteinogenic amino acid residues. A total of 4032 fragments were generated from 71 798 PDB ligands by a ring cleavage (RC) algorithm. Among these ligand fragments, 315 unique fragments were characterized with the corresponding fragment-residue interaction profiles by counting residues close to these fragments. The interaction profiles revealed that these fragments have specific preferences for certain types of residues. The applications of these interaction profiles were also explored and evaluated in case studies, showing great potential for the study of protein-ligand interactions and drug design. Our studies demonstrated that the fragment-residue interaction profiles generated from the PDB ligand fragments can be used to detect whether these fragments are in their favorable or unfavorable environments. The algorithm for a ligand fragment and residue preference mapping (LigFrag-RPM) developed here also has the potential to guide lead chemistry modifications as well as binding residues predictions.

3D-QSAR comparative molecular field analysis on opioid receptor antagonists: pooling data from different studies.

Science.gov (United States)

Peng, Youyi; Keenan, Susan M; Zhang, Qiang; Kholodovych, Vladyslav; Welsh, William J

2005-03-10

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) on a series of opioid receptor antagonists. To obtain statistically significant and robust CoMFA models, a sizable data set of naltrindole and naltrexone analogues was assembled by pooling biological and structural data from independent studies. A process of "leave one data set out", similar to the traditional "leave one out" cross-validation procedure employed in partial least squares (PLS) analysis, was utilized to study the feasibility of pooling data in the present case. These studies indicate that our approach yields statistically significant and highly predictive CoMFA models from the pooled data set of delta, mu, and kappa opioid receptor antagonists. All models showed excellent internal predictability and self-consistency: q(2) = 0.69/r(2) = 0.91 (delta), q(2) = 0.67/r(2) = 0.92 (mu), and q(2) = 0.60/r(2) = 0.96 (kappa). The CoMFA models were further validated using two separate test sets: one test set was selected randomly from the pooled data set, while the other test set was retrieved from other published sources. The overall excellent agreement between CoMFA-predicted and experimental binding affinities for a structurally diverse array of ligands across all three opioid receptor subtypes gives testimony to the superb predictive power of these models. CoMFA field analysis demonstrated that the variations in binding affinity of opioid antagonists are dominated by steric rather than electrostatic interactions with the three opioid receptor binding sites. The CoMFA steric-electrostatic contour maps corresponding to the delta, mu, and kappa opioid receptor subtypes reflected the characteristic similarities and differences in the familiar "message-address" concept of opioid receptor ligands. Structural modifications to increase selectivity for the delta over mu and kappa opioid receptors have been predicted on the

Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

Directory of Open Access Journals (Sweden)

Forgacs Agnes L

2009-04-01

Full Text Available Abstract Background Tamoxifen (TAM is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level in vivo.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge. Results A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns. Conclusion Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.

ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites.

Science.gov (United States)

Konc, Janez; Janežič, Dušanka

2014-07-01

The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Late inspiral and merger of binary black holes in scalar–tensor theories of gravity

International Nuclear Information System (INIS)

Healy, James; Bode, Tanja; Laguna, Pablo; Shoemaker, Deirdre M; Haas, Roland; Pazos, Enrique; Yunes, Nicolás

2012-01-01

Gravitational wave observations will probe nonlinear gravitational interactions and thus enable strong tests of Einstein’s theory of general relativity. We present a numerical relativity study of the late inspiral and merger of binary black holes in scalar–tensor theories of gravity. We consider binaries inside a scalar field bubble, including in some cases a potential. We demonstrate how an evolving scalar field is able to trigger detectable differences between gravitational waves in scalar–tensor gravity and the corresponding waves in general relativity. (fast track communication)

Role of Cultural Inspiration with Different Types in Cultural Product Design Activities

Science.gov (United States)

Luo, Shi-Jian; Dong, Ye-Nan

2017-01-01

Inspiration plays an important role in the design activities and design education. This paper describes "ancient cultural artefacts" as "cultural inspiration," consisting of two types called "cultural-pictorial inspiration" (CPI) and "cultural-textual inspiration" (CTI). This study aims to test the important…

Interaction of calreticulin with CD40 ligand, TRAIL and Fas ligand

DEFF Research Database (Denmark)

Duus, K; Pagh, R T; Holmskov, U

2007-01-01

is utilized by many other functionally diverse molecules and in this work the interaction of calreticulin with C1q and structurally similar molecules was investigated. In addition to C1q and MBL, CD40 ligand (CD40L), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) were...... found to bind calreticulin strongly. A low level or no binding was observed for adiponectin, tumour necrosis factor-alpha (TNF-alpha), CD30L, surfactant protein-A and -D and collagen VIII. The interaction with calreticulin required a conformational change in CD40L, TRAIL and FasL and showed the same...

INSPIRE: Interactive NASA Space Physics Ionosphere Radio Experiment

Science.gov (United States)

Franzen, K. A.; Garcia, L. N.; Webb, P. A.; Green, J. L.

2007-12-01

The INSPIRE Project is a non-profit scientific and educational corporation whose objective is to bring the excitement of observing very low frequency (VLF) natural radio waves to high school students. Underlying this objective is the conviction that science and technology are the underpinnings of our modern society, and that only with an understanding of these disciplines can people make correct decisions in their lives. Since 1989, the INSPIRE Project has provided specially designed radio receiver kits to over 2,500 students and other groups to make observations of signals in the VLF frequency range. These kits provide an innovative and unique opportunity for students to actively gather data that can be used in a basic research project. Natural VLF emissions that can be studied with the INSPIRE receiver kits include sferics, tweeks, whistlers, and chorus, which originate from phenomena such as lightning. These emissions can either come from the local atmospheric environment within a few tens of kilometers of the receiver or from outer space thousands of kilometers from the Earth. VLF emissions are at such low frequencies that they can be received, amplified and turned into sound that we can hear, with each emission producing in a distinctive sound. In 2006 INSPIRE was re-branded and its mission has expanded to developing new partnerships with multiple science projects. Links to magnetospheric physics, astronomy, and meteorology are being identified. This presentation will introduce the INSPIRE project, display the INSPIRE receiver kits, show examples of the types of VLF emissions that can be collected and provide information on scholarship programs being offered.

7th World Congress on Nature and Biologically Inspired Computing

CERN Document Server

Engelbrecht, Andries; Abraham, Ajith; Plessis, Mathys; Snášel, Václav; Muda, Azah

2016-01-01

World Congress on Nature and Biologically Inspired Computing (NaBIC) is organized to discuss the state-of-the-art as well as to address various issues with respect to Nurturing Intelligent Computing Towards Advancement of Machine Intelligence. This Volume contains the papers presented in the Seventh World Congress (NaBIC’15) held in Pietermaritzburg, South Africa during December 01-03, 2015. The 39 papers presented in this Volume were carefully reviewed and selected. The Volume would be a valuable reference to researchers, students and practitioners in the computational intelligence field.

Ant- and Ant-Colony-Inspired ALife Visual Art.

Science.gov (United States)

Greenfield, Gary; Machado, Penousal

2015-01-01

Ant- and ant-colony-inspired ALife art is characterized by the artistic exploration of the emerging collective behavior of computational agents, developed using ants as a metaphor. We present a chronology that documents the emergence and history of such visual art, contextualize ant- and ant-colony-inspired art within generative art practices, and consider how it relates to other ALife art. We survey many of the algorithms that artists have used in this genre, address some of their aims, and explore the relationships between ant- and ant-colony-inspired art and research on ant and ant colony behavior.

A recursive field-normalized bibliometric performance indicator: an application to the field of library and information science.

Science.gov (United States)

Waltman, Ludo; Yan, Erjia; van Eck, Nees Jan

2011-10-01

Two commonly used ideas in the development of citation-based research performance indicators are the idea of normalizing citation counts based on a field classification scheme and the idea of recursive citation weighing (like in PageRank-inspired indicators). We combine these two ideas in a single indicator, referred to as the recursive mean normalized citation score indicator, and we study the validity of this indicator. Our empirical analysis shows that the proposed indicator is highly sensitive to the field classification scheme that is used. The indicator also has a strong tendency to reinforce biases caused by the classification scheme. Based on these observations, we advise against the use of indicators in which the idea of normalization based on a field classification scheme and the idea of recursive citation weighing are combined.

Nature as Inspiration

Science.gov (United States)

Tank, Kristina; Moore, Tamara; Strnat, Meg

2015-01-01

This article describes the final lesson within a seven-day STEM and literacy unit that is part of the Picture STEM curriculum (pictureSTEM. org) and uses engineering to integrate science and mathematics learning in a meaningful way (Tank and Moore 2013). For this engineering challenge, students used nature as a source of inspiration for designs to…

Ndebele Inspired Houses

Science.gov (United States)

Rice, Nicole

2012-01-01

The house paintings of the South African Ndebele people are more than just an attempt to improve the aesthetics of a community; they are a source of identity and significance for Ndebele women. In this article, the author describes an art project wherein students use the tradition of Ndebele house painting as inspiration for creating their own…

Media Pembelajaran Interaktif Lectora Inspire sebagai Inovasi Pembelajaran

Directory of Open Access Journals (Sweden)

Norma Dewi Shalikhah

2017-06-01

Full Text Available Abstract The utilization of information and communication technology in education sector is a tremendous output. Support of ICT is hoped to become an innovation in learning with many involving information technology components inside. Therefore, in globalization era, education sector can not pass from its extent, with involves the inherent technology can produce a system of education. This paper discusses the interactive learning media that involve education technology using lectora inspire application. Lectora inspire is designed specifically for the beginner with purpose user friendly to use to make learning media, and can make the material test or evaluation. The development of interactive learning media with lectora inspire is conducted with how to provide training to the teachers in the elementary school. The methods are done with phases, includes gathering information, planning tools, implementing, presenting and reflecting. The object of this training is MIM Jagalan and MIM Jumoyo Greeting sub Magelang regency. Keywords: Media Interactive Learning, Lectora Inspire, Learning Innovation

Bitopic Ligands and Metastable Binding Sites

DEFF Research Database (Denmark)

Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

2017-01-01

of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

Inference on inspiral signals using LISA MLDC data

International Nuclear Information System (INIS)

Roever, Christian; Stroeer, Alexander; Bloomer, Ed; Christensen, Nelson; Clark, James; Hendry, Martin; Messenger, Chris; Meyer, Renate; Pitkin, Matt; Toher, Jennifer; Umstaetter, Richard; Vecchio, Alberto; Veitch, John; Woan, Graham

2007-01-01

In this paper, we describe a Bayesian inference framework for the analysis of data obtained by LISA. We set up a model for binary inspiral signals as defined for the Mock LISA Data Challenge 1.2 (MLDC), and implemented a Markov chain Monte Carlo (MCMC) algorithm to facilitate exploration and integration of the posterior distribution over the nine-dimensional parameter space. Here, we present intermediate results showing how, using this method, information about the nine parameters can be extracted from the data

Biomimicry as an approach for bio-inspired structure with the aid of compu

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Moheb Sabry Aziz

2016-03-01

Full Text Available Biomimicry is the study of emulating and mimicking nature, where it has been used by designers to help in solving human problems. From centuries ago designers and architects looked at nature as a huge source of inspiration. Biomimicry argues that nature is the best, most influencing and the guaranteed source of innovation for the designers as a result of nature’s 3.85 billion years of evolution, as it holds a gigantic experience of solving problems of the environment and its inhabitants. The biomimicry emerging field deals with new technologies honed from bio-inspired engineering at the micro and macro scale levels. Architects have been searching for answers from nature to their complex questions about different kinds of structures, and they have mimicked a lot of forms from nature to create better and more efficient structures for different architectural purposes. Without computers these complex ways and forms of structures couldn’t been mimicked and thus using computers had risen the way of mimicking and taking inspiration from nature because it is considered a very sophisticated and accurate tool for simulation and computing, as a result designers can imitate different nature’s models in spite of its complexity.

Bio-inspired synthesis and characterization of superparamagnetic particles; Sintese e caracterizacao bioinspirada de particulas superparamagneticas

Energy Technology Data Exchange (ETDEWEB)

Castro, Vinicius F., E-mail: vfc_mg@yahoo.com.br [Universidade Federal de Itajuba (UNIFEI), MG (Brazil); Queiroz, Alvaro A.A. [Universidade Federal de Itajuba (UNIFEI), MG (Brazil). Centro de Estudos e Inovacao em Materiais Biofuncionais Avancados

2012-08-15

This paper discusses the bio-inspired synthesis of type YFeAl ferrites encapsulated into polyglycerol dendrimers (PGLD) generation 3. The structure and morphological properties of the system YFeAl/PGLD was characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The magnetic properties were studied through the techniques of Moessbauer spectroscopy and magnetization. The cytotoxicity of the nanoparticles encapsulated in dendrimers PGLD G3 at the cell membrane was studied against mammalian cell line CHO.K1 measuring the amount of lactate dehydrogenase (LDH) released by the cell damage. Microscopy TEM and XRD analysis indicate that spherical nanoparticles were obtained highly crystalline and monodisperse with size 20 nmanalysis and study of magnetization of the nanoparticles compared to a magnetic field indicated superparamagnetic behavior of the system YFeAl/PGLD. The cytotoxicity results indicated that YFeAl / PGLD nano system is suitable for use in nano medicine. (author)

Gaze inspired subtitle position evaluation for MOOCs videos

Science.gov (United States)

Chen, Hongli; Yan, Mengzhen; Liu, Sijiang; Jiang, Bo

2017-06-01

Online educational resources, such as MOOCs, is becoming increasingly popular, especially in higher education field. One most important media type for MOOCs is course video. Besides traditional bottom-position subtitle accompany to the videos, in recent years, researchers try to develop more advanced algorithms to generate speaker-following style subtitles. However, the effectiveness of such subtitle is still unclear. In this paper, we investigate the relationship between subtitle position and the learning effect after watching the video on tablet devices. Inspired with image based human eye tracking technique, this work combines the objective gaze estimation statistics with subjective user study to achieve a convincing conclusion - speaker-following subtitles are more suitable for online educational videos.

Actions, Observations, and Decision-Making: Biologically Inspired Strategies for Autonomous Aerial Vehicles

Science.gov (United States)

Pisanich, Greg; Ippolito, Corey; Plice, Laura; Young, Larry A.; Lau, Benton

2003-01-01

This paper details the development and demonstration of an autonomous aerial vehicle embodying search and find mission planning and execution srrategies inspired by foraging behaviors found in biology. It begins by describing key characteristics required by an aeria! explorer to support science and planetary exploration goals, and illustrates these through a hypothetical mission profile. It next outlines a conceptual bio- inspired search and find autonomy architecture that implements observations, decisions, and actions through an "ecology" of producer, consumer, and decomposer agents. Moving from concepts to development activities, it then presents the results of mission representative UAV aerial surveys at a Mars analog site. It next describes hardware and software enhancements made to a commercial small fixed-wing UAV system, which inc!nde a ncw dpvelopnent architecture that also provides hardware in the loop simulation capability. After presenting the results of simulated and actual flights of bioinspired flight algorithms, it concludes with a discussion of future development to include an expansion of system capabilities and field science support.

Ligand-protected gold clusters: the structure, synthesis and applications

International Nuclear Information System (INIS)

Pichugina, D A; Kuz'menko, N E; Shestakov, A F

2015-01-01

Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Au n with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au 15 and Au 25 ) and on anchorage to a support surface (Au 25 /SiO 2 , Au 20 /C, Au 10 /FeO x ) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR) n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters M x Au n L m (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR) x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active

Biologically inspired technologies in NASA's morphing project

Science.gov (United States)

McGowan, Anna-Maria R.; Cox, David E.; Lazos, Barry S.; Waszak, Martin R.; Raney, David L.; Siochi, Emilie J.; Pao, S. Paul

2003-07-01

For centuries, biology has provided fertile ground for hypothesis, discovery, and inspiration. Time-tested methods used in nature are being used as a basis for several research studies conducted at the NASA Langley Research Center as a part of Morphing Project, which develops and assesses breakthrough vehicle technologies. These studies range from low drag airfoil design guided by marine and avian morphologies to soaring techniques inspired by birds and the study of small flexible wing vehicles. Biology often suggests unconventional yet effective approaches such as non-planar wings, dynamic soaring, exploiting aeroelastic effects, collaborative control, flapping, and fibrous active materials. These approaches and other novel technologies for future flight vehicles are being studied in NASA's Morphing Project. This paper will discuss recent findings in the aeronautics-based, biologically-inspired research in the project.

Design and Analysis of a Bio-Inspired Wire-Driven Multi-Section Flexible Robot

Directory of Open Access Journals (Sweden)

Zheng Li

2013-04-01

Full Text Available This paper presents a bio-inspired wire-driven multi-section flexible robot. It is inspired by the snake skeleton and octopus arm muscle arrangements. The robot consists of three sections and each section is made up of several identical vertebras, which are articulated by both spherical joints and a flexible backbone. Each section is driven by two groups of wires, controlling the bending motion in X and Y directions. This design integrates the serpentine robots' structure and the continuum robots' actuation. As a result, it is more compact than traditional serpentine robots and has a higher positioning accuracy than typical continuum soft robots, such as OctArm V. A Kinematics model and a workspace model of the robot are developed based on the piece wise constant curvature assumption. To evaluate the design, a prototype is built and experiments are carried out. The average distal end positioning error is less than 4%. Characteristics of the wire-driven robot are also discussed, including the leverage effect and the manipulability under constraint. These features makes the proposed robot well suited to confined spaces, especially for working in minimally invasive surgery, nuclear reactor pipelines, disaster debris, etc.

INFLUENCE OF NATURAL AND SYNTHETIC ORGANIC LIGANDS ON THE STABILITY AND MOBILITY OF REDUCED TC(IV)

Energy Technology Data Exchange (ETDEWEB)

Nathalie A. Wall; Baohua Gu

2012-12-20

The primary objectives were (1) to quantify the interactions of organic ligands with Tc(IV) through the generation of thermodynamic (complexation) and kinetic parameters needed to assess and predict the mobility of reduced Tc(IV) at DOE contaminated sites; and (2) to determine the impact of organic ligands on the mobility and fate of reduced Tc(IV) under field geochemical conditions.

Inspiration in the Act of Reading

DEFF Research Database (Denmark)

Zeller, Kinga

2016-01-01

In German-language theology, Professor Ulrich H. J. Körtner’s theory of inspiration, as it relates to the Bible reader’s perspective, is well known. His attempt to gain fruitful insights from contemporary literary hermeneutics while linking them to theological concerns makes his approach a valued...... yet not uncontroversial example of a reception-aesthetics twist on the Lutheran sola Scriptura. This article presents Körtner’s hermeneutical considerations with special regard to inspiration related to the Bible reader’s perspective and shows how this approach may be related to some aspects...

Biologically inspired EM image alignment and neural reconstruction.

Science.gov (United States)

Knowles-Barley, Seymour; Butcher, Nancy J; Meinertzhagen, Ian A; Armstrong, J Douglas

2011-08-15

Three-dimensional reconstruction of consecutive serial-section transmission electron microscopy (ssTEM) images of neural tissue currently requires many hours of manual tracing and annotation. Several computational techniques have already been applied to ssTEM images to facilitate 3D reconstruction and ease this burden. Here, we present an alternative computational approach for ssTEM image analysis. We have used biologically inspired receptive fields as a basis for a ridge detection algorithm to identify cell membranes, synaptic contacts and mitochondria. Detected line segments are used to improve alignment between consecutive images and we have joined small segments of membrane into cell surfaces using a dynamic programming algorithm similar to the Needleman-Wunsch and Smith-Waterman DNA sequence alignment procedures. A shortest path-based approach has been used to close edges and achieve image segmentation. Partial reconstructions were automatically generated and used as a basis for semi-automatic reconstruction of neural tissue. The accuracy of partial reconstructions was evaluated and 96% of membrane could be identified at the cost of 13% false positive detections. An open-source reference implementation is available in the Supplementary information. seymour.kb@ed.ac.uk; douglas.armstrong@ed.ac.uk Supplementary data are available at Bioinformatics online.

Supporting STEM Teachers to Inspire through Everyday Innovation

Science.gov (United States)

Bienkowski, Marie; Shechtman, Nicole; Remold, Julie; Knudsen, Jennifer

2014-01-01

Science teachers inspire in part by their constant adaptation to the learning needs of their students and to evolving content, curriculum, technology, and student populations. Innovation--bringing novel things to a situation to confer a benefit--is an integral part of teaching overall, and in especially inspired science teaching. While innovation…

Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb.

Science.gov (United States)

Wilkinson, Malcolm H; Sia, Kah-Ling; Skuza, Elizabeth M; Brodecky, Vojta; Berger, Philip J

2005-02-01

We examined the effect of hypoxia and hypercapnia administered during deliberately induced periodic breathing (PB) in seven lambs following posthyperventilation apnea. Based on our theoretical analysis, the sensitivity or loop gain (LG) of the respiratory control system of the lamb is directly proportional to the difference between alveolar PO2 and inspired PO2. This analysis indicates that during PB, when by necessity LG is >1, replacement of the inspired gas with one of reduced PO2 lowers LG; if we made inspired PO2 approximate alveolar PO2, we predict that LG would be approximately zero and breathing would promptly stabilize. In six lambs, we switched the inspired gas from an inspiratory oxygen fraction of 0.4 to one of 0.12 during an epoch of PB; PB was immediately suppressed, supporting the view that the peripheral chemoreceptors play a pivotal role in the genesis and control of unstable breathing in the lamb. In the six lambs in which we administered hypercapnic gas during PB, breathing instability was also suppressed, but only after a considerable time lag, indicating the CO2 effect is likely to have been mediated through the central chemoreceptors. When we simulated both interventions in a published model of the adult respiratory controller, PB was immediately suppressed by CO2 inhalation and exacerbated by inhalation of hypoxic gas. These fundamentally different responses in lambs and adult humans demonstrate that PB has differing underlying mechanisms in the two species.

Modified Eddington-inspired-Born-Infeld Gravity with a Trace Term

Energy Technology Data Exchange (ETDEWEB)

Chen, Che-Yu [National Taiwan University, Department of Physics, Taipei (China); LeCosPA, National Taiwan University, Taipei (China); National Taiwan University, Graduate Institute of Astrophysics, Taipei (China); Bouhmadi-Lopez, Mariam [Universidade da Beira Interior, Departamento de Fisica, Covilha (Portugal); Centro de Matematica e Aplicacoes da Universidade da Beira Interior (CMA-UBI), Covilha (Portugal); University of the Basque Country UPV/EHU, Department of Theoretical Physics, P.O. Box 644, Bilbao (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao (Spain); Chen, Pisin [National Taiwan University, Department of Physics, Taipei (China); LeCosPA, National Taiwan University, Taipei (China); National Taiwan University, Graduate Institute of Astrophysics, Taipei (China); Stanford University, SLAC National Accelerator Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Stanford, CA (United States)

2016-01-15

In this paper, a modified Eddington-inspired-Born-Infeld (EiBI) theory with a pure trace term g{sub μν}R being added to the determinantal action is analysed from a cosmological point of view. It corresponds to the most general action constructed from a rank two tensor that contains up to first order terms in curvature. This term can equally be seen as a conformal factor multiplying the metric g{sub μν}. This very interesting type of amendment has not been considered within the Palatini formalism despite the large amount of works on the Born-Infeld-inspired theory of gravity. This model can provide smooth bouncing solutions which were not allowed in the EiBI model for the same EiBI coupling. Most interestingly, for a radiation filled universe there are some regions of the parameter space that can naturally lead to a de Sitter inflationary stage without the need of any exotic matter field. Finally, in this model we discover a new type of cosmic ''quasi-sudden'' singularity, where the cosmic time derivative of the Hubble rate becomes very large but finite at a finite cosmic time. (orig.)

Analysis of protein stability and ligand interactions by thermal shift assay.

Science.gov (United States)

Huynh, Kathy; Partch, Carrie L

2015-02-02

Purification of recombinant proteins for biochemical assays and structural studies is time-consuming and presents inherent difficulties that depend on the optimization of protein stability. The use of dyes to monitor thermal denaturation of proteins with sensitive fluorescence detection enables rapid and inexpensive determination of protein stability using real-time PCR instruments. By screening a wide range of solution conditions and additives in a 96-well format, the thermal shift assay easily identifies conditions that significantly enhance the stability of recombinant proteins. The same approach can be used as an initial low-cost screen to discover new protein-ligand interactions by capitalizing on increases in protein stability that typically occur upon ligand binding. This unit presents a methodological workflow for small-scale, high-throughput thermal denaturation of recombinant proteins in the presence of SYPRO Orange dye. Copyright © 2015 John Wiley & Sons, Inc.

Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human basophils.

Science.gov (United States)

Hirano, Toru; Arimitsu, Junsuke; Higa, Shinji; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Kawase, Ichiro; Tanaka, Toshio

2006-01-01

We have previously shown that flavonoids such as luteolin, apigenin and fisetin inhibit interleukin 4 and interleukin 13 production. In this study, we investigated whether luteolin can suppress CD40 ligand expression by basophils. A human basophilic cell line, KU812, was stimulated with A23187 and phorbol myristate acetate (PMA) with or without various concentrations of luteolin or other flavonoids for 12 h, and CD40 ligand expression was analyzed by FACS. The effect of luteolin on CD40 ligand mRNA expression was studied by semiquantitative reverse transcription PCR analysis. In addition, CD40 ligand expression was also measured in purified basophils that had been stimulated for 12 h with A23187 plus PMA with or without various concentrations of luteolin. CD40 ligand expression by KU812 cells was enhanced noticeably in response to A23187 and even more strikingly augmented by A23187 plus PMA. The expression was significantly suppressed by 10 or 30 microM of luteolin, whereas myricetin failed to inhibit. Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM showed a significant inhibitory effect on CD40 ligand expression. The incubation of purified basophils with A23187 plus PMA significantly enhanced CD40 ligand expression, and the presence of luteolin again had an inhibitory effect. Luteolin inhibits CD40 ligand expression by activated basophils.

Advances in bio-inspired computing for combinatorial optimization problems

CERN Document Server

Pintea, Camelia-Mihaela

2013-01-01

Advances in Bio-inspired Combinatorial Optimization Problems' illustrates several recent bio-inspired efficient algorithms for solving NP-hard problems.Theoretical bio-inspired concepts and models, in particular for agents, ants and virtual robots are described. Large-scale optimization problems, for example: the Generalized Traveling Salesman Problem and the Railway Traveling Salesman Problem, are solved and their results are discussed.Some of the main concepts and models described in this book are: inner rule to guide ant search - a recent model in ant optimization, heterogeneous sensitive a

A Langmuir study of novel Schiff Base ligand for ion sensor application

African Journals Online (AJOL)

The analysis made from extrapolating the П-A graphs led to the result of the estimated area and the radius of the ligand molecules oriented on the air-water subphase. The UV-Visible spectrometer was used to study the optical properties of the ligands. This study was made in order to recognize the fundamental properties of ...

Architecture effects on multivalent interactions by polypeptide-based multivalent ligands

Science.gov (United States)

Liu, Shuang

protein materials, including structural as well as functional proteins. Therefore, polypeptide-based multivalent scaffolds are used to display ligands to assess the contribution of different architectural parameters to the multivalent binding events. In this work, a family of alanine-rich alpha-helical glycopolypeptides was designed and synthesized by a combination of protein engineering and chemical coupling, to display two types of saccharide ligands for two different multivalent binding systems. The valencies, chain length and spacing between adjacent ligands of these multivalent ligands were designed in order to study architecture effects on multivalent interactions. The polypeptides and their glycoconjugates were characterized via various methods, including SDS-PAGE, NMR, HPLC, amino acid analysis (AAA), MALDI, circular dichroism (CD) and GPC. In the first multivalent binding system, cholera toxin B pentamer (CT B5) was chosen to be the protein receptor due to its well-characterized structure, lack of significant steric interference of binding to multiple binding sites, and requirement of only simple monosaccharide as ligands. Galactopyranoside was incorporated into polypeptide scaffolds through amine-carboxylic acid coupling to the side chains of glutamic acid residues. The inhibition and binding to CT B5 of these glycopolypeptide ligands were evaluated by direct enzyme-linked assay (DELA). As a complement method, weak affinity chromatography (WAC) was also used to evaluate glycopolypeptides binding to a CT B5 immobilized column. The architecture effects on CT B 5 inhibition are discussed. In the second system, cell surface receptor L-selectin was targeted by polypeptide-based multivalent ligands containing disulfated galactopyranoside ligands, due to its important roles in various immunological activities. The effects of glycopolypeptide architectural variables L-selectin shedding were evaluated via ELISA-based assays. These polypeptide-based multivalent ligands

Ligand pose and orientational sampling in molecular docking.

Directory of Open Access Journals (Sweden)

Ryan G Coleman

Full Text Available Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes. As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing. Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations. This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program. This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys-Enhanced (DUD-E benchmarking set, at multiple levels of sampling. Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20,000 molecular orientations in the binding site (and so from about 1×10(10 to 4×10(10 to 1×10(11 to 2×10(11 to 5×10(11 mean atoms scored per target, since multiple conformations are sampled per orientation, the enrichment of ligands over decoys monotonically increases for most DUD-E targets. Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values. Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field.

Training mechanical engineering students to utilize biological inspiration during product development.

Science.gov (United States)

Bruck, Hugh A; Gershon, Alan L; Golden, Ira; Gupta, Satyandra K; Gyger, Lawrence S; Magrab, Edward B; Spranklin, Brent W

2007-12-01

The use of bio-inspiration for the development of new products and devices requires new educational tools for students consisting of appropriate design and manufacturing technologies, as well as curriculum. At the University of Maryland, new educational tools have been developed that introduce bio-inspired product realization to undergraduate mechanical engineering students. These tools include the development of a bio-inspired design repository, a concurrent fabrication and assembly manufacturing technology, a series of undergraduate curriculum modules and a new senior elective in the bio-inspired robotics area. This paper first presents an overview of the two new design and manufacturing technologies that enable students to realize bio-inspired products, and describes how these technologies are integrated into the undergraduate educational experience. Then, the undergraduate curriculum modules are presented, which provide students with the fundamental design and manufacturing principles needed to support bio-inspired product and device development. Finally, an elective bio-inspired robotics project course is present, which provides undergraduates with the opportunity to demonstrate the application of the knowledge acquired through the curriculum modules in their senior year using the new design and manufacturing technologies.

Drawing inspiration from biological optical systems

Science.gov (United States)

Wolpert, H. D.

2009-08-01

Bio-Mimicking/Bio-Inspiration: How can we not be inspired by Nature? Life has evolved on earth over the last 3.5 to 4 billion years. Materials formed during this time were not toxic; they were created at low temperatures and low pressures unlike many of the materials developed today. The natural materials formed are self-assembled, multifunctional, nonlinear, complex, adaptive, self-repairing and biodegradable. The designs that failed are fossils. Those that survived are the success stories. Natural materials are mostly formed from organics, inorganic crystals and amorphous phases. The materials make economic sense by optimizing the design of the structures or systems to meet multiple needs. We constantly "see" many similar strategies in approaches, between man and nature, but we seldom look at the details of natures approaches. The power of image processing, in many of natures creatures, is a detail that is often overlooked. Seldon does the engineer interact with the biologist and learn what nature has to teach us. The variety and complexity of biological materials and the optical systems formed should inspire us.

Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates

International Nuclear Information System (INIS)

Dadachova, E.; Chappell, L.L.; Brechbiel, M.W.

1999-01-01

A simple spectrophotometric assay for determination of bifunctional polyazacarboxylate-macrocyclic ligands of different sizes that are conjugated to proteins has been developed for: 12-membered macrocycle DOTA (2-[4-nitrobenzyl]-1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) and analogs, the 15-membered PEPA macrocycle (2-[4-nitrobenzyl]-1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N'''' -pentaacetic acid), and the large 18-membered macrocycle HEHA (1,4,7,10,13,16-hexaazacyclooctadecane-N,N',N'',N''',N''''-hexaacetic acid). The method is based on titration of the blue-colored 1:1 Pb(II)-Arsenazo III (AAIII) complex with the polyazacarboxylate macrocyclic ligand in the concentration range of 0-2.5 μM, wherein color change occurring upon transchelation of the Pb(II) from the AAIII to the polyazamacrocyclic ligand is monitored at 656 nm. The assay is performed at ambient temperature within 20 min without any interfering interaction between the protein and Pb(II)-AA(III) complex. Thus, this method also provides a ligand-to-protein ratio (L/P ratio) that reflects the effective number of ligands per protein molecule available to radiolabeling. The method is not suitable for 14-membered TETA macrocycle (2-[4-nitrobenzyl]-1, 4, 8, 11-tetraazacyclotetradecane N,N',N'',N'''-tetraacetic acid) because of low stability constant of Pb(II)-TETA complex. The method is rapid, simple and may be customized for other polyazacarboxylate macrocyclic ligands

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis.

Science.gov (United States)

Pawlowski, Christa L; Li, Wei; Sun, Michael; Ravichandran, Kavya; Hickman, DaShawn; Kos, Clarissa; Kaur, Gurbani; Sen Gupta, Anirban

2017-06-01

Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIIb-IIIa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A 2 . Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment. Copyright © 2017. Published by Elsevier Ltd.

Rosetta Ligand docking with flexible XML protocols.

Science.gov (United States)

Lemmon, Gordon; Meiler, Jens

2012-01-01

RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

DEFF Research Database (Denmark)

Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

2004-01-01

binding to SRCR domain 3 exhibited effective inhibition of ligand binding. Furthermore, analysis of purified native CD163 revealed that proteolytic cleavage in SRCR domain 3 inactivates ligand binding. Calcium protects against cleavage in this domain. Analysis of the calcium sensitivity of ligand binding...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...... for the calcium-sensitive coupling of haptoglobin.hemoglobin complexes....

Ligand-receptor Interactions by NMR Spectroscopy

Directory of Open Access Journals (Sweden)

Novak. P.

2008-04-01

Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

Analysis of TNF-related apoptosis-inducing ligand and receptors and implications in thymus biology and myasthenia gravis.

Science.gov (United States)

Kanatli, Irem; Akkaya, Bahar; Uysal, Hilmi; Kahraman, Sevim; Sanlioglu, Ahter Dilsad

2017-02-01

Myasthenia Gravis is an autoantibody-mediated, neuromuscular junction disease, and is usually associated with thymic abnormalities presented as thymic tumors (~10%) or hyperplastic thymus (~65%). The exact role of thymus in Myasthenia Gravis development is not clear, yet many patients benefit from thymectomy. The apoptotic ligand TNF-Related Apoptosis-Inducing Ligand is thought to be involved in the regulation of thymocyte counts, although conflicting results are reported. We investigated differential expression profiles of TNF-Related Apoptosis-Inducing Ligand and its transmembrane receptors, Nuclear Factor-kB activation status, and apoptotic cell counts in healthy thymic tissue and pathological thymus from Myasthenia Gravis patients. All tissues expressed TNF-Related Apoptosis-Inducing Ligand and its receptors, with hyperplastic tissue having the highest expression levels of death receptors DR4 and DR5. No detectable Nuclear Factor-kB activation, at least via the canonical Protein Kinase A-mediated p65 Ser276 phosphorylation, was evident in any of the tissues studied. Apoptotic cell counts were higher in MG-associated tissue compared to the normal thymus. Possible use of the TNF-Related Apoptosis-Inducing Ligand within the concept of an apoptotic ligand-mediated medical thymectomy in thymoma- or thymic hyperplasia-associated Myasthenia Gravis is also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

New generation of docking programs: Supercomputer validation of force fields and quantum-chemical methods for docking.

Science.gov (United States)

Sulimov, Alexey V; Kutov, Danil C; Katkova, Ekaterina V; Ilin, Ivan S; Sulimov, Vladimir B

2017-11-01

Discovery of new inhibitors of the protein associated with a given disease is the initial and most important stage of the whole process of the rational development of new pharmaceutical substances. New inhibitors block the active site of the target protein and the disease is cured. Computer-aided molecular modeling can considerably increase effectiveness of new inhibitors development. Reliable predictions of the target protein inhibition by a small molecule, ligand, is defined by the accuracy of docking programs. Such programs position a ligand in the target protein and estimate the protein-ligand binding energy. Positioning accuracy of modern docking programs is satisfactory. However, the accuracy of binding energy calculations is too low to predict good inhibitors. For effective application of docking programs to new inhibitors development the accuracy of binding energy calculations should be higher than 1kcal/mol. Reasons of limited accuracy of modern docking programs are discussed. One of the most important aspects limiting this accuracy is imperfection of protein-ligand energy calculations. Results of supercomputer validation of several force fields and quantum-chemical methods for docking are presented. The validation was performed by quasi-docking as follows. First, the low energy minima spectra of 16 protein-ligand complexes were found by exhaustive minima search in the MMFF94 force field. Second, energies of the lowest 8192 minima are recalculated with CHARMM force field and PM6-D3H4X and PM7 quantum-chemical methods for each complex. The analysis of minima energies reveals the docking positioning accuracies of the PM7 and PM6-D3H4X quantum-chemical methods and the CHARMM force field are close to one another and they are better than the positioning accuracy of the MMFF94 force field. Copyright © 2017 Elsevier Inc. All rights reserved.

Bio-inspired Edible Superhydrophobic Interface for Reducing Residual Liquid Food.

Science.gov (United States)

Li, Yao; Bi, Jingran; Wang, Siqi; Zhang, Tan; Xu, Xiaomeng; Wang, Haitao; Cheng, Shasha; Zhu, Bei-Wei; Tan, Mingqian

2018-03-07

Significant wastage of residual liquid food, such as milk, yogurt, and honey, in food containers has attracted great attention. In this work, a bio-inspired edible superhydrophobic interface was fabricated using U.S. Food and Drug Administration-approved and edible honeycomb wax, arabic gum, and gelatin by a simple and low-cost method. The bio-inspired edible superhydrophobic interface showed multiscale structures, which were similar to that of a lotus leaf surface. This bio-inspired edible superhydrophobic interface displayed high contact angles for a variety of liquid foods, and the residue of liquid foods could be effectively reduced using the bio-inspired interface. To improve the adhesive force of the superhydrophobic interface, a flexible edible elastic film was fabricated between the interface and substrate material. After repeated folding and flushing for a long time, the interface still maintained excellent superhydrophobic property. The bio-inspired edible superhydrophobic interface showed good biocompatibility, which may have potential applications as a functional packaging interface material.

A method for fast energy estimation and visualization of protein-ligand interaction

Science.gov (United States)

Tomioka, Nobuo; Itai, Akiko; Iitaka, Yoichi

1987-10-01

A new computational and graphical method for facilitating ligand-protein docking studies is developed on a three-dimensional computer graphics display. Various physical and chemical properties inside the ligand binding pocket of a receptor protein, whose structure is elucidated by X-ray crystal analysis, are calculated on three-dimensional grid points and are stored in advance. By utilizing those tabulated data, it is possible to estimate the non-bonded and electrostatic interaction energy and the number of possible hydrogen bonds between protein and ligand molecules in real time during an interactive docking operation. The method also provides a comprehensive visualization of the local environment inside the binding pocket. With this method, it becomes easier to find a roughly stable geometry of ligand molecules, and one can therefore make a rapid survey of the binding capability of many drug candidates. The method will be useful for drug design as well as for the examination of protein-ligand interactions.

Custom Coordination Environments for Lanthanoids: Tripodal Ligands Achieve Near-Perfect Octahedral Coordination for Two Dysprosium-Based Molecular Nanomagnets.

Science.gov (United States)

Lim, Kwang Soo; Baldoví, José J; Jiang, ShangDa; Koo, Bong Ho; Kang, Dong Won; Lee, Woo Ram; Koh, Eui Kwan; Gaita-Ariño, Alejandro; Coronado, Eugenio; Slota, Michael; Bogani, Lapo; Hong, Chang Seop

2017-05-01

Controlling the coordination sphere of lanthanoid complexes is a challenging critical step toward controlling their relaxation properties. Here we present the synthesis of hexacoordinated dysprosium single-molecule magnets, where tripodal ligands achieve a near-perfect octahedral coordination. We perform a complete experimental and theoretical investigation of their magnetic properties, including a full single-crystal magnetic anisotropy analysis. The combination of electrostatic and crystal-field computational tools (SIMPRE and CONDON codes) allows us to explain the static behavior of these systems in detail.

Exploring the composition of protein-ligand binding sites on a large scale.

Directory of Open Access Journals (Sweden)

Nickolay A Khazanov

Full Text Available The residue composition of a ligand binding site determines the interactions available for diffusion-mediated ligand binding, and understanding general composition of these sites is of great importance if we are to gain insight into the functional diversity of the proteome. Many structure-based drug design methods utilize such heuristic information for improving prediction or characterization of ligand-binding sites in proteins of unknown function. The Binding MOAD database if one of the largest curated sets of protein-ligand complexes, and provides a source of diverse, high-quality data for establishing general trends of residue composition from currently available protein structures. We present an analysis of 3,295 non-redundant proteins with 9,114 non-redundant binding sites to identify residues over-represented in binding regions versus the rest of the protein surface. The Binding MOAD database delineates biologically-relevant "valid" ligands from "invalid" small-molecule ligands bound to the protein. Invalids are present in the crystallization medium and serve no known biological function. Contacts are found to differ between these classes of ligands, indicating that residue composition of biologically relevant binding sites is distinct not only from the rest of the protein surface, but also from surface regions capable of opportunistic binding of non-functional small molecules. To confirm these trends, we perform a rigorous analysis of the variation of residue propensity with respect to the size of the dataset and the content bias inherent in structure sets obtained from a large protein structure database. The optimal size of the dataset for establishing general trends of residue propensities, as well as strategies for assessing the significance of such trends, are suggested for future studies of binding-site composition.

InSpiRe - Intelligent Spine Rehabilitation

DEFF Research Database (Denmark)

Bøg, Kasper Hafstrøm; Helms, Niels Henrik; Kjær, Per

Rapport on InSpiRe-projektet: InSpiRe er et nationalt netværk, der skal fremme mulighederne for intelligent genoptræning i forhold til ryglidelser. I netværket mødes forskere, virksomheder, kiropraktorer og fysioterapeuter for at udvikle nye genoptrænings og/eller behandlingsteknologier.......Rapport on InSpiRe-projektet: InSpiRe er et nationalt netværk, der skal fremme mulighederne for intelligent genoptræning i forhold til ryglidelser. I netværket mødes forskere, virksomheder, kiropraktorer og fysioterapeuter for at udvikle nye genoptrænings og/eller behandlingsteknologier....

LEGO-inspired drug design

DEFF Research Database (Denmark)

Thanh Tung, Truong; Dao, Trong Tuan; Grifell Junyent, Marta

2018-01-01

The fungal plasma membrane H+-ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure-activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for design...

Three-Dimensional-Printing of Bio-Inspired Composites

Science.gov (United States)

Xiang Gu, Grace; Su, Isabelle; Sharma, Shruti; Voros, Jamie L.; Qin, Zhao; Buehler, Markus J.

2016-01-01

Optimized for millions of years, natural materials often outperform synthetic materials due to their hierarchical structures and multifunctional abilities. They usually feature a complex architecture that consists of simple building blocks. Indeed, many natural materials such as bone, nacre, hair, and spider silk, have outstanding material properties, making them applicable to engineering applications that may require both mechanical resilience and environmental compatibility. However, such natural materials are very difficult to harvest in bulk, and may be toxic in the way they occur naturally, and therefore, it is critical to use alternative methods to fabricate materials that have material functions similar to material function as their natural counterparts for large-scale applications. Recent progress in additive manufacturing, especially the ability to print multiple materials at upper micrometer resolution, has given researchers an excellent instrument to design and reconstruct natural-inspired materials. The most advanced 3D-printer can now be used to manufacture samples to emulate their geometry and material composition with high fidelity. Its capabilities, in combination with computational modeling, have provided us even more opportunities for designing, optimizing, and testing the function of composite materials, in order to achieve composites of high mechanical resilience and reliability. In this review article, we focus on the advanced material properties of several multifunctional biological materials and discuss how the advanced 3D-printing techniques can be used to mimic their architectures and functions. Lastly, we discuss the limitations of 3D-printing, suggest possible future developments, and discuss applications using bio-inspired materials as a tool in bioengineering and other fields. PMID:26747791

Three-Dimensional-Printing of Bio-Inspired Composites.

Science.gov (United States)

Xiang Gu, Grace; Su, Isabelle; Sharma, Shruti; Voros, Jamie L; Qin, Zhao; Buehler, Markus J

2016-02-01

Optimized for millions of years, natural materials often outperform synthetic materials due to their hierarchical structures and multifunctional abilities. They usually feature a complex architecture that consists of simple building blocks. Indeed, many natural materials such as bone, nacre, hair, and spider silk, have outstanding material properties, making them applicable to engineering applications that may require both mechanical resilience and environmental compatibility. However, such natural materials are very difficult to harvest in bulk, and may be toxic in the way they occur naturally, and therefore, it is critical to use alternative methods to fabricate materials that have material functions similar to material function as their natural counterparts for large-scale applications. Recent progress in additive manufacturing, especially the ability to print multiple materials at upper micrometer resolution, has given researchers an excellent instrument to design and reconstruct natural-inspired materials. The most advanced 3D-printer can now be used to manufacture samples to emulate their geometry and material composition with high fidelity. Its capabilities, in combination with computational modeling, have provided us even more opportunities for designing, optimizing, and testing the function of composite materials, in order to achieve composites of high mechanical resilience and reliability. In this review article, we focus on the advanced material properties of several multifunctional biological materials and discuss how the advanced 3D-printing techniques can be used to mimic their architectures and functions. Lastly, we discuss the limitations of 3D-printing, suggest possible future developments, and discuss applications using bio-inspired materials as a tool in bioengineering and other fields.

Inspiration from drones, Lidar measurements and 3D models in undergraduate teaching

Science.gov (United States)

Blenkinsop, Thomas; Ellis, Jennifer

2017-04-01

Three-dimensional models, photogrammetry and remote sensing are increasingly common techniques used in structural analysis. We have found that using drones and Lidar on undergraduate field trips has piqued interest in fieldwork, provided data for follow-up laboratory exercises, and inspired undergraduates to attempt 3D modelling in independent mapping projects. The scale of structures visible in cliff and sea shore exposures in South Wales is ideal for using drones to capture images for 3D models. Fault scarps in the South Wales coalfield were scanned by Lidar and drone. Our experience suggests that the drone data were much easier to acquire and process than the Lidar data, and adequate for most teaching purposes. In the lab, we used the models to show the structure in 3D, and as the basis for an introduction to geological modelling software. Now that tools for photogrammetry, drones, and processing software are widely available and affordable, they can be readily integrated into teaching. An additional benefit from the images and models is that they may be used for exercises that can be substituted for fieldwork to achieve some (but not all) of the learning outcomes in the case that field access is prevented.

A chemometric analysis of ligand-induced changes in intrinsic fluorescence of folate binding protein indicates a link between altered conformational structure and physico-chemical characteristics

DEFF Research Database (Denmark)

Bruun, Susanne W; Holm, Jan; Hansen, Steen Ingemann

2009-01-01

Ligand binding alters the conformational structure and physico-chemical characteristics of bovine folate binding protein (FBP). For the purpose of achieving further information we analyzed ligand (folate and methotrexate)-induced changes in the fluorescence landscape of FBP. Fluorescence excitation...... of folate accords fairly well with the disappearance of strongly hydrophobic tryptophan residues from the solvent-exposed surface of FBP. The PARAFAC has thus proven useful to establish a hitherto unexplained link between parallel changes in conformational structure and physico-chemical characteristics...... of FBP induced by folate binding. Parameters for ligand binding derived from PARAFAC analysis of the fluorescence data were qualitatively and quantitatively similar to those obtained from binding of radiofolate to FBP. Herein, methotrexate exhibited a higher affinity for FBP than in competition...

Inspirational Catalogue of Master Thesis Proposals 2015

DEFF Research Database (Denmark)

Thorndahl, Søren

2015-01-01

This catalog presents different topics for master thesis projects. It is important to emphasize that the project descriptions only serves as an inspiration and that you always can discuss with the potential supervisors the specific contents of a project.......This catalog presents different topics for master thesis projects. It is important to emphasize that the project descriptions only serves as an inspiration and that you always can discuss with the potential supervisors the specific contents of a project....

A Ferrocene-Based Catecholamide Ligand: the Consequences of Ligand Swivel for Directed Supramolecular Self-Assembly

Energy Technology Data Exchange (ETDEWEB)

Mugridge, Jeffrey; Fiedler, Dorothea; Raymond, Kenneth

2010-02-04

A ferrocene-based biscatecholamide ligand was prepared and investigated for the formation of metal-ligand supramolecular assemblies with different metals. Reaction with Ge(IV) resulted in the formation of a variety of Ge{sub n}L{sub m} coordination complexes, including [Ge{sub 2}L{sub 3}]{sup 4-} and [Ge{sub 2}L{sub 2}({mu}-OMe){sub 2}]{sup 2-}. The ligand's ability to swivel about the ferrocenyl linker and adopt different conformations accounts for formation of many different Ge{sub n}L{sub m} species. This study demonstrates why conformational ligand rigidity is essential in the rational design and directed self-assembly of supramolecular complexes.

Nature-inspired design of hybrid intelligent systems

CERN Document Server

Castillo, Oscar; Kacprzyk, Janusz

2017-01-01

This book highlights recent advances in the design of hybrid intelligent systems based on nature-inspired optimization and their application in areas such as intelligent control and robotics, pattern recognition, time series prediction, and optimization of complex problems. The book is divided into seven main parts, the first of which addresses theoretical aspects of and new concepts and algorithms based on type-2 and intuitionistic fuzzy logic systems. The second part focuses on neural network theory, and explores the applications of neural networks in diverse areas, such as time series prediction and pattern recognition. The book’s third part presents enhancements to meta-heuristics based on fuzzy logic techniques and describes new nature-inspired optimization algorithms that employ fuzzy dynamic adaptation of parameters, while the fourth part presents diverse applications of nature-inspired optimization algorithms. In turn, the fifth part investigates applications of fuzzy logic in diverse areas, such as...

Traceability investigation in Computed Tomography using industry-inspired workpieces

DEFF Research Database (Denmark)

Kraemer, Alexandra; Stolfi, Alessandro; Schneider, Timm

2017-01-01

This paper concerns an investigation of the accuracy of Computed Tomography (CT) measurements using four industry-inspired workpieces. A total of 16 measurands were selected and calibrated using CMMs. CT measurements on industry-inspired workpieces were carried out using two CTs having different...

Macrocyclic G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, M C; Ulven, Trond

2010-01-01

are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

Structural and Electrochemical Consequences of [Cp*] Ligand Protonation.

Science.gov (United States)

Peng, Yun; Ramos-Garcés, Mario V; Lionetti, Davide; Blakemore, James D

2017-09-05

There are few examples of the isolation of analogous metal complexes bearing [η 5 -Cp*] and [η 4 -Cp*H] (Cp* = pentamethylcyclopentadienyl) complexes within the same metal/ligand framework, despite the relevance of such structures to catalytic applications. Recently, protonation of Cp*Rh(bpy) (bpy = 2,2'-bipyridyl) has been shown to yield a complex bearing the uncommon [η 4 -Cp*H] ligand, rather than generating a [Rh III -H] complex. We now report the purification and isolation of this protonated species, as well as characterization of analogous complexes of 1,10-phenanthroline (phen). Specifically, reaction of Cp*Rh(bpy) or Cp*Rh(phen) with 1 equiv of Et 3 NH + Br - affords rhodium compounds bearing endo-η 4 -pentamethylcyclopentadiene (η 4 -Cp*H) as a ligand. NMR spectroscopy and single-crystal X-ray diffraction studies confirm protonation of the Cp* ligand, rather than formation of metal hydride complexes. Analysis of new structural data and electronic spectra suggests that phen is significantly reduced in Cp*Rh(phen), similar to the case of Cp*Rh(bpy). Backbonding interactions with olefinic motifs are activated by formation of [η 4 -Cp*H]; protonation of [Cp*] stabilizes the low-valent metal center and results in loss of reduced character on the diimine ligands. In accord with these changes in electronic structure, electrochemical studies reveal a distinct manifold of redox processes that are accessible in the [Cp*H] complexes in comparison with their [Cp*] analogues; these processes suggest new applications in catalysis for the complexes bearing endo-η 4 -Cp*H.

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

International Nuclear Information System (INIS)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei

2015-01-01

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H_2ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H_2hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd_2(2,6-ndc)_2(bpp)(DMF)]·2DMF (1) and [Cd_3(hmdb)_3(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

Energy Technology Data Exchange (ETDEWEB)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei, E-mail: hanlei@nbu.edu.cn

2015-12-15

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

Cell surface receptors for signal transduction and ligand transport: a design principles study.

Directory of Open Access Journals (Sweden)

Harish Shankaran

2007-06-01

Full Text Available Receptors constitute the interface of cells to their external environment. These molecules bind specific ligands involved in multiple processes, such as signal transduction and nutrient transport. Although a variety of cell surface receptors undergo endocytosis, the systems-level design principles that govern the evolution of receptor trafficking dynamics are far from fully understood. We have constructed a generalized mathematical model of receptor-ligand binding and internalization to understand how receptor internalization dynamics encodes receptor function and regulation. A given signaling or transport receptor system represents a particular implementation of this module with a specific set of kinetic parameters. Parametric analysis of the response of receptor systems to ligand inputs reveals that receptor systems can be characterized as being: i avidity-controlled where the response control depends primarily on the extracellular ligand capture efficiency, ii consumption-controlled where the ability to internalize surface-bound ligand is the primary control parameter, and iii dual-sensitivity where both the avidity and consumption parameters are important. We show that the transferrin and low-density lipoprotein receptors are avidity-controlled, the vitellogenin receptor is consumption-controlled, and the epidermal growth factor receptor is a dual-sensitivity receptor. Significantly, we show that ligand-induced endocytosis is a mechanism to enhance the accuracy of signaling receptors rather than merely serving to attenuate signaling. Our analysis reveals that the location of a receptor system in the avidity-consumption parameter space can be used to understand both its function and its regulation.

Bio-inspired hydrophobic modification of cellulose nanocrystals with castor oil.

Science.gov (United States)

Shang, Qianqian; Liu, Chengguo; Hu, Yun; Jia, Puyou; Hu, Lihong; Zhou, Yonghong

2018-07-01

This work presents an efficient and environmentally friendly approach to generate hydrophobic cellulose nanocrystals (CNC) using thiol-containing castor oil (CO-SH) as a renewable hydrophobe with the assist of bio-inspired dopamine at room temperature. The modification process included the formation of the polydopamine (PDA) buffer layer on CNC surfaces and the Michael addition reaction between the catechol moieties of PDA coating and thiol groups of CO-SH. The morphology, crystalline structure, surface chemistry, thermal stability and hydrophobicity of the modified CNC were charactered by TEM, XRD, FT-IR, solid-state 13 C NMR, XPS, TGA and contact angle analysis. The modified CNC preserved cellulose crystallinity, displayed higher thermal stability than unmodified CNC, and was highly hydrophobic with a water contact angle of 95.6°. The simplicity and versatility of the surface modification strategy inspired by adhesive protein of mussel may promote rapid development of hydrophobic bio-based nanomaterials for various applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Highly efficient bioinspired molecular Ru water oxidation catalysts with negatively charged backbone ligands.

Science.gov (United States)

Duan, Lele; Wang, Lei; Li, Fusheng; Li, Fei; Sun, Licheng

2015-07-21

The oxygen evolving complex (OEC) of the natural photosynthesis system II (PSII) oxidizes water to produce oxygen and reducing equivalents (protons and electrons). The oxygen released from PSII provides the oxygen source of our atmosphere; the reducing equivalents are used to reduce carbon dioxide to organic products, which support almost all organisms on the Earth planet. The first photosynthetic organisms able to split water were proposed to be cyanobacteria-like ones appearing ca. 2.5 billion years ago. Since then, nature has chosen a sustainable way by using solar energy to develop itself. Inspired by nature, human beings started to mimic the functions of the natural photosynthesis system and proposed the concept of artificial photosynthesis (AP) with the view to creating energy-sustainable societies and reducing the impact on the Earth environments. Water oxidation is a highly energy demanding reaction and essential to produce reducing equivalents for fuel production, and thereby effective water oxidation catalysts (WOCs) are required to catalyze water oxidation and reduce the energy loss. X-ray crystallographic studies on PSII have revealed that the OEC consists of a Mn4CaO5 cluster surrounded by oxygen rich ligands, such as oxyl, oxo, and carboxylate ligands. These negatively charged, oxygen rich ligands strongly stabilize the high valent states of the Mn cluster and play vital roles in effective water oxidation catalysis with low overpotential. This Account describes our endeavors to design effective Ru WOCs with low overpotential, large turnover number, and high turnover frequency by introducing negatively charged ligands, such as carboxylate. Negatively charged ligands stabilized the high valent states of Ru catalysts, as evidenced by the low oxidation potentials. Meanwhile, the oxygen production rates of our Ru catalysts were improved dramatically as well. Thanks to the strong electron donation ability of carboxylate containing ligands, a seven

Mediating between the muse and the masses: inspiration and the actualization of creative ideas.

Science.gov (United States)

Thrash, Todd M; Maruskin, Laura A; Cassidy, Scott E; Fryer, James W; Ryan, Richard M

2010-03-01

Within the creativity domain, inspiration is a motivational state posited to energize the actualization of creative ideas. The authors examined the construct validity, predictive utility, and function of inspiration in the writing process. Study 1, a cross-lagged panel study, showed that getting creative ideas and being inspired are distinct and that the former precedes the latter. In Study 2, inspiration, at the between-person level, predicted the creativity of scientific writing, whereas effort predicted technical merit. Within persons, peaks in inspiration predicted peaks in creativity and troughs in technical merit. In Study 3, inspiration predicted the creativity of poetry. Consistent with its posited transmission function, inspiration mediated between creativity of the idea and creativity of the product, whereas effort, positive affect, and awe did not. Study 4 extended the Study 3 findings to fiction writing. Openness to aesthetics and positive affect predicted creativity of the idea, whereas approach temperament moderated the relation between creativity of the idea and inspiration. Inspiration predicted efficiency, productivity, and use of shorter words, indicating that inspiration not only transmits creativity but does so economically.

A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

Science.gov (United States)

Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

2014-01-01

Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

Secondary ligand-directed assembly of Co(II) coordination polymers based on a pyridine carboxylate ligand

International Nuclear Information System (INIS)

Cao, Ke-Li; Zhang, Yi-Ping; Cai, Yi-Ni; Xu, Xiao-Wei; Feng, Yun-Long

2014-01-01

To investigate the influence of hydrogen bonds and secondary ligands on the structures and properties of the resulting frameworks, five new Co(II) compounds have been synthesized by the reactions of Co(II) salts and 3,5-bis(pyridin-4-ylmethoxy)benzoic acid (HL) with four rationally selected dicarboxylic acid ligands. Without secondary ligand, we got one compound [CoL 2 (H 2 O) 2 ] n ·2nH 2 O (1), which possesses a 1D chain structure. In the presence of ancillary ligands, namely, 1,3-adamantanedicarboxylic acid (H 2 adbc), terephthalic acid (H 2 tpa), thiophene-2,5-dicarboxylic acid (H 2 tdc) and 1,4-benzenedithioacetic acid (H 2 bdtc), four 3D structures [Co 2 L 2 (adbc)] n ·nH 2 O (2), [Co 2 L 2 (tpa)] n (3), [Co 2 L 2 (tdc)] n (4), [Co 2 L 2 (bdtc)(H 2 O)] n (5) were obtained, respectively. It can be observed from the architectures of 1–5 that hydrogen bonds and secondary ligands both have great effects on the spatial connective fashions, resulting in the formation of various dimensional compounds. The XRPD, TGA data of title polymers and the magnetic properties for 2 and 5 have also been investigated. - Graphical abstract: The structural differences show that the ancillary ligands have great effects on the spatial connective fashions, resulting in the formation of various dimensional compounds. - Highlights: • Five new Co(II) coordination polymers have been synthesized by solvothermal reactions based on 3,5-bis(pyridin-4-ylmethoxy)benzoic acid (HL). • The long-flexible ligand (HL) is a good candidate to produce interpenetrating architectures. • The secondary dicarboxylic acid ligands play important roles in the spatial connective fashions and the formation of various dimensional compounds. • The magnetism studies show that both 2 and 5 exhibit antiferromagnetic interactions

Climate change in EIA - Inspiration from practice

DEFF Research Database (Denmark)

Larsen, Sanne Vammen

2013-01-01

Climate change integration has been a topic of much interest in the field of impact assessment for a period, and thus far quite some emphasis has been put on discussions of purpose, relevance and overall approaches in both Environmental Impact Assessment of projects (EIA) and Strategic Environmen......Climate change integration has been a topic of much interest in the field of impact assessment for a period, and thus far quite some emphasis has been put on discussions of purpose, relevance and overall approaches in both Environmental Impact Assessment of projects (EIA) and Strategic...... Environmental Assessments of plans and programmes (SEA). However, EIAs and SEAs are already being made, which integrate climate change, and for some aspects this practice has evolved over a long period. This paper seeks to explore this practice and find inspiration from the work with climate change already...... taking place. For exploring the praxis of integrating climate change in practice a document study of 100 Danish EIA reports is carried out. From these reports, statistics and examples are drawn. The study shows an emphasis on integration of climate change mitigation, using various quantitative tools...

Supersymmetric SO(10) models inspired by deconstruction

International Nuclear Information System (INIS)

Huang Chaoshang; Jiang Jing; Li Tianjun

2004-01-01

We consider 4-dimensional N=1 supersymmetric SO(10) models inspired by deconstruction of 5-dimensional N=1 supersymmetric orbifold SO(10) models and high-dimensional non-supersymmetric SO(10) models with Wilson line gauge symmetry breaking. We discuss the SO(10)xSO(10) models with bi-fundamental link fields where the gauge symmetry can be broken down to the Pati-Salam, SU(5)xU(1), flipped SU(5)xU(1)' or the Standard Model like gauge symmetry. We also propose an SO(10)xSO(6)xSO(4) model with bi-fundamental link fields where the gauge symmetry is broken down to the Pati-Salam gauge symmetry, and an SO(10)xSO(10) model with bi-spinor link fields where the gauge symmetry is broken down to the flipped SU(5)xU(1)' gauge symmetry. In these two models, the Pati-Salam and flipped SU(5)xU(1)' gauge symmetry can be further broken down to the Standard Model gauge symmetry, the doublet-triplet splittings can be obtained by the missing partner mechanism, and the proton decay problem can be solved. We also study the gauge coupling unification. We briefly comment on the interesting variation models with gauge groups SO(10)xSO(6) and SO(10)xflippedSU(5)xU(1)' in which the proton decay problem can be solved

Ligands Exchange Process on Gold Nanoparticles in Acetone Solution

Science.gov (United States)

Hu, C. L.; Mu, Y. Y.; Bian, Z. C.; Luo, Z. H.; Luo, K.; Huang, A. Z.

2018-05-01

The ligands exchange process on gold nanoparticles (GNPs) was proceeded by using hydrophobic group (PPh3) and hydrophilic group (THPO) in acetone solution. The FTIR and XPS results demonstrated that part of THPO was replaced by PPh3 which was dissolved in polar solution (acetone); the results were in accordance with the electrochemical analysis where the differential capacity decreased with increasing exchange time. After 12 h, the exchange process terminated and the final ratio of PPh3 and THPO was about 1.4: 1. This ratio remained unchanged although the PPh3 and THPO modified GNPs re-dispersed in the PPh3 acetone solution demonstrating the stable adsorption of both ligands after exchanging for 12 h. The TEM images showed that the gold nanoparticles were self-assembled from scattered to arranged morphology due to the existence of hydrophilic and hydrophobic ligands and led to Janus gold nanoparticles.

Dynamics Analysis of Fluid-Structure Interaction for a Biologically-Inspired Biped Robot Running on Water

Directory of Open Access Journals (Sweden)

Linsen Xu

2013-10-01

Full Text Available A kinematics analysis of a biologically-inspired biped robot is carried out, and the trajectory of the robot foot is understood. For calculating the pressure distribution across a robot foot before touching the surface of water, the compression flow of air and the depression motion of the water surface are considered. The pressure model after touching the water surface has been built according to the theory of rigid body planar motion. The multi-material ALE algorithm is applied to emulate the course of the foot slapping water. The simulation results indicate that the model of the bionic robot can satisfy the water-running function. The real prototype of the robot is manufactured to test its function of running on water. When the biped robot is running on water, the average force generated by the propulsion mechanism is about 1.3N. The experimental results show that the propulsion system can satisfy the requirement of biped robot running on water.

Origami-Inspired Folding of Thick, Rigid Panels

Science.gov (United States)

Trease, Brian P.; Thomson, Mark W.; Sigel, Deborah A.; Walkemeyer, Phillip E.; Zirbel, Shannon; Howell, Larry; Lang, Robert

2014-01-01

To achieve power of 250 kW or greater, a large compression ratio of stowed-to-deployed area is needed. Origami folding patterns were used to inspire the folding of a solar array to achieve synchronous deployment; however, origami models are generally created for near-zero-thickness material. Panel thickness is one of the main challenges of origami-inspired design. Three origami-inspired folding techniques (flasher, square twist, and map fold) were created with rigid panels and hinges. Hinge components are added to the model to enable folding of thick, rigid materials. Origami models are created assuming zero (or near zero) thickness. When a material with finite thickness is used, the panels are required to bend around an increasingly thick fold as they move away from the center of the model. The two approaches for dealing with material thickness are to use membrane hinges to connect the panels, or to add panel hinges, or hinges of the same thickness, at an appropriate width to enable folding.

Squid-inspired vehicle design using coupled fluid-solid analytical modeling

Science.gov (United States)

Giorgio-Serchi, Francesco; Weymouth, Gabriel

2017-11-01

The need for enhanced automation in the marine and maritime fields is fostering research into robust and highly maneuverable autonomous underwater vehicles. To address these needs we develop design principles for a new generation of soft-bodied aquatic vehicles similar to octopi and squids. In particular, we consider the capability of pulsed-jetting bodies to boost thrust by actively modifying their external body-shape and in this way benefit of the contribution from added-mass variation. We present an analytical formulation of the coupled fluid-structure interaction between the elastic body and the ambient fluid. The model incorporates a number of new salient contributions to the soft-body dynamics. We highlight the role of added-mass variation effects of the external fluid in enhancing thrust and assess how the shape-changing actuation is impeded by a confinement-related unsteady inertial term and by an external shape-dependent fluid stiffness contribution. We show how the analysis of these combined terms has guided us to the design of a new prototype of a squid-inspired vehicle tuning of the natural frequency of the coupled fluid-solid system with the purpose of optimizing its actuation routine.

Trapping of palindromic ligands within native transthyretin prevents amyloid formation

Science.gov (United States)

Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.; Robinson, Carol V.; Wood, Stephen P.; Pepys, Mark B.

2010-01-01

Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis. PMID:21059958

Application of rank annihilation factor analysis to the spectrophotometric determination of the formation constant of complex of a new synthesized tripodal ligand with Co2+

Directory of Open Access Journals (Sweden)

Reza Golbedaghi

2017-05-01

Full Text Available The complex formation between a new synthesized tripodal ligand (L22py and the cation Co2+ in water was studied spectrophotometrically using rank annihilation factor analysis (RAFA. According to molar ratio data the stoichiometry of complexation between the ligand and the cation Co2+ was 1:1. Formation constant of this complex was derived using RAFA on spectrophotometric data. In this process the contribution of ligand is removed from the absorbance data matrix when the complex stability constant acts as an optimizing object and simply combined with the pure spectrum of ligand, the rank of original data matrix can be reduced by one by annihilating the information of the ligand from the original data matrix. The effect of ethanol, dimethylformamide (DMF and acetonitrile (AN was investigated on the formation constant of the Co2+ complex. Complex formation constant in water was estimated as log Kf = 5.09 ± 0.02. In mixtures of solvents of water and DMF and water and AN, the formation constant of the complex was increased because of lowering donor number of the solvent and in mixture of water and ethanol, the complex formation constant was decreased because of lowering of dielectric constant of the solvent.

Bio-inspired ciliary force sensor for robotic platforms

KAUST Repository

Ribeiro, Pedro; Khan, Mohammed Asadullah; Alfadhel, Ahmed; Kosel, Jü rgen; Franco, Fernando; Cardoso, Susana; Bernardino, Alexandre; Schmitz, Alexander; Santos-Victor, Jose; Jamone, Lorenzo

2017-01-01

The detection of small forces is of great interest in any robotic application that involves interaction with the environment (e.g., objects manipulation, physical human-robot interaction, minimally invasive surgery), since it allows the robot to detect the contacts early on and to act accordingly. In this letter, we present a sensor design inspired by the ciliary structure frequently found in nature, consisting of an array of permanently magnetized cylinders (cilia) patterned over a giant magnetoresistance sensor (GMR). When these cylinders are deformed in shape due to applied forces, the stray magnetic field variation will change the GMR sensor resistivity, thus enabling the electrical measurement of the applied force. In this letter, we present two 3 mm × 3 mm prototypes composed of an array of five cilia with 1 mm of height and 120 and 200 μm of diameter for each prototype. A minimum force of 333 μN was measured. A simulation model for determining the magnetized cylinders average stray magnetic field is also presented.

Bio-inspired ciliary force sensor for robotic platforms

KAUST Repository

Ribeiro, Pedro

2017-01-20

The detection of small forces is of great interest in any robotic application that involves interaction with the environment (e.g., objects manipulation, physical human-robot interaction, minimally invasive surgery), since it allows the robot to detect the contacts early on and to act accordingly. In this letter, we present a sensor design inspired by the ciliary structure frequently found in nature, consisting of an array of permanently magnetized cylinders (cilia) patterned over a giant magnetoresistance sensor (GMR). When these cylinders are deformed in shape due to applied forces, the stray magnetic field variation will change the GMR sensor resistivity, thus enabling the electrical measurement of the applied force. In this letter, we present two 3 mm × 3 mm prototypes composed of an array of five cilia with 1 mm of height and 120 and 200 μm of diameter for each prototype. A minimum force of 333 μN was measured. A simulation model for determining the magnetized cylinders average stray magnetic field is also presented.

Multi-structure docking analysis of BACE1 crystal structures and non-peptidic ligands.

Science.gov (United States)

Haghighijoo, Zahra; Hemmateenejad, Bahram; Edraki, Najmeh; Miri, Ramin; Emami, Saeed

2017-09-01

In order to design novel non-peptidic inhibitors of BACE1, many research groups have attempted using computational studies including docking analyses. Since there are too many 3D structures for BACE1 in the protein database, the selection of suitable crystal structures is a key prerequisite for the successful application of molecular docking. We employed a multi-structure docking protocol. In which 615 ligands' structures were docked into 150 BACE1 structures. The large number of the resultant docking scores were post-processed by different data analysis methods including exploratory data analysis, regression analysis and discriminant analysis. It was found that using one crystal structure for docking did not result in high accuracy for predicting activity of the BACE1 inhibitors. Instead, using of the multi-structural docking scores, post-processed by chemometrics methods arrived to highly accurate predictive models. In this regards, the PDB accession codes of 4B70, 4DVF and 2WEZ could discriminate between active and inactive compounds, with higher accuracy. Clustering of the BACE1 structures based on principal component analysis of the crystallographic structures the revealed that the discriminant structures are in the center of the clusters. Thus, these structures can be selected as predominant crystal structures for docking studies of non-peptidic BACE1 inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

Specific ability of sulfur-ligands on removal of 203Hg-labeled organomercury from hemoglobin in comparison with nitrogen-ligands

International Nuclear Information System (INIS)

Hojo, Yasuji; Sugiura, Yukio; Tanaka, Hisashi

1975-01-01

Removal of 203 Hg-labeled organomercurials, bound to sulfhydryl groups of hemoglobin, by various chelating agents was investigated by the use of equilibrium dialysis. Organomercurials employed were chlormerodrin, methylmercury, ethylmercury and phenylmercury compounds. Higher and more specific effects of the sulfur-ligands, such as penicillamine and glutathione, on removal of organomercurial were found as compared with those of the nitrogen-ligands such as EDTA, glycine and polymethylenediamines. Linear correlation was observed between the degree of organomercury elimination from hemoglobin and the stability constant (log K 1 ) of 1:1 organomercury complex in both the sulfur- and nitrogen-ligand systems and at the same value of log K 1 , the elimination-effect of sulfur-ligands was extremely greater than that of the nitrogen-ligands. The relationship between the average percentage of removal and the Taft's polar substituent constant of organic moiety of the metal was also linear among the organomercury compounds other than chlormerodrin. The average removal percentage by sulfur-ligands increased in the order, ethylmercury>methylmercury>phenylmercury, while that of the nitrogen-ligands was not different among the organomercurials investigated. In addition, direct ligand-exchange reaction between hemoglobin-SH and the ligand coordinating-atom (S or N) against organomercurials rather than Ssub(N2) reaction via the ternary complex, hemoglobin-S-RHg-ligand, is postulated. (auth.)

Synthesis, Spectroscopy, Thermal Analysis, Magnetic Properties and Biological Activity Studies of Cu(II and Co(II Complexes with Schiff Base Dye Ligands

Directory of Open Access Journals (Sweden)

Saeid Amani

2012-05-01

Full Text Available Three azo group-containing Schiff base ligands, namely 1-{3-[(3-hydroxy-propyliminomethyl]-4-hydroxyphenylazo}-4-nitrobenzene (2a, 1-{3-[(3-hydroxypropyl-iminomethyl]-4-hydroxyphenylazo}-2-chloro-4-nitrobenzene (2b and 1-{3-[(3-hydroxy-propyliminomethyl]-4-hydroxyphenylazo}-4-chloro-3-nitrobenzene (2c were prepared. The ligands were characterized by elemental analysis, FTIR spectroscopy, UV-Vis spectroscopy, ¹³C- and ¹H-NMR spectroscopy and thermogravimetric analysis. Next the corresponding copper(II and cobalt(II metal complexes were synthesized and characterized by the physicochemical and spectroscopic methods of elemental analysis, FTIR spectroscopy, UV-Vis spectroscopy, magnetic moment measurements, and thermogravimetric analysis (TGA and (DSC. The room temperature effective magnetic moments of complexes are 1.45, 1.56, 1.62, 2.16, 2.26 and 2.80 B.M. for complexes 3a, 3b, 3c, 4a 4b, and 4c, respectively, indicating that the complexes are paramagnetic with considerable electronic communication between the two metal centers.

Inspired gas humidity and temperature during mechanical ventilation with the Stephanie ventilator.

Science.gov (United States)

Preo, Bianca L; Shadbolt, Bruce; Todd, David A

2013-11-01

To measure inspired gas humidity and temperature delivered by a Stephanie neonatal ventilator with variations in (i) circuit length; (ii) circuit insulation; (iii) proximal airway temperature probe (pATP) position; (iv) inspiratory temperature (offset); and (v) incubator temperatures. Using the Stephanie neonatal ventilator, inspired gas humidity and temperature were measured during mechanical ventilation at the distal inspiratory limb and 3 cm down the endotracheal tube. Measurements were made with a long or short circuit; with or without insulation of the inspiratory limb; proximal ATP (pATP) either within or external to the incubator; at two different inspiratory temperature (offset) of 37(-0.5) and 39(-2.0)°C; and at three different incubator temperatures of 32, 34.5, and 37°C. Long circuits produced significantly higher inspired humidity than short circuits at all incubator settings, while only at 32°C was the inspired temperature higher. In the long circuits, insulation further improved the inspired humidity especially at 39(-2.0)°C, while only at incubator temperatures of 32 and 37°C did insulation significantly improve inspired temperature. Positioning the pATP outside the incubator did not result in higher inspired humidity but did significantly improve inspired temperature. An inspiratory temperature (offset) of 39(-2.0)°C delivered significantly higher inspired humidity and temperature than the 37(-0.5)°C especially when insulated. Long insulated Stephanie circuits should be used for neonatal ventilation when the infant is nursed in an incubator. The recommended inspiratory temperature (offset) of 37(-0.5)°C produced inspired humidity and temperature below international standards, and we suggest an increase to 39(-2.0)°C. © 2013 John Wiley & Sons Ltd.

FieldChopper, a new tool for automatic model generation and virtual screening based on molecular fields.

Science.gov (United States)

Kalliokoski, Tuomo; Ronkko, Toni; Poso, Antti

2008-06-01

Algorithms were developed for ligand-based virtual screening of molecular databases. FieldChopper (FC) is based on the discretization of the electrostatic and van der Waals field into three classes. A model is built from a set of superimposed active molecules. The similarity of the compounds in the database to the model is then calculated using matrices that define scores for comparing field values of different categories. The method was validated using 12 publicly available data sets by comparing the method to the electrostatic similarity comparison program EON. The results suggest that FC is competitive with more complex descriptors and could be used as a molecular sieve in virtual screening experiments when multiple active ligands are known.

Ligand cluster-based protein network and ePlatton, a multi-target ligand finder.

Science.gov (United States)

Du, Yu; Shi, Tieliu

2016-01-01

Small molecules are information carriers that make cells aware of external changes and couple internal metabolic and signalling pathway systems with each other. In some specific physiological status, natural or artificial molecules are used to interact with selective biological targets to activate or inhibit their functions to achieve expected biological and physiological output. Millions of years of evolution have optimized biological processes and pathways and now the endocrine and immune system cannot work properly without some key small molecules. In the past thousands of years, the human race has managed to find many medicines against diseases by trail-and-error experience. In the recent decades, with the deepening understanding of life and the progress of molecular biology, researchers spare no effort to design molecules targeting one or two key enzymes and receptors related to corresponding diseases. But recent studies in pharmacogenomics have shown that polypharmacology may be necessary for the effects of drugs, which challenge the paradigm, 'one drug, one target, one disease'. Nowadays, cheminformatics and structural biology can help us reasonably take advantage of the polypharmacology to design next-generation promiscuous drugs and drug combination therapies. 234,591 protein-ligand interactions were extracted from ChEMBL. By the 2D structure similarity, 13,769 ligand emerged from 156,151 distinct ligands which were recognized by 1477 proteins. Ligand cluster- and sequence-based protein networks (LCBN, SBN) were constructed, compared and analysed. For assisting compound designing, exploring polypharmacology and finding possible drug combination, we integrated the pathway, disease, drug adverse reaction and the relationship of targets and ligand clusters into the web platform, ePlatton, which is available at http://www.megabionet.org/eplatton. Although there were some disagreements between the LCBN and SBN, communities in both networks were largely the same

Transferable Force Field for Metal–Organic Frameworks from First-Principles: BTW-FF

Science.gov (United States)

2014-01-01

We present an ab-initio derived force field to describe the structural and mechanical properties of metal–organic frameworks (or coordination polymers). The aim is a transferable interatomic potential that can be applied to MOFs regardless of metal or ligand identity. The initial parametrization set includes MOF-5, IRMOF-10, IRMOF-14, UiO-66, UiO-67, and HKUST-1. The force field describes the periodic crystal and considers effective atomic charges based on topological analysis of the Bloch states of the extended materials. Transferable potentials were developed for the four organic ligands comprising the test set and for the associated Cu, Zn, and Zr metal nodes. The predicted materials properties, including bulk moduli and vibrational frequencies, are in agreement with explicit density functional theory calculations. The modal heat capacity and lattice thermal expansion are also predicted. PMID:25574157

Immobilisation of ligands by radio-derivatized polymers; Immobilisering av ligander med radioderiverte polymerer

Energy Technology Data Exchange (ETDEWEB)

Varga, J.M.; Fritsch, P.

1995-01-30

The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs.

Biomimetics inspired surfaces for drag reduction and oleophobicity/philicity

Directory of Open Access Journals (Sweden)

Bharat Bhushan

2011-02-01

Full Text Available The emerging field of biomimetics allows one to mimic biology or nature to develop nanomaterials, nanodevices, and processes which provide desirable properties. Hierarchical structures with dimensions of features ranging from the macroscale to the nanoscale are extremely common in nature and possess properties of interest. There are a large number of objects including bacteria, plants, land and aquatic animals, and seashells with properties of commercial interest. Certain plant leaves, such as lotus (Nelumbo nucifera leaves, are known to be superhydrophobic and self-cleaning due to the hierarchical surface roughness and presence of a wax layer. In addition to a self-cleaning effect, these surfaces with a high contact angle and low contact angle hysteresis also exhibit low adhesion and drag reduction for fluid flow. An aquatic animal, such as a shark, is another model from nature for the reduction of drag in fluid flow. The artificial surfaces inspired from the shark skin and lotus leaf have been created, and in this article the influence of structure on drag reduction efficiency is reviewed. Biomimetic-inspired oleophobic surfaces can be used to prevent contamination of the underwater parts of ships by biological and organic contaminants, including oil. The article also reviews the wetting behavior of oil droplets on various superoleophobic surfaces created in the lab.

Thermodynamic Characterization of Hydration Sites from Integral Equation-Derived Free Energy Densities: Application to Protein Binding Sites and Ligand Series.

Science.gov (United States)

Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Lionta, Evanthia; Heil, Jochen; Kast, Stefan M

2017-07-24

Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design. Unlike molecular dynamics-based approaches, 3D RISM theory allows for fast and noise-free calculations using the same detailed level of solute-solvent interaction description. Here we correlate molecular water entities instead of mere site density maxima with local contributions to the solvation free energy using novel algorithms. Distinct water molecules and hydration sites are investigated in multiple protein-ligand X-ray structures, namely streptavidin, factor Xa, and factor VIIa, based on 3D RISM-derived free energy density fields. Our approach allows the semiquantitative assessment of whether a given structural water molecule can potentially be targeted for replacement in structure-based design. Finally, PLS-based regression models from free energy density fields used within a 3D-QSAR approach (CARMa - comparative analysis of 3D RISM Maps) are shown to be able to extract relevant information for the interpretation of structure-activity relationship (SAR) trends, as demonstrated for a series of serine protease inhibitors.

Multiple pathways of sigma(1) receptor ligand uptakes into primary cultured neuronal cells.

Science.gov (United States)

Yamamoto, H; Karasawa, J; Sagi, N; Takahashi, S; Horikomi, K; Okuyama, S; Nukada, T; Sora, I; Yamamoto, T

2001-08-03

Although many antipsychotics have affinities for sigma receptors, the transportation pathway of exogenous sigma(1) receptor ligands to intracellular type-1 sigma receptors are not fully understood. In this study, sigma(1) receptor ligand uptakes were studied using primary cultured neuronal cells. [(3)H](+)-pentazocine and [(3)H](R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377), used as a selective sigma(1) receptor ligands, were taken up in a time-, energy- and temperature-dependent manner, suggesting that active transport mechanisms were involved in their uptakes. sigma(1) receptor ligands taken up into primary cultured neuronal cells were not restricted to agonists, but also concerned antagonists. The uptakes of these ligands were mainly Na(+)-independent. Kinetic analysis of [(3)H](+)-pentazocine and [(3)H]MS-377 uptake showed K(m) values (microM) of 0.27 and 0.32, and V(max) values (pmol/mg protein/min) of 17.4 and 9.4, respectively. Although both ligands were incorporated, the pharmacological properties of these two ligands were different. Uptake of [(3)H](+)-pentazocine was inhibited in the range 0.4-7.1 microM by all the sigma(1) receptor ligands used, including N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a selective sigma(1) receptor ligand. In contrast, the inhibition of [(3)H]MS-377 uptake was potently inhibited by haloperidol, characterized by supersensitivity (IC(50), approximately 2 nM) and was inhibited by NE-100 with low sensitivity (IC(50), 4.5 microM). Moreover, kinetic analysis revealed that NE-100 inhibited [(3)H]MS-377 uptake in a noncompetitive manner, suggesting that NE-100 acted at a site different from the uptake sites of [(3)H]MS-377. These findings suggest that there are at least two uptake pathways for sigma(1) receptor ligands in primary cultured neuronal cells (i.e. a haloperidol-sensitive pathway and another, unclear, pathway). In

Bio-inspired passive actuator simulating an abalone shell mechanism for structural control

International Nuclear Information System (INIS)

Yang, Henry T Y; Lin, Chun-Hung; Bridges, Daniel; Randall, Connor J; Hansma, Paul K

2010-01-01

An energy dispersion mechanism called 'sacrificial bonds and hidden length', which is found in some biological systems, such as abalone shells and bones, is the inspiration for new strategies for structural control. Sacrificial bonds and hidden length can substantially increase the stiffness and enhance energy dissipation in the constituent molecules of abalone shells and bone. Having been inspired by the usefulness and effectiveness of such a mechanism, which has evolved over millions of years and countless cycles of evolutions, the authors employ the conceptual underpinnings of this mechanism to develop a bio-inspired passive actuator. This paper presents a fundamental method for optimally designing such bio-inspired passive actuators for structural control. To optimize the bio-inspired passive actuator, a simple method utilizing the force–displacement–velocity (FDV) plots based on LQR control is proposed. A linear regression approach is adopted in this research to find the initial values of the desired parameters for the bio-inspired passive actuator. The illustrative examples, conducted by numerical simulation with experimental validation, suggest that the bio-inspired passive actuator based on sacrificial bonds and hidden length may be comparable in performance to state-of-the-art semi-active actuators

Bio-inspired passive actuator simulating an abalone shell mechanism for structural control

Science.gov (United States)

Yang, Henry T. Y.; Lin, Chun-Hung; Bridges, Daniel; Randall, Connor J.; Hansma, Paul K.

2010-10-01

An energy dispersion mechanism called 'sacrificial bonds and hidden length', which is found in some biological systems, such as abalone shells and bones, is the inspiration for new strategies for structural control. Sacrificial bonds and hidden length can substantially increase the stiffness and enhance energy dissipation in the constituent molecules of abalone shells and bone. Having been inspired by the usefulness and effectiveness of such a mechanism, which has evolved over millions of years and countless cycles of evolutions, the authors employ the conceptual underpinnings of this mechanism to develop a bio-inspired passive actuator. This paper presents a fundamental method for optimally designing such bio-inspired passive actuators for structural control. To optimize the bio-inspired passive actuator, a simple method utilizing the force-displacement-velocity (FDV) plots based on LQR control is proposed. A linear regression approach is adopted in this research to find the initial values of the desired parameters for the bio-inspired passive actuator. The illustrative examples, conducted by numerical simulation with experimental validation, suggest that the bio-inspired passive actuator based on sacrificial bonds and hidden length may be comparable in performance to state-of-the-art semi-active actuators.

LISA observations of supermassive black holes: Parameter estimation using full post-Newtonian inspiral waveforms

International Nuclear Information System (INIS)

Trias, Miquel; Sintes, Alicia M.

2008-01-01

We study parameter estimation of supermassive black hole binary systems in the final stage of inspiral using the full post-Newtonian gravitational waveforms. We restrict our analysis to systems in circular orbit with negligible spins, in the mass range 10 8 M · -10 5 M · , and compare the results with those arising from the commonly used restricted post-Newtonian approximation. The conclusions of this work are particularly important with regard to the astrophysical reach of future Laser Interferometer Space Antenna measurements. Our analysis clearly shows that modeling the inspiral with the full post-Newtonian waveform, not only extends the reach to higher mass systems, but also improves in general the parameter estimation. In particular, there are remarkable improvements in angular resolution and distance measurement for systems with a total mass higher than 5x10 6 M · , as well as a large improvement in the mass determination

Reactivity of halide and pseudohalide ligands

International Nuclear Information System (INIS)

Kukushkin, Yu.N.

1987-01-01

Reactivity of halide and pseudohalide (cyanide, azide, thiocyanate, cyanate) ligands tending to form bridge bonds in transition metal (Re, Mo, W) complexes is considered. Complexes where transition metal salts are ligands of other, complex-forming ion, are described. Transformation of innerspheric pseudohalide ligands is an important way of directed synthesis of these metal coordination compounds

Performance of machine learning methods for ligand-based virtual screening.

Science.gov (United States)

Plewczynski, Dariusz; Spieser, Stéphane A H; Koch, Uwe

2009-05-01

Computational screening of compound databases has become increasingly popular in pharmaceutical research. This review focuses on the evaluation of ligand-based virtual screening using active compounds as templates in the context of drug discovery. Ligand-based screening techniques are based on comparative molecular similarity analysis of compounds with known and unknown activity. We provide an overview of publications that have evaluated different machine learning methods, such as support vector machines, decision trees, ensemble methods such as boosting, bagging and random forests, clustering methods, neuronal networks, naïve Bayesian, data fusion methods and others.

Ligand-Enhanced Optical Response of Gold Nanomolecules and Its Fragment Projection Analysis: The Case of Au ₃₀ (SR) ₁₈

Energy Technology Data Exchange (ETDEWEB)

Sementa, Luca; Barcaro, Giovanni; Baseggio, Oscar; De Vetta, Martina; Dass, Amala; Apra, Edoardo; Stener, Mauro; Fortunelli, Alessandro

2017-01-10

Here we investigate via first-principles simulations the optical absorption spectra of three different Au30(SR)18 monolayer-protected clusters (MPC): Au30(StBu)18, which is known in the literature and whose crystal structure is available, and two species – Au30(SPh)18 and Au30(SPh-pNO2)18 – which have been designed by replacing the tert-butyl organic residues with aromatic ones so as to investigate the effects of ligand replacement on the optical response of Au nanomolecules. In analogy with previously studied but rather different Au23(SR)16- anionic species, a substantial ligand-enhancement of the absorption intensity in the optical region is obtained for the Au30(SPhpNO2)18 neutral MPC. This demonstrates that using conjugated aromatic ligands with properly chosen electron withdrawal substituents and exhibiting steric hindrance so as to also achieve charge decompression at the surface is a general approach to enhance MPC photo-absorption intensity in the optical region. Moreover, the ligand-enhancement phenomenon is subjected to a detailed analysis based on fragment projection of electronic excited states and on induced transition densities, leading to a better understanding of its physical origin, thus opening avenues to its more precise control and exploitation.

When science inspires art

CERN Multimedia

Anaïs Vernède

2011-01-01

On Tuesday 18 January 2011, artist Pipilotti Rist came to CERN to find out how science could provide her with a source of inspiration for her art and perhaps to get ideas for future work. Pipilotti, who is an eclectic artist always on the lookout for an original source of inspiration, is almost as passionate about physics as she is about art.   Ever Is Over All, 1997, audio video installation by Pipilotti Rist.  View of the installation at the National Museum for Foreign Art, Sofia, Bulgaria. © Pipilotti Rist. Courtesy the artist and Hauser & Wirth. Photo by Angel Tzvetanov. Swiss video-maker Pipilotti Rist (her real name is Elisabeth Charlotte Rist), who is well-known in the international art world for her highly colourful videos and creations, visited CERN for the first time on Tuesday 18 January 2011.  Her visit represented a trip down memory lane, since she originally studied physics before becoming interested in pursuing a career as an artist and going on to de...

Metal-ligand cooperative activation of nitriles by a ruthenium complex with a de-aromatized PNN pincer ligand

NARCIS (Netherlands)

Eijsink, Linda E; Perdriau, Sébastien C P; de Vries, Johannes G; Otten, Edwin

2016-01-01

The pincer complex (PNN)RuH(CO), with a de-aromatized pyridine in the ligand backbone, is shown to react with nitriles in a metal-ligand cooperative manner. This leads to the formation of a series of complexes with new Ru-N(nitrile) and C(ligand)-C(nitrile) bonds. The initial nitrile cycloaddition

Towards ligand docking including explicit interface water molecules.

Directory of Open Access Journals (Sweden)

Gordon Lemmon

Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

Copper removal using bio-inspired polydopamine coated natural zeolites

Energy Technology Data Exchange (ETDEWEB)

Yu, Yang; Shapter, Joseph G. [Flinders Centre for Nanoscale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Sturt Road, Bedford Park, Adelaide 5042, SA (Australia); Popelka-Filcoff, Rachel [School of Chemical and Physical Sciences, Flinders University, Sturt Road, Bedford Park, Adelaide 5042, SA (Australia); Bennett, John W. [Centre for Nuclear Applications, Australian Nuclear Science and Technology Organisation, Lucas Heights 2234, NSW (Australia); Ellis, Amanda V., E-mail: Amanda.Ellis@flinders.edu.au [Flinders Centre for Nanoscale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Sturt Road, Bedford Park, Adelaide 5042, SA (Australia)

2014-05-01

Highlights: • Natural zeolites were modified with bio-inspired polydopamine. • A 91.4% increase in Cu(II) ion adsorption capacity was observed. • Atomic absorption and neutron activation analysis gave corroborative results. • Neutron activation analysis was used to provide accurate information on 30+ elements. • Approximately 90% of the adsorbed copper could be recovered by 0.1 M HCl treatment. - Abstract: Herein, for the first time, natural clinoptilolite-rich zeolite powders modified with a bio-inspired adhesive, polydopamine (PDA), have been systematically studied as an adsorbent for copper cations (Cu(II)) from aqueous solution. Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA) revealed successful grafting of PDA onto the zeolite surface. The effects of pH (2–5.5), PDA treatment time (3–24 h), contact time (0 to 24 h) and initial Cu(II) ion concentrations (1 to 500 mg dm{sup −3}) on the adsorption of Cu(II) ions were studied using atomic absorption spectroscopy (AAS) and neutron activation analysis (NAA). The adsorption behavior was fitted to a Langmuir isotherm and shown to follow a pseudo-second-order reaction model. The maximum adsorption capacities of Cu(II) were shown to be 14.93 mg g{sup −1} for pristine natural zeolite and 28.58 mg g{sup −1} for PDA treated zeolite powders. This impressive 91.4% increase in Cu(II) ion adsorption capacity is attributed to the chelating ability of the PDA on the zeolite surface. Furthermore studies of recyclability using NAA showed that over 50% of the adsorbed copper could be removed in mild concentrations (0.01 M or 0.1 M) of either acid or base.

Copper removal using bio-inspired polydopamine coated natural zeolites

International Nuclear Information System (INIS)

Yu, Yang; Shapter, Joseph G.; Popelka-Filcoff, Rachel; Bennett, John W.; Ellis, Amanda V.

2014-01-01

Highlights: • Natural zeolites were modified with bio-inspired polydopamine. • A 91.4% increase in Cu(II) ion adsorption capacity was observed. • Atomic absorption and neutron activation analysis gave corroborative results. • Neutron activation analysis was used to provide accurate information on 30+ elements. • Approximately 90% of the adsorbed copper could be recovered by 0.1 M HCl treatment. - Abstract: Herein, for the first time, natural clinoptilolite-rich zeolite powders modified with a bio-inspired adhesive, polydopamine (PDA), have been systematically studied as an adsorbent for copper cations (Cu(II)) from aqueous solution. Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA) revealed successful grafting of PDA onto the zeolite surface. The effects of pH (2–5.5), PDA treatment time (3–24 h), contact time (0 to 24 h) and initial Cu(II) ion concentrations (1 to 500 mg dm −3 ) on the adsorption of Cu(II) ions were studied using atomic absorption spectroscopy (AAS) and neutron activation analysis (NAA). The adsorption behavior was fitted to a Langmuir isotherm and shown to follow a pseudo-second-order reaction model. The maximum adsorption capacities of Cu(II) were shown to be 14.93 mg g −1 for pristine natural zeolite and 28.58 mg g −1 for PDA treated zeolite powders. This impressive 91.4% increase in Cu(II) ion adsorption capacity is attributed to the chelating ability of the PDA on the zeolite surface. Furthermore studies of recyclability using NAA showed that over 50% of the adsorbed copper could be removed in mild concentrations (0.01 M or 0.1 M) of either acid or base

Phantom-like behavior of a DGP-inspired Scalar-Gauss-Bonnet gravity

International Nuclear Information System (INIS)

Nozari, Kourosh; Azizi, Tahereh; Setare, M.R.

2009-01-01

We study the phantom-like behavior of a DGP-inspired braneworld scenario where curvature correction on the brane is taken into account. We include a possible modification of the induced gravity on the brane by incorporating higher order curvature terms of Gauss-Bonnet type. We investigate the cosmological implications of the model and we show that the normal branch of the scenario self-accelerates in this modified scenario without introducing any dark energy component. Also, a phantom-like behavior can be realized in this model without introducing any phantom field that suffers from serious difficulties such as violation of the null energy condition

Caterpillar locomotion-inspired valveless pneumatic micropump using a single teardrop-shaped elastomeric membrane

KAUST Repository

So, Hongyun; Pisano, Albert P.; Seo, Young Ho

2014-01-01

This paper presents a microfluidic pump operated by an asymmetrically deformed membrane, which was inspired by caterpillar locomotion. Almost all mechanical micropumps consist of two major components of fluid halting and fluid pushing parts, whereas the proposed caterpillar locomotion-inspired micropump has only a single, bilaterally symmetric membrane-like teardrop shape. A teardrop-shaped elastomeric membrane was asymmetrically deformed and then consecutively touched down to the bottom of the chamber in response to pneumatic pressure, thus achieving fluid pushing. Consecutive touchdown motions of the teardrop-shaped membrane mimicked the propagation of a caterpillar's hump during its locomotory gait. The initial touchdown motion of the teardrop-shaped membrane at the centroid worked as a valve that blocked the inlet channel, and then, the consecutive touchdown motions pushed fluid in the chamber toward the tail of the chamber connected to the outlet channel. The propagation of the touchdown motion of the teardrop-shaped membrane was investigated using computational analysis as well as experimental studies. This caterpillar locomotion-inspired micropump composed of only a single membrane can provide new opportunities for simple integration of microfluidic systems. © the Partner Organisations 2014.

Caterpillar locomotion-inspired valveless pneumatic micropump using a single teardrop-shaped elastomeric membrane

KAUST Repository

So, Hongyun

2014-01-01

This paper presents a microfluidic pump operated by an asymmetrically deformed membrane, which was inspired by caterpillar locomotion. Almost all mechanical micropumps consist of two major components of fluid halting and fluid pushing parts, whereas the proposed caterpillar locomotion-inspired micropump has only a single, bilaterally symmetric membrane-like teardrop shape. A teardrop-shaped elastomeric membrane was asymmetrically deformed and then consecutively touched down to the bottom of the chamber in response to pneumatic pressure, thus achieving fluid pushing. Consecutive touchdown motions of the teardrop-shaped membrane mimicked the propagation of a caterpillar\\'s hump during its locomotory gait. The initial touchdown motion of the teardrop-shaped membrane at the centroid worked as a valve that blocked the inlet channel, and then, the consecutive touchdown motions pushed fluid in the chamber toward the tail of the chamber connected to the outlet channel. The propagation of the touchdown motion of the teardrop-shaped membrane was investigated using computational analysis as well as experimental studies. This caterpillar locomotion-inspired micropump composed of only a single membrane can provide new opportunities for simple integration of microfluidic systems. © the Partner Organisations 2014.

Biologically inspired coupled antenna beampattern design

Energy Technology Data Exchange (ETDEWEB)

Akcakaya, Murat; Nehorai, Arye, E-mail: makcak2@ese.wustl.ed, E-mail: nehorai@ese.wustl.ed [Department of Electrical and Systems Engineering, Washington University in St Louis, St Louis, MO 63130 (United States)

2010-12-15

We propose to design a small-size transmission-coupled antenna array, and corresponding radiation pattern, having high performance inspired by the female Ormia ochracea's coupled ears. For reproduction purposes, the female Ormia is able to locate male crickets' call accurately despite the small distance between its ears compared with the incoming wavelength. This phenomenon has been explained by the mechanical coupling between the Ormia's ears, which has been modeled by a pair of differential equations. In this paper, we first solve these differential equations governing the Ormia ochracea's ear response, and convert the response to the pre-specified radio frequencies. We then apply the converted response of the biological coupling in the array factor of a uniform linear array composed of finite-length dipole antennas, and also include the undesired electromagnetic coupling due to the proximity of the elements. Moreover, we propose an algorithm to optimally choose the biologically inspired coupling for maximum array performance. In our numerical examples, we compute the radiation intensity of the designed system for binomial and uniform ordinary end-fire arrays, and demonstrate the improvement in the half-power beamwidth, sidelobe suppression and directivity of the radiation pattern due to the biologically inspired coupling.

Origami-inspired, on-demand deployable and collapsible mechanical metamaterials with tunable stiffness

Science.gov (United States)

Zhai, Zirui; Wang, Yong; Jiang, Hanqing

2018-03-01

Origami has been employed to build deployable mechanical metamaterials through folding and unfolding along the crease lines. Deployable metamaterials are usually flexible, particularly along their deploying and collapsing directions, which unfortunately in many cases leads to an unstable deployed state, i.e., small perturbations may collapse the structure along the same deployment path. Here we create an origami-inspired mechanical metamaterial with on-demand deployability and selective collapsibility through energy analysis. This metamaterial has autonomous deployability from the collapsed state and can be selectively collapsed along two different paths, embodying low stiffness for one path and substantially high stiffness for another path. The created mechanical metamaterial yields load-bearing capability in the deployed direction while possessing great deployability and collapsibility. The principle in this work can be utilized to design and create versatile origami-inspired mechanical metamaterials that can find many applications.

PDX toroidal field coils stress analysis

International Nuclear Information System (INIS)

Nikodem, Z.D.; Smith, R.A.

1975-01-01

A method used in the stress analysis of the PDX toroidal field coil is developed. A multilayer coil design of arbitrary dimensions in the shape of either a circle or an oval is considered. The analytical model of the coil and the supporting coil case with connections to the main support structure is analyzed using the finite element technique. The three dimensional magnetic fields and the non-uniform body forces which are a loading condition on a coil due to toroidal and poloidal fields are calculated. The method of analysis permits rapid and economic evaluations of design changes in coil geometry as well as in coil support structures. Some results pertinent to the design evolution and their comparison are discussed. The results of the detailed stress analysis of the final coil design due to toroidal field, poloidal field and temperature loads are presented

Crystallization of bi-functional ligand protein complexes.

Science.gov (United States)

Antoni, Claudia; Vera, Laura; Devel, Laurent; Catalani, Maria Pia; Czarny, Bertrand; Cassar-Lajeunesse, Evelyn; Nuti, Elisa; Rossello, Armando; Dive, Vincent; Stura, Enrico Adriano

2013-06-01

Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects. Copyright © 2013 Elsevier Inc. All rights reserved.

Autocrine signal transmission with extracellular ligand degradation

Science.gov (United States)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-03-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

Cell-specific targeting by heterobivalent ligands.

Science.gov (United States)

Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

2011-07-20

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

Risk of bacterial cross infection associated with inspiration through flow-based spirometers.

Science.gov (United States)

Bracci, Massimo; Strafella, Elisabetta; Croce, Nicola; Staffolani, Sara; Carducci, Annalaura; Verani, Marco; Valentino, Matteo; Santarelli, Lory

2011-02-01

Bacterial contamination of spirometers has been documented in water-sealed devices, mouthpieces, and connection tubes. Little information is available about bacterial contamination of flow-based apparatuses such as turbine-type spirometers and pneumotachographs. Inspiration through contaminated equipment is a potential source of cross infection. To investigate bacteria mobilization (ie, bacteria detachment and aerosolization from the instrument) during routine spirometric testing, 2 types of flow-based spirometers were used. Bacteria mobilization during artificial inspiration through in-line filters or cardboard mouthpieces was evaluated. Nine hundred workers undergoing periodic spirometric testing were enrolled at the occupational physician office in 30 sessions of 30 subjects each. The participants were asked to perform a forced vital capacity test in a turbine-type spirometer and in an unheated pneumotachograph fitted with disposable in-line filters or cardboard mouthpieces. To evaluate bacterial mobilization, an artificial inspiration was performed and bacterial growth determined. The bacterial growth analysis was assessed after the first and the thirtieth spirometric tests of each session without disinfecting the instruments between tests. In addition, instrument bacterial contamination was evaluated. No significant bacterial mobilization and instrument contamination were found in spirometric tests executed with in-line filters. Conversely, a significant bacterial mobilization and instrument contamination were observed in tests performed with cardboard mouthpieces. Differences between the 2 spirometers were not significant. In-line filters may effectively reduce the risk of bacterial cross infection. Inspiration through flow-based spirometers fitted with disposable cardboard mouthpieces is completely safe when combined with spirometer disinfection/sterilization between subjects. Copyright © 2011 Association for Professionals in Infection Control and

VI International Workshop on Nature Inspired Cooperative Strategies for Optimization

CERN Document Server

Otero, Fernando; Masegosa, Antonio

2014-01-01

Biological and other natural processes have always been a source of inspiration for computer science and information technology. Many emerging problem solving techniques integrate advanced evolution and cooperation strategies, encompassing a range of spatio-temporal scales for visionary conceptualization of evolutionary computation. This book is a collection of research works presented in the VI International Workshop on Nature Inspired Cooperative Strategies for Optimization (NICSO) held in Canterbury, UK. Previous editions of NICSO were held in Granada, Spain (2006 & 2010), Acireale, Italy (2007), Tenerife, Spain (2008), and Cluj-Napoca, Romania (2011). NICSO 2013 and this book provides a place where state-of-the-art research, latest ideas and emerging areas of nature inspired cooperative strategies for problem solving are vigorously discussed and exchanged among the scientific community. The breadth and variety of articles in this book report on nature inspired methods and applications such as Swarm In...

New heteroleptic Zn(II) complexes of thiosemicarbazone and diimine Co-Ligands: Structural analysis and their biological impacts

Science.gov (United States)

Mathan Kumar, Shanmugaiah; Kesavan, Mookkandi Palsamy; Vinoth Kumar, Gujuluva Gangatharan; Sankarganesh, Murugesan; Chakkaravarthi, Ganesan; Rajagopal, Gurusamy; Rajesh, Jegathalaprathaban

2018-02-01

A thiosemicarbazone ligand HL appended new Zn(II) complexes [Zn(L)(bpy)] (1) and [Zn(L)(phen)] (2) (where, HL = {2-(3-bromo-5-chloro-2-hydroxybenzylidene)-N-phenylhydrazinecarbothioamide}, bpy = 2, 2‧-bipyridine and phen = 1, 10-phenanthroline) have been synthesized and well characterized using conventional spectroscopic techniques viz.,1H NMR, FTIR and UV-Vis spectra. The crystal structures of complexes 1 and 2 have been determined by single crystal X-ray diffraction studies. Both the complex 1 (τ = 0.5) and 2 (τ = 0.37) possesses square based pyramidally distorted trigonal bipyramidal geometry. The ground state electronic structures of complexes 1 and 2 were investigated by DFT/B3LYP theoretical analysis using 6-311G (d,p) and LANL2DZ basis set level. The superior DNA binding ability of complex 2 has been evaluated using absorption and fluorescence spectral titration studies. Antimicrobial evaluation reveals that complex 2 endowed better screening than HL and complex 1 against both bacterial as well as fungal species. Consequently, complex 2 possesses highest antibacterial screening against Staphylococcus aureus (MIC = 3.0 ± 0.23 mM) and antifungal screening against Candida albicans (MIC = 6.0 ± 0.11 mM). Furthermore, the anticancer activity of the ligand HL, complexes 1 and 2 have been examined against the MCF-7 cell line (Human breast cancer cell line) using MTT assay. It is remarkable that complex 2 (12 ± 0.67 μM) show highest anticancer activity than HL (25.0 ± 0.91 μM) and complex 1 (15 ± 0.88 μM) due to the presence of phen ligand moiety.

Role of ligands in permanganate oxidation of organics.

Science.gov (United States)

Jiang, Jin; Pang, Su-Yan; Ma, Jun

2010-06-01

We previously demonstrated that several ligands such as phosphate, pyrophosphate, EDTA, and humic acid could significantly enhance permanganate oxidation of triclosan (one phenolic biocide), which was explained by the contribution of ligand-stabilized reactive manganese intermediates in situ formed upon permanganate reduction. To further understand the underlying mechanism, we comparatively investigated the influence of ligands on permanganate oxidation of bisphenol A (BPA, one phenolic endocrine-disrupting chemical), carbamazepine (CBZ, a pharmaceutical containing the olefinic group), and methyl p-tolyl sulfoxide (TMSO, a typical oxygen-atom acceptor). Selected ligands exerted oxidation enhancement for BPA but had negligible influence for CBZ and TMSO. This was mainly attributed to the effects of identified Mn(III) complexes, which would otherwise disproportionate spontaneously in the absence of ligands. The one-electron oxidant Mn(III) species exhibited no reactivity toward CBZ and TMSO for which the two-electron oxygen donation may be the primary oxidation mechanism but readily oxidized BPA. The latter case was a function of pH, the complexing ligand, and the molar [Mn(III)]:[ligand] ratio, generally consistent with the patterns of ligand-affected permanganate oxidation. Moreover, the combination of the one-electron reduction of Mn(III) (Mn(III) + e(-) -->Mn(II)) and the Mn(VII)/Mn(II) reaction in excess ligands (Mn(VII) + 4Mn(II) ----> (ligands) 5Mn(III)) suggested a catalytic role of the Mn(III)/Mn(II) pair in permanganate oxidation of some phenolics in the presence of ligands.

Complexation of biological ligands with lanthanides(III) for MRI: Structure, thermodynamic and methods; Complexation des cations lanthanides trivalents par des ligands d'origine biologique pour l'IRM: Structure, thermodynamique et methodes

Energy Technology Data Exchange (ETDEWEB)

Bonnet, C

2006-07-15

New cyclic ligands derived from sugars and amino-acids form a scaffold carrying a coordination sphere of oxygen atoms suitable to complex Ln(III) ions. In spite of their rather low molecular weights, the complexes display surprisingly high relaxivity values, especially at high field. The ACX and BCX ligands, which are acidic derivatives of modified and cyclo-dextrins, form mono and bimetallic complexes with Ln(III). The LnACX and LnBCX complexes show affinities towards Ln(III) similar to those of tri-acidic ligands. In the bimetallic Lu2ACX complex, the cations are deeply embedded in the cavity of the ligand, as shown by the X-ray structure. In aqueous solution, the number of water molecules coordinated to the cation in the LnACX complex depends on the nature and concentration of the alkali ions of the supporting electrolyte, as shown by luminescence and relaxometric measurements. There is only one water molecule coordinated in the LnBCX complex, which enables us to highlight an important second sphere contribution to relaxivity. The NMR study of the RAFT peptidic ligand shows the complexation of Ln(III), with an affinity similar to those of natural ligands derived from calmodulin. The relaxometric study also shows an important second sphere contribution to relaxivity. To better understand the intricate molecular factors affecting relaxivity, we developed new relaxometric methods based on probe solutes. These methods allow us to determine the charge of the complex, weak affinity constants, trans-metallation constants, and the electronic relaxation rate. (author)

Inspirations in medical genetics.

Science.gov (United States)

Asadollahi, Reza

2016-02-01

There are abundant instances in the history of genetics and medical genetics to illustrate how curiosity, charisma of mentors, nature, art, the saving of lives and many other matters have inspired great discoveries. These achievements from deciphering genetic concepts to characterizing genetic disorders have been crucial for management of the patients. There remains, however, a long pathway ahead. © The Author(s) 2014.

Espacio literario relevante sobre el problema del vendedor viajero (TSP: contenido, clasificación, métodos y campos de inspiración Relevant literary space on travelling salesman problem (TSP: contents, classification, methods and fields of inspiration

Directory of Open Access Journals (Sweden)

Jorge Ivan Pérez Rave

2013-01-01

Full Text Available Se describe y se analiza un espacio literario relevante sobre el Problema del Vendedor Viajero (TSP en términos de contenido, clases de TSP, métodos y campos de inspiración. Los datos empleados provinieron de los trabajos más citados en Scopus sobre el TSP, tanto a través de la historia como en el período 2006-2010. Se encontró que el TSP prevalece en las investigaciones, con enfoques tanto en el problema original como en sus variantes, entre las cuales se identificaron el TSP Múltiple y el TSP Probabilístico. Entre los principales campos de inspiración para resolver el TSP están la evolución biológica y su base genético-molecular, el comportamiento de hormigas reales, la termodinámica, las estrategias sistemáticas para combinar reglas de decisión y la búsqueda de vecindades. Hoy día se tiende a desarrollar métodos híbridos, especialmente integrando enfoques globales con búsquedas locales, y se identifica la necesidad de introducir nuevos campos de inspiración.This paper describes and analyzes, in terms of content, the types of TSP, methods and fields of inspiration - the most relevant "literary space" on TSP. It is built based on the top most cited on the TSP history and the Top 10 cited from 2006 to 2010. The study of TSP still prevails in Research, focusing on the original problem and its variants: Multiple TSP (m-TSP and Probabilistic TSP (PTSP. Evidence shows that there has been progress in the development of TSP solving methods, highlighted by various inspiration fields: biological evolution, behavior of real ants, thermodynamics, systematic strategies for combining decision rules, and neighborhood search. There is a tendency to develop hybrid methods, in particular by integrating global approaches to local search. There is need to introduce new fields of inspiration.

A quantum inspired model of radar range and range-rate measurements with applications to weak value measurements

Science.gov (United States)

Escalante, George

2017-05-01

Weak Value Measurements (WVMs) with pre- and post-selected quantum mechanical ensembles were proposed by Aharonov, Albert, and Vaidman in 1988 and have found numerous applications in both theoretical and applied physics. In the field of precision metrology, WVM techniques have been demonstrated and proven valuable as a means to shift, amplify, and detect signals and to make precise measurements of small effects in both quantum and classical systems, including: particle spin, the Spin-Hall effect of light, optical beam deflections, frequency shifts, field gradients, and many others. In principal, WVM amplification techniques are also possible in radar and could be a valuable tool for precision measurements. However, relatively limited research has been done in this area. This article presents a quantum-inspired model of radar range and range-rate measurements of arbitrary strength, including standard and pre- and post-selected measurements. The model is used to extend WVM amplification theory to radar, with the receive filter performing the post-selection role. It is shown that the description of range and range-rate measurements based on the quantum-mechanical measurement model and formalism produces the same results as the conventional approach used in radar based on signal processing and filtering of the reflected signal at the radar receiver. Numerical simulation results using simple point scatterrer configurations are presented, applying the quantum-inspired model of radar range and range-rate measurements that occur in the weak measurement regime. Potential applications and benefits of the quantum inspired approach to radar measurements are presented, including improved range and Doppler measurement resolution.

Fifth International Conference on Innovations in Bio-Inspired Computing and Applications

CERN Document Server

Abraham, Ajith; Snášel, Václav

2014-01-01

This volume of Advances in Intelligent Systems and Computing contains accepted papers presented at IBICA2014, the 5th International Conference on Innovations in Bio-inspired Computing and Applications. The aim of IBICA 2014 was to provide a platform for world research leaders and practitioners, to discuss the full spectrum of current theoretical developments, emerging technologies, and innovative applications of Bio-inspired Computing. Bio-inspired Computing remains to be one of the most exciting research areas, and it is continuously demonstrating exceptional strength in solving complex real life problems. The main driving force of the conference was to further explore the intriguing potential of Bio-inspired Computing. IBICA 2014 was held in Ostrava, Czech Republic and hosted by the VSB - Technical University of Ostrava.

Stochastic and infinite dimensional analysis

CERN Document Server

Carpio-Bernido, Maria; Grothaus, Martin; Kuna, Tobias; Oliveira, Maria; Silva, José

2016-01-01

This volume presents a collection of papers covering applications from a wide range of systems with infinitely many degrees of freedom studied using techniques from stochastic and infinite dimensional analysis, e.g. Feynman path integrals, the statistical mechanics of polymer chains, complex networks, and quantum field theory. Systems of infinitely many degrees of freedom create their particular mathematical challenges which have been addressed by different mathematical theories, namely in the theories of stochastic processes, Malliavin calculus, and especially white noise analysis. These proceedings are inspired by a conference held on the occasion of Prof. Ludwig Streit’s 75th birthday and celebrate his pioneering and ongoing work in these fields.

Determination of ligand binding modes in weak protein–ligand complexes using sparse NMR data

Energy Technology Data Exchange (ETDEWEB)

Mohanty, Biswaranjan; Williams, Martin L.; Doak, Bradley C.; Vazirani, Mansha; Ilyichova, Olga [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); Wang, Geqing [La Trobe University, La Trobe Institute for Molecular Bioscience (Australia); Bermel, Wolfgang [Bruker Biospin GmbH (Germany); Simpson, Jamie S.; Chalmers, David K. [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); King, Glenn F. [The University of Queensland, Institute for Molecular Bioscience (Australia); Mobli, Mehdi, E-mail: m.mobli@uq.edu.au [The University of Queensland, Centre for Advanced Imaging (Australia); Scanlon, Martin J., E-mail: martin.scanlon@monash.edu [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia)

2016-11-15

We describe a general approach to determine the binding pose of small molecules in weakly bound protein–ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met {sup ε}CH{sub 3} assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-{sup 13}C,{sup 15}N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein–ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.

Anions mediate ligand binding in Adineta vaga glutamate receptor ion channels.

Science.gov (United States)

Lomash, Suvendu; Chittori, Sagar; Brown, Patrick; Mayer, Mark L

2013-03-05

AvGluR1, a glutamate receptor ion channel from the primitive eukaryote Adineta vaga, is activated by alanine, cysteine, methionine, and phenylalanine, which produce lectin-sensitive desensitizing responses like those to glutamate, aspartate, and serine. AvGluR1 LBD crystal structures reveal an unusual scheme for binding dissimilar ligands that may be utilized by distantly related odorant/chemosensory receptors. Arginine residues in domain 2 coordinate the γ-carboxyl group of glutamate, whereas in the alanine, methionine, and serine complexes a chloride ion acts as a surrogate ligand, replacing the γ-carboxyl group. Removal of Cl(-) lowers affinity for these ligands but not for glutamate or aspartate nor for phenylalanine, which occludes the anion binding site and binds with low affinity. AvGluR1 LBD crystal structures and sedimentation analysis also provide insights into the evolutionary link between prokaryotic and eukaryotic iGluRs and reveal features unique to both classes, emphasizing the need for additional structure-based studies on iGluR-ligand interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ab initio calculation of transport properties between PbSe quantum dots facets with iodide ligands

Science.gov (United States)

Wang, B.; Patterson, R.; Chen, W.; Zhang, Z.; Yang, J.; Huang, S.; Shrestha, S.; Conibeer, G.

2018-01-01

The transport properties between Lead Selenide (PbSe) quantum dots decorated with iodide ligands has been studied using density functional theory (DFT). Quantum conductance at each selected energy levels has been calculated along with total density of states and projected density of states. The DFT calculation is carried on using a grid-based planar augmented wave (GPAW) code incorporated with the linear combination of atomic orbital (LCAO) mode and Perdew Burke Ernzerhof (PBE) exchange-correlation functional. Three iodide ligand attached low index facets including (001), (011), (111) are investigated in this work. P-orbital of iodide ligand majorly contributes to density of state (DOS) at near top valence band resulting a significant quantum conductance, whereas DOS of Pb p-orbital shows minor influence. Various values of quantum conductance observed along different planes are possibly reasoned from a combined effect electrical field over topmost surface and total distance between adjacent facets. Ligands attached to (001) and (011) planes possess similar bond length whereas it is significantly shortened in (111) plane, whereas transport between (011) has an overall low value due to newly formed electric field. On the other hand, (111) plane with a net surface dipole perpendicular to surface layers leading to stronger electron coupling suggests an apparent increase of transport probability. Apart from previously mentioned, the maximum transport energy levels located several eVs (1 2 eVs) from the edge of valence band top.

Radiation induced ligand loss from cobalt complexes

International Nuclear Information System (INIS)

Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

2000-01-01

Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

Surface Ligand Promotion of Carbon Dioxide Reduction through Stabilizing Chemisorbed Reactive Intermediates.

Science.gov (United States)

Wang, Zhijiang; Wu, Lina; Sun, Kun; Chen, Ting; Jiang, Zhaohua; Cheng, Tao; Goddard, William A

2018-05-23

We have explored functionalizing metal catalysts with surface ligands as an approach to facilitate electrochemical carbon dioxide reduction reaction (CO 2 RR). To provide a molecular level understanding of the mechanism by which this enhancement occurs, we combine in situ spectroscopy analysis with an interpretation based on quantum mechanics (QM) calculations. We find that a surface ligand can play a critical role in stabilizing the chemisorbed CO 2 , which facilitates CO 2 activation and leads to a 0.3 V decrease in the overpotential for carbon monoxide (CO) formation. Moreover, the presence of the surface ligand leads to nearly exclusive CO production. At -0.6 V (versus reversible hydrogen electrode, RHE), CO is the only significant product with a faradic efficiency of 93% and a current density of 1.9 mA cm -2 . This improvement corresponds to 53-fold enhancement in turnover frequency compared with the Ag nanoparticles (NPs) without surface ligands.

Regulation mechanisms of the FLT3-ligand after irradiation; Mecanismes de regulation du FLT3-ligand apres irradiation

Energy Technology Data Exchange (ETDEWEB)

Prat-Lepesant, M

2005-06-15

The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

2016-01-01

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.

2016-06-22

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Spectroscopic study of cadmium (II) complexes with heterocyclic dithiocarbamate ligands

International Nuclear Information System (INIS)

Garcia-Fontan, S.; Rodriguez-Seoane, P.; Casas, J.S.; Sordo, J.; Jones, M.M.

1993-01-01

Cadmium(II) dithiocarbamates [Cd(dtc) 2 ] (dtc=4-carboxamidopiperidine-1-carbodithioate, morpholine-1-carbodithioate or 4-(2-hydroxyethyl)piperazine-1-carbodithioate) and [Cd(dtc) 2 ].H 2 O (dtc=4-hydroxypiperidine-1-carbodithioate} have been prepared and characterized by thermal analysis and IR and NMR ( 13 C, 113 Cd) spectrometry. Two of these ligands have previously been shown capable of removing cadmium from its aged in vivo storage sites. The use of solid state 13 C NMR measurements to establish the coordination mode of the dithiocarbomate ligands is also examined and the difficulties which arise are discussed. (orig.)

Identifying Marine Copper-Binding Ligands in Seawater

Science.gov (United States)

Whitby, H.; Hollibaugh, J. T.; Maldonado, M. T.; Ouchi, S.; van den Berg, S. M.

2016-02-01

Complexation reactions are important because they affect the bioavailability of trace metals such as copper and iron. For example, organic complexation can determine whether copper is a limiting or a toxic micronutrient at natural levels. Copper competes with iron for complexing ligands, and when iron is limiting, copper can also substitute for iron in some metabolic pathways. The speciation of copper can be measured using complexing capacity titrations, which provide the concentration of individual ligand classes (L1, L2 etc.) and the complex stabilities (log K). Using methods recently developed in our laboratory, we show that the ligands within these classes can be measured independently of titrations, thus confirming the titration method and simultaneously identifying the ligands within each class. Thiols were identified as the L1 ligand class and humic compounds as the weaker L2 class in samples from coastal Georgia, USA, collected monthly from April to December. Log K values of the ligand complexes were consistent with values expected for thiols and humic substances. Recent results from culture studies and from samples collected along Line P, a coastal - oceanic transect in the HNLC region of the NE subarctic Pacific, will be presented in comparison to the estuarine results. This comparison will help to broaden our perspective on copper complexation and the ligands responsible, furthering our understanding of ligand sources and life cycles.

Substrate coated with receptor and labelled ligand for assays

International Nuclear Information System (INIS)

1980-01-01

Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

Affinity purification using recombinant PXR as a tool to characterize environmental ligands.

Science.gov (United States)

Dagnino, Sonia; Bellet, Virginie; Grimaldi, Marina; Riu, Anne; Aït-Aïssa, Sélim; Cavaillès, Vincent; Fenet, Hélène; Balaguer, Patrick

2014-02-01

Many environmental endocrine disrupting compounds act as ligands for nuclear receptors. The human pregnane X receptor (hPXR), for instance, is activated by a variety of environmental ligands such as steroids, pharmaceutical drugs, pesticides, alkylphenols, polychlorinated biphenyls and polybromo diethylethers. Some of us have previously reported the occurrence of hPXR ligands in environmental samples but failed to identify them. The aim of this study was to test whether a PXR-affinity column, in which recombinant hPXR was immobilized on solid support, could help the purification of these chemicals. Using PXR ligands of different affinity (10 nM < EC50 < 10 μM), we demonstrated that the PXR-affinity preferentially column captured ligands with medium to high affinities (EC50 < 1 μM). Furthermore, by using the PXR-affinity column to analyze an environmental sample containing ERα, AhR, AR, and PXR activities, we show that (i) half of the PXR activity of the sample was due to compounds with medium to high affinity for PXR and (ii) PXR shared ligands with ERα, AR, and AhR. These findings demonstrate that the newly developed PXR-affinity column coupled to reporter cell lines represents a valuable tool for the characterization of the nature of PXR active compounds and should therefore guide and facilitate their further analysis. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Embryonic expression of the transforming growth factor beta ligand and receptor genes in chicken.

Science.gov (United States)

Cooley, James R; Yatskievych, Tatiana A; Antin, Parker B

2014-03-01

Transforming growth factor-beta (TGFβ) signaling regulates a myriad of biological processes during embryogenesis, in the adult, and during the manifestation of disease. TGFβ signaling is propagated through one of three TGFβ ligands interacting with Type I and Type II receptors, and Type III co-receptors. Although TGFβ signaling is regulated partly by the combinatorial expression patterns of TGFβ receptors and ligands, a comprehensive gene expression analysis has not been published. Here we report the embryonic mRNA expression patterns in chicken embryos of the canonical TGFβ ligands (TGFB1, TGFB2, and TGFB3) and receptors (TGFBR1, TGFBR2, TGFBR3), plus the Activin A receptor, type 1 (ACVR1) and co receptor Endoglin (ENG) that also transduce TGFβ signaling. TGFB ligands and receptors show dynamic and frequently overlapping expression patterns in numerous embryonic cell layers and structures. Integrating expression information identifies combinations of ligands and receptors that are involved in specific developmental processes including somitogenesis, cardiogenesis and vasculogenesis. Copyright © 2013 Wiley Periodicals, Inc.

Electronic and optoelectronic materials and devices inspired by nature

Science.gov (United States)

Meredith, P.; Bettinger, C. J.; Irimia-Vladu, M.; Mostert, A. B.; Schwenn, P. E.

2013-03-01

Inorganic semiconductors permeate virtually every sphere of modern human existence. Micro-fabricated memory elements, processors, sensors, circuit elements, lasers, displays, detectors, etc are ubiquitous. However, the dawn of the 21st century has brought with it immense new challenges, and indeed opportunities—some of which require a paradigm shift in the way we think about resource use and disposal, which in turn directly impacts our ongoing relationship with inorganic semiconductors such as silicon and gallium arsenide. Furthermore, advances in fields such as nano-medicine and bioelectronics, and the impending revolution of the ‘ubiquitous sensor network’, all require new functional materials which are bio-compatible, cheap, have minimal embedded manufacturing energy plus extremely low power consumption, and are mechanically robust and flexible for integration with tissues, building structures, fabrics and all manner of hosts. In this short review article we summarize current progress in creating materials with such properties. We focus primarily on organic and bio-organic electronic and optoelectronic systems derived from or inspired by nature, and outline the complex charge transport and photo-physics which control their behaviour. We also introduce the concept of electrical devices based upon ion or proton flow (‘ionics and protonics’) and focus particularly on their role as a signal interface with biological systems. Finally, we highlight recent advances in creating working devices, some of which have bio-inspired architectures, and summarize the current issues, challenges and potential solutions. This is a rich new playground for the modern materials physicist.

Trauma-Inspired Prosocial Leadership Development

Science.gov (United States)

Williams, Jenifer Wolf; Allen, Stuart

2015-01-01

Though trauma survivors sometimes emerge as leaders in prosocial causes related to their previous negative or traumatic experiences, little is known about this transition, and limited guidance is available for survivors who hope to make prosocial contributions. To understand what enables trauma-inspired prosocial leadership development, the…

Inspiration til fremtidens naturfaglige uddannelser

DEFF Research Database (Denmark)

Busch, Henrik; Troelsen, Rie; Horst, Sebastian

uddannelsesniveauer • at den naturfaglige uddannelseskultur styrkes • at lærerkompetencerne styrkes. Rapportens 2. bind - den selvstændige publikation Inspiration til fremtidens naturfaglige uddannelser • En antologi indeholder en række essays om væsentlige problemstillinger for naturfagene. Der er tidligere udsendt...

Quantum probability ranking principle for ligand-based virtual screening

Science.gov (United States)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening.

Science.gov (United States)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Synthesis, characterization and thermal study of some transition metal complexes of an asymmetrical tetradentate Schiff base ligand

Directory of Open Access Journals (Sweden)

ACHUT S. MUNDE

2010-03-01

Full Text Available Complexes of Cu(II, Ni(II, Co(II, Mn(II and Fe(III with an asymmetric tetradentate Schiff base ligand derived from dehydroacetic acid, 4-methyl-o-phenylenediamine and salicylic aldehyde were synthesized and characterized by elemental analysis, conductometry, magnetic susceptibility, UV–Vis, IR, 1H-NMR spectroscopy, X-ray diffraction analysis of powdered samples and thermal analysis, and screened for antimicrobial activity. The IR spectral data suggested that the ligand behaves as a dibasic tetadentate ligand towards the central metal ion with an ONNO donor atoms sequence. From the microanalytical data, the stoichiometry of the complexes 1:1 (metal:ligand was found. The physico-chemical data suggested square planar geometry for the Cu(II and Ni(II complexes and octahedral geometry for the Co(II, Mn(II and Fe(III complexes. The thermal behaviour (TGA/DTA of the complexes was studied and kinetic parameters were determined by Horowitz–Metzger and Coats–Redfern methods. The powder X-ray diffraction data suggested a monoclinic crystal system for the Co(II, Mn(II and Fe(III complexes. The ligand and their metal complexes were screened for antibacterial activity against Staphylococcus aureus and Escherichia coli and fungicidal activity against Aspergillus niger and Trichoderma viride.

Biologically inspired toys using artificial muscles

Science.gov (United States)

Bar-Cohen, Y.

2001-01-01

Recent developments in electroactive polymers, so-called artificial muscles, could one day be used to make bionics possible. Meanwhile, as this technology evolves novel mechanisms are expected to emerge that are biologically inspired.

Development of immobilized ligands for actinide separations

International Nuclear Information System (INIS)

Paine, R.T.

1994-01-01

Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined

EAP artificial muscle actuators for bio-inspired intelligent social robotics (Conference Presentation)

Science.gov (United States)

Hanson, David F.

2017-04-01

Bio-inspired intelligent robots are coming of age in both research and industry, propelling market growth for robots and A.I. However, conventional motors limit bio-inspired robotics. EAP actuators and sensors could improve the simplicity, compliance, physical scaling, and offer bio-inspired advantages in robotic locomotion, grasping and manipulation, and social expressions. For EAP actuators to realize their transformative potential, further innovations are needed: the actuators must be robust, fast, powerful, manufacturable, and affordable. This presentation surveys progress, opportunities, and challenges in the author's latest work in social robots and EAP actuators, and proposes a roadmap for EAP actuators in bio-inspired intelligent robotics.

INSPIRE: a new scientific information system for HEP

CERN Document Server

Ivanov, R; CERN. Geneva. IT Department

2010-01-01

The status of high-energy physics (HEP) information systems has been jointly analyzed by the libraries of CERN, DESY, Fermilab and SLAC. As a result, the four laboratories have started the INSPIRE project – a new platform built by moving the successful SPIRES features and content, curated at DESY, Fermilab and SLAC, into the open-source CDS Invenio digital library software that was developed at CERN. INSPIRE will integrate current acquisition workflows and databases to host the entire body of the HEP literature (about one million records), aiming to become the reference HEP scientific information platform worldwide. It will provide users with fast access to full text journal articles and preprints, but also material such as conference slides and multimedia. INSPIRE will empower scientists with new tools to discover and access the results most relevant to their research, enable novel text- and data-mining applications, and deploy new metrics to assess the impact of articles and authors. In addition, it will ...

INSPIRE: a new scientific information system for HEP

CERN Multimedia

Ivanov, R

2009-01-01

The status of high-energy physics (HEP) information systems has been jointly analyzed by the libraries of CERN, DESY, Fermilab and SLAC. As a result, the four laboratories have started the INSPIRE project – a new platform built by moving the successful SPIRES features and content, curated at DESY, Fermilab and SLAC, into the open-source CDS Invenio digital library software that was developed at CERN. INSPIRE will integrate present acquisition workflows and databases to host the entire body of the HEP literature (about one million records), aiming to become the reference HEP scientific information platform worldwide. It will provide users with fast access to full-text journal articles and preprints, but also material such as conference slides and multimedia. INSPIRE will empower scientists with new tools to discover and access the results most relevant to their research, enable novel text- and data-mining applications, and deploy new metrics to assess the impact of articles and authors. In addition, it will ...

The Effect of Nitrogen Surface Ligands on Propane Metathesis: Design and Characterizations of N-modified SBA15-Supported Schrock-type Tungsten Alkylidyne

KAUST Repository

Eid, Ahmed A.

2014-04-01

Catalysis, which is primarily a molecular phenomenon, is an important field of chemistry because it requires the chemical conversion of molecules into other molecules. It also has an effect on many fields, including, but not limited to, industry, environment and life Science[1]. Surface Organometallic Chemistry is an effective methodology for Catalysis as it imports the concept and mechanism of organometallic chemistry, to surface science and heterogeneous catalysis. So, it bridges the gap between homogenous and heterogeneous catalysis[1]. The aim of the present research work is to study the effect of Nitrogen surface ligands on the activity of Alkane, Propane in particular, metathesis. Our approach is based on the preparation of selectively well-defined group (VI) transition metal complexes supported onto mesoporous materials, SBA15 and bearing amido and/or imido ligands. We choose nitrogen ligands because, according to the literature, they showed in some cases better catalytic properties in homogenous catalysis in comparison with their oxygen counterparts[2]. The first section covers the modification of a highly dehydroxylated SBA15 surface using a controlled ammonia treatment. These will result in the preparation of two kind of Nitrogen surface ligands: -\\tOne with vicinal silylamine/silanol, (≡SiNH2)(≡SiOH), noted [N,O]SBA15 and, -\\tAnother\\tone\\twith\\tvicinal\\tbis-silylamine moieties (≡SiNH2)2, noted [N,N]SBA15[3]. The second section covers the reaction of Schrock type Tungsten Carbyne [W(≡C- tBu)(CH2-tBu)3] with those N-surface ligands and their characterizations by FT-IR, multiple quantum solid state NMR (1H, 13C), elemental analysis and gas phase analysis. The third section covers the generation of the active site, tungsten hydride species. Their performance toward propane metathesis reaction using the dynamic reactor technique PID compared toward previous well-known catalysts supported on silica oxide or mesoporous materials[4]. A fairly good

Material requirements for bio-inspired sensing systems

Science.gov (United States)

Biggins, Peter; Lloyd, Peter; Salmond, David; Kusterbeck, Anne

2008-10-01

The aim of developing bio-inspired sensing systems is to try and emulate the amazing sensitivity and specificity observed in the natural world. These capabilities have evolved, often for specific tasks, which provide the organism with an advantage in its fight to survive and prosper. Capabilities cover a wide range of sensing functions including vision, temperature, hearing, touch, taste and smell. For some functions, the capabilities of natural systems are still greater than that achieved by traditional engineering solutions; a good example being a dog's sense of smell. Furthermore, attempting to emulate aspects of biological optics, processing and guidance may lead to more simple and effective devices. A bio-inspired sensing system is much more than the sensory mechanism. A system will need to collect samples, especially if pathogens or chemicals are of interest. Other functions could include the provision of power, surfaces and receptors, structure, locomotion and control. In fact it is possible to conceive of a complete bio-inspired system concept which is likely to be radically different from more conventional approaches. This concept will be described and individual component technologies considered.

Contribution of the deep-inspiration breath-hold technique in patients treated for a left breast cancer by mono-isocentric conformational irradiation; Apport du blocage inspiratoire profond chez des patientes traitees pour un cancer du sein gauche par irradiation conformationnelle mono-isocentrique

Energy Technology Data Exchange (ETDEWEB)

Zioueche, A.; Mege, A.; Bodez, V.; Rauglaudre, G. de [Institut Sainte-Catherine, Avignon (France)

2011-10-15

The authors report a study which aimed at assessing the benefit of a deep-inspiration-breath-hold on heart sparing in 31 women treated in the left breast or wall and locoregional ganglionary areas by three-dimensional conformational irradiation with field-in-field optimization. All heart and lung parameters (delivered doses) have been significantly improved by a deep-inspiration-breath-hold. Short communication

MCMC exploration of supermassive black hole binary inspirals

International Nuclear Information System (INIS)

Cornish, Neil J; Porter, Edward K

2006-01-01

The Laser Interferometer Space Antenna will be able to detect the inspiral and merger of super massive black hole binaries (SMBHBs) anywhere in the universe. Standard matched filtering techniques can be used to detect and characterize these systems. Markov Chain Monte Carlo (MCMC) methods are ideally suited to this and other LISA data analysis problems as they are able to efficiently handle models with large dimensions. Here we compare the posterior parameter distributions derived by an MCMC algorithm with the distributions predicted by the Fisher information matrix. We find excellent agreement for the extrinsic parameters, while the Fisher matrix slightly overestimates errors in the intrinsic parameters

Testing effective quantum gravity with gravitational waves from extreme mass ratio inspirals

International Nuclear Information System (INIS)

Yunes, N; Sopuerta, C F

2010-01-01

Testing deviation of GR is one of the main goals of the proposed Laser Interferometer Space Antenna. For the first time, we consistently compute the generation of gravitational waves from extreme-mass ratio inspirals (stellar compact objects into supermassive black holes) in a well-motivated alternative theory of gravity, that to date remains weakly constrained by double binary pulsar observations. The theory we concentrate on is Chern-Simons (CS) modified gravity, a 4-D, effective theory that is motivated both from string theory and loop-quantum gravity, and which enhances the Einstein-Hilbert action through the addition of a dynamical scalar field and the parity-violating Pontryagin density. We show that although point particles continue to follow geodesics in the modified theory, the background about which they inspiral is a modification to the Kerr metric, which imprints a CS correction on the gravitational waves emitted. CS modified gravitational waves are sufficiently different from the General Relativistic expectation that they lead to significant dephasing after 3 weeks of evolution, but such dephasing will probably not prevent detection of these signals, but instead lead to a systematic error in the determination of parameters. We end with a study of radiation-reaction in the modified theory and show that, to leading-order, energy-momentum emission is not CS modified, except possibly for the subdominant effect of scalar-field emission. The inclusion of radiation-reaction will allow for tests of CS modified gravity with space-borne detectors that might be two orders of magnitude larger than current binary pulsar bounds.

Entangled zinc-ditetrazolate frameworks involving in situ ligand synthesis and topological modulation by various secondary N-donor ligands

International Nuclear Information System (INIS)

Li Yunwu; Chen Weilin; Wang Yonghui; Li Yangguang; Wang Enbo

2009-01-01

The introduction of various secondary N-donor ligands into an in situ ditetrazolate-ligand synthesis system of terephthalonitrile, NaN 3 and ZnCl 2 led to the formation of three new entangled frameworks Zn(pdtz)(4,4'-bipy).3H 2 O (1), [Zn(pdtz)(bpp)] 2 .3H 2 O (2) and Zn(pdtz) 0.5 (N 3 )(2,2'-bipy) (3) (4,4'-bipy=4,4'-bipyridine; bpp=1,3-bis(4-pyridyl)propane; 2,2'-bipy=2,2'-bipyridine; H 2 pdtz=5,5'-1,4-phenylene-ditetrazole). The formation of pdtz 2- ligand involves the Sharpless [2+3] cycloaddition reaction between terephthalonitrile and NaN 3 in the presence of Zn 2+ ion as a Lewis-acid catalyst under hydrothermal conditions. Compound 1 exhibits a fivefold interpenetrating 3D framework based on the diamondoid topology. Compound 2 displays a twofold parallel interpenetrating framework based on the wavelike individual network. Compound 3 possesses a 2D puckered network. These new Zn-ditetrazolate frameworks are highly dependent on the modulation of different secondary N-donor ligands. Their luminescent properties were investigated. - Graphical abstract: Three new entangled frameworks were prepared by an in situ ditetrazolate-ligand synthesis system assisted with various auxiliary N-donor ligands. The entangled structures can be modulated by different secondary ligands.

Revealing the consequences and errors of substance arising from the inverse confusion between the crystal (ligand) field quantities and the zero-field splitting ones

Energy Technology Data Exchange (ETDEWEB)

Rudowicz, Czesław, E-mail: crudowicz@zut.edu.pl [Institute of Physics, West Pomeranian University of Technology, Al. Piastów 17, 70-310 Szczecin (Poland); Karbowiak, Mirosław [Faculty of Chemistry, University of Wrocław, ul. F. Joliot-Curie 14, 50-383 Wrocław (Poland)

2015-01-01

Survey of recent literature has revealed a doubly-worrying tendency concerning the treatment of the two distinct types of Hamiltonians, namely, the physical crystal field (CF), or equivalently ligand field (LF), Hamiltonians and the zero-field splitting (ZFS) Hamiltonians, which appear in the effective spin Hamiltonians (SH). The nature and properties of the CF (LF) Hamiltonians have been mixed up in various ways with those of the ZFS Hamiltonians. Such cases have been identified in a rapidly growing number of studies of the transition-ion based systems using electron magnetic resonance (EMR), optical spectroscopy, and magnetic measurements. These findings have far ranging implications since these Hamiltonians are cornerstones for interpretation of magnetic and spectroscopic properties of the single transition ions in various crystals or molecules as well as the exchange coupled systems (ECS) of transition ions, e.g. single molecule magnets (SMM) or single ion magnets (SIM). The seriousness of the consequences of such conceptual problems and related terminological confusions has reached a level that goes far beyond simple semantic issues or misleading keyword classifications of papers in journals and scientific databases. The prevailing confusion, denoted as the CF=ZFS confusion, pertains to the cases of labeling the true ZFS quantities as purportedly the CF (LF) quantities. Here we consider the inverse confusion between the CF (LF) quantities and the SH (ZFS) ones, denoted the ZFS=CF confusion, which consists in referring to the parameters (or Hamiltonians), which are the true CF (LF) quantities, as purportedly the ZFS (or SH) quantities. Specific cases of the ZFS=CF confusion identified in recent textbooks, reviews and papers, especially SMM- and SIM-related ones, are surveyed and the pertinent misconceptions are clarified. The serious consequences of the terminological confusions include misinterpretation of data from a wide range of experimental techniques and

Dilution-triggered SMM behavior under zero field in a luminescent Zn2Dy2 tetranuclear complex incorporating carbonato-bridging ligands derived from atmospheric CO2 fixation.

Science.gov (United States)

Titos-Padilla, Silvia; Ruiz, José; Herrera, Juan Manuel; Brechin, Euan K; Wersndorfer, Wolfgang; Lloret, Francesc; Colacio, Enrique

2013-08-19

The synthesis, structure, magnetic, and luminescence properties of the Zn2Dy2 tetranuclear complex of formula {(μ3-CO3)2[Zn(μ-L)Dy(NO3)]2}·4CH3OH (1), where H2L is the compartmental ligand N,N',N″-trimethyl-N,N″-bis(2-hydroxy-3-methoxy-5-methylbenzyl)diethylenetriamine, are reported. The carbonate anions that bridge two Zn(μ-L)Dy units come from the atmospheric CO2 fixation in a basic medium. Fast quantum tunneling relaxation of the magnetization (QTM) is very effective in this compound, so that single-molecule magnet (SMM) behavior is only observed in the presence of an applied dc field of 1000 Oe, which is able to partly suppress the QTM relaxation process. At variance, a 1:10 Dy:Y magnetic diluted sample, namely, 1', exhibits SMM behavior at zero applied direct-current (dc) field with about 3 times higher thermal energy barrier than that in 1 (U(eff) = 68 K), thus demonstrating the important role of intermolecular dipolar interactions in favoring the fast QTM relaxation process. When a dc field of 1000 Oe is applied to 1', the QTM is almost fully suppressed, the reversal of the magnetization slightly slows, and U(eff) increases to 78 K. The dilution results combined with micro-SQUID magnetization measurements clearly indicate that the SMM behavior comes from single-ion relaxation of the Dy(3+) ions. Analysis of the relaxation data points out that a Raman relaxation process could significantly affect the Orbach relaxation process, reducing the thermal energy barrier U(eff) for slow relaxation of the magnetization.

Synthesis, crystal structure and luminescence properties of lanthanide coordination polymers with a new semirigid bridging thenylsalicylamide ligand

International Nuclear Information System (INIS)

Song, Xue-Qin; Wang, Li; Zhao, Meng-Meng; Wang, Xiao-Run; Peng, Yun-Qiao; Cheng, Guo-Quan

2013-01-01

Two new lanthanide coordination polymers based on a semirigid bridging thenylsalicylamide ligand ([Ln 2 L 3 (NO 3 ) 6 ]·(C 4 H 8 O 2 ) 2 ) ∞ were obtained and characterized by elemental analysis, X-ray diffraction, IR and TGA measurements. The two compounds are isostructure and possess one dimensional trapezoid ladder-like chain built up from the connection of isolated LnO 3 (NO 3 ) 3 polyhedra (distorted monocapped antisquare prism) through the ligand. The photoluminescence analysis suggest that there is an efficient ligand-to-Ln(III) energy transfer in Tb(III) complex and the ligand is an efficient “antenna” for Tb(III). From a more general perspective, the results demonstrated herein provide the possibility of controlling the formation of the desired lanthanide coordination structure to enrich the crystal engineering strategy and enlarge the arsenal for developing excellent luminescent lanthanide coordination polymers. - Graphical abstract: We present herein one dimensional lanthanide coordination polymers of a new semirigid exo-bidentate ligand which not only display interesting structures but also possess strong luminescence properties. Display Omitted - Highlights: • We present lanthanide coordination polymers of a new semirigid exo-bidentate ligand. • The lanthanide coordination polymers exhibit interesting structures. • The luminescent properties of Tb(III) complexes are discussed in detail

Synthesis and Crystal Structure of Dinuclear Cadmium(II) Complex with Dipodal Ligand

International Nuclear Information System (INIS)

Kang, Young Jin; Moon, Suk Hee; Byun, Jong Chul; Park, Ki Min

2010-01-01

the preparation and structural characterization of the discrete dinuclear cadmium(II) complex with the formula [Cd(μ 2 -Cl) 2 Cl 2 ]· 2 (H 2 O)·0.5(CH 3 OH)·0.5(CH 3 CN) obtained from the reaction of CdCl 2 ·2.5H 2 O and podal ligand with quinoline end-groups has been reported. In two cadmium ions are triply bridged by two chloride and one donor atoms of ligand L and adopt distorted pentagonal bipyramidal geometries with seven coordinations. It is notable that example of discrete dinuclear complex which one podal ligand accommodates simultaneously two metal ions is very rare. During the last four decades, the chemistry of macrocyclic and non-cyclic polyethers has attracted an increasing attention because of their selective complexation, cation transport and enzyme chemistry. In the field of coordination chemistry, generally, non-cyclic, crown-type polyether affords the low complexation ability because of its conformational freedom while macrocyclic polyethers such as 18-crown-6 show the excellent complexing ability

Selective extraction of trivalent actinides with hard-soft mixed donor ligands: role of intra-ligand synergism

International Nuclear Information System (INIS)

Ghanty, Tapan K.

2016-01-01

In recent years, considerable attention has been given to understand the coordination chemistry of trivalent lanthanide (Ln) and actinide (An) with various ligands because of its close link with the nuclear waste management processes. It is well known that lanthanide-actinide separation is a challenging and difficult task because of very similar chemical properties of these two series of ions, which are associated with similar ionic radii and coordination numbers. Recently, we have introduced a new concept, 'intra-ligand synergism', where hard donor atom, such as, oxygen preferentially binds to trivalent actinides (An(III)) as compared to the valence iso-electronic trivalent lanthanides (Ln(III)) in presence of another soft donor centre. In the present work, the conventional concept of selective complexation of actinides with soft donor ligands (either S or N donor) has been modified through exploiting this concept, and thereby the higher selectivity of 1,10-phenanthroline-2,9-dicarboxylamide (PDAM) based ligands, namely PDAM and its isobutyl and decyl derivatives towards Am(III) ion has been predicted theoretically through density functional calculations. Subsequently, several such amide derivatives have been synthesized to optimize the solubility of the ligands in organic phase. Finally, solvent extraction experiments have been carried out to validate the theoretical prediction on the selectivity of oxygen donor ligands towards Am(III) as compared to Eu(III), and a maximum separation factor of about 51 has been achieved experimentally using 2,9-bis(N-decylaminocarbonyl)-1,10-phenanthroline ligand. The separation factor is increased with the decrease in pH, which is very interesting since extraction of the Am 3+ ion is considered to be important under highly acidic conditions from the nuclear waste management point of view. (author)

Combined Docking with Classical Force Field and Quantum Chemical Semiempirical Method PM7

Directory of Open Access Journals (Sweden)

A. V. Sulimov

2017-01-01

Full Text Available Results of the combined use of the classical force field and the recent quantum chemical PM7 method for docking are presented. Initially the gridless docking of a flexible low molecular weight ligand into the rigid target protein is performed with the energy function calculated in the MMFF94 force field with implicit water solvent in the PCM model. Among several hundred thousand local minima, which are found in the docking procedure, about eight thousand lowest energy minima are chosen and then energies of these minima are recalculated with the recent quantum chemical semiempirical PM7 method. This procedure is applied to 16 test complexes with different proteins and ligands. For almost all test complexes such energy recalculation results in the global energy minimum configuration corresponding to the ligand pose near the native ligand position in the crystalized protein-ligand complex. A significant improvement of the ligand positioning accuracy comparing with MMFF94 energy calculations is demonstrated.

Combined Docking with Classical Force Field and Quantum Chemical Semiempirical Method PM7.

Science.gov (United States)

Sulimov, A V; Kutov, D C; Katkova, E V; Sulimov, V B

2017-01-01

Results of the combined use of the classical force field and the recent quantum chemical PM7 method for docking are presented. Initially the gridless docking of a flexible low molecular weight ligand into the rigid target protein is performed with the energy function calculated in the MMFF94 force field with implicit water solvent in the PCM model. Among several hundred thousand local minima, which are found in the docking procedure, about eight thousand lowest energy minima are chosen and then energies of these minima are recalculated with the recent quantum chemical semiempirical PM7 method. This procedure is applied to 16 test complexes with different proteins and ligands. For almost all test complexes such energy recalculation results in the global energy minimum configuration corresponding to the ligand pose near the native ligand position in the crystalized protein-ligand complex. A significant improvement of the ligand positioning accuracy comparing with MMFF94 energy calculations is demonstrated.

Autocrine signal transmission with extracellular ligand degradation

International Nuclear Information System (INIS)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-01-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

Dockomatic - automated ligand creation and docking.

Science.gov (United States)

Bullock, Casey W; Jacob, Reed B; McDougal, Owen M; Hampikian, Greg; Andersen, Tim

2010-11-08

The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

Dockomatic - automated ligand creation and docking

Directory of Open Access Journals (Sweden)

Hampikian Greg

2010-11-01

Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

Challenges predicting ligand-receptor interactions of promiscuous proteins: the nuclear receptor PXR.

Directory of Open Access Journals (Sweden)

Sean Ekins

2009-12-01

Full Text Available Transcriptional regulation of some genes involved in xenobiotic detoxification and apoptosis is performed via the human pregnane X receptor (PXR which in turn is activated by structurally diverse agonists including steroid hormones. Activation of PXR has the potential to initiate adverse effects, altering drug pharmacokinetics or perturbing physiological processes. Reliable computational prediction of PXR agonists would be valuable for pharmaceutical and toxicological research. There has been limited success with structure-based modeling approaches to predict human PXR activators. Slightly better success has been achieved with ligand-based modeling methods including quantitative structure-activity relationship (QSAR analysis, pharmacophore modeling and machine learning. In this study, we present a comprehensive analysis focused on prediction of 115 steroids for ligand binding activity towards human PXR. Six crystal structures were used as templates for docking and ligand-based modeling approaches (two-, three-, four- and five-dimensional analyses. The best success at external prediction was achieved with 5D-QSAR. Bayesian models with FCFP_6 descriptors were validated after leaving a large percentage of the dataset out and using an external test set. Docking of ligands to the PXR structure co-crystallized with hyperforin had the best statistics for this method. Sulfated steroids (which are activators were consistently predicted as non-activators while, poorly predicted steroids were docked in a reverse mode compared to 5alpha-androstan-3beta-ol. Modeling of human PXR represents a complex challenge by virtue of the large, flexible ligand-binding cavity. This study emphasizes this aspect, illustrating modest success using the largest quantitative data set to date and multiple modeling approaches.

New development thoughts on the bio-inspired intelligence based control for unmanned combat aerial vehicle

Institute of Scientific and Technical Information of China (English)

无

2010-01-01

Bio-inspired intelligence is in the spotlight in the field of international artificial intelligence,and unmanned combat aerial vehicle(UCAV),owing to its potential to perform dangerous,repetitive tasks in remote and hazardous,is very promising for the technological leadership of the nation and essential for improving the security of society.On the basis of introduction of bioinspired intelligence and UCAV,a series of new development thoughts on UCAV control are proposed,including artificial brain based high-level autonomous control for UCAV,swarm intelligence based cooperative control for multiple UCAVs,hy-brid swarm intelligence and Bayesian network based situation assessment under complicated combating environments, bio-inspired hardware based high-level autonomous control for UCAV,and meta-heuristic intelligence based heterogeneous cooperative control for multiple UCAVs and unmanned combat ground vehicles(UCGVs).The exact realization of the proposed new development thoughts can enhance the effectiveness of combat,while provide a series of novel breakthroughs for the intelligence,integration and advancement of future UCAV systems.

A molecular dynamics investigation of CDK8/CycC and ligand binding: conformational flexibility and implication in drug discovery

Science.gov (United States)

Cholko, Timothy; Chen, Wei; Tang, Zhiye; Chang, Chia-en A.

2018-05-01

Abnormal activity of cyclin-dependent kinase 8 (CDK8) along with its partner protein cyclin C (CycC) is a common feature of many diseases including colorectal cancer. Using molecular dynamics (MD) simulations, this study determined the dynamics of the CDK8-CycC system and we obtained detailed breakdowns of binding energy contributions for four type-I and five type-II CDK8 inhibitors. We revealed system motions and conformational changes that will affect ligand binding, confirmed the essentialness of CycC for inclusion in future computational studies, and provide guidance in development of CDK8 binders. We employed unbiased all-atom MD simulations for 500 ns on twelve CDK8-CycC systems, including apoproteins and protein-ligand complexes, then performed principal component analysis (PCA) and measured the RMSF of key regions to identify protein dynamics. Binding pocket volume analysis identified conformational changes that accompany ligand binding. Next, H-bond analysis, residue-wise interaction calculations, and MM/PBSA were performed to characterize protein-ligand interactions and find the binding energy. We discovered that CycC is vital for maintaining a proper conformation of CDK8 to facilitate ligand binding and that the system exhibits motion that should be carefully considered in future computational work. Surprisingly, we found that motion of the activation loop did not affect ligand binding. Type-I and type-II ligand binding is driven by van der Waals interactions, but electrostatic energy and entropic penalties affect type-II binding as well. Binding of both ligand types affects protein flexibility. Based on this we provide suggestions for development of tighter-binding CDK8 inhibitors and offer insight that can aid future computational studies.

Kids as Airborne Mission Scientists: Designing PBL To Inspire Kids.

Science.gov (United States)

Koszalka, Tiffany A.; Grabowski, Barbara L.; Kim, Younghoon

Problem-based learning (PBL) has great potential for inspiring K-12 learning. KaAMS, a NASA funded project and an example of PBL, was designed to help teachers inspire middle school students to learn science. The students participate as scientists investigating environmental problems using NASA airborne remote sensing data. Two PBL modules were…

INSPIRED High School Computing Academies

Science.gov (United States)

Doerschuk, Peggy; Liu, Jiangjiang; Mann, Judith

2011-01-01

If we are to attract more women and minorities to computing we must engage students at an early age. As part of its mission to increase participation of women and underrepresented minorities in computing, the Increasing Student Participation in Research Development Program (INSPIRED) conducts computing academies for high school students. The…

Inspiration: One Percent and Rising

Science.gov (United States)

Walling, Donovan R.

2009-01-01

Inventor Thomas Edison once famously declared, "Genius is one percent inspiration and ninety-nine percent perspiration." If that's the case, then the students the author witnessed at the International Student Media Festival (ISMF) last November in Orlando, Florida, are geniuses and more. The students in the ISMF pre-conference workshop…

Radioactive contaminants in the subsurface: the influence of complexing ligands on trace metal speciation

International Nuclear Information System (INIS)

Hummel, W. . Author

2006-01-01

Equilibrium thermodynamics is one of the pillars which support safety analyzes of repositories for radioactive waste. The research summarized in this review deals with approaches to resolve the problems related to thermodynamic equilibrium constants and solubility of solid phases in the field of radioactive waste management. The results have been obtained at the Paul Scherrer Institut between 1995 and 2005 and comprise the scientific basis of the author's habilitation thesis in the field of nuclear environmental chemistry. The topics are grouped according to three different levels of problem solving strategies: critical and comprehensive reviews of the available literature, which are necessary in order to establish a reliable chemical thermodynamic database that fulfils the requirements for rigorous modeling of the behavior of the actinides and fission products in the environment. In many case studies involving inorganic and simple organic ligands a serious lack of reliable thermodynamic data is encountered. There, a new modeling approach to estimate the effects of these missing data was applied. This so called 'backdoor approach' begins with the question, 'What total concentration of a ligand is necessary to significantly influence the speciation, and hence the solubility, of a given trace metal?' In the field of natural organics, mainly humic and fulvic acids, we face an ill-defined problem concerning the molecular structure of the ligands. There, a pragmatic approach for performance assessment purposes was applied, the 'conservative roof' approach, which does not aim to accurately model all experimental data, but allows estimates of maximum effects on metal complexation by humic substances to be calculated. (author)

Plant twitter: ligands under 140 amino acids enforcing stomatal patterning.

Science.gov (United States)

Rychel, Amanda L; Peterson, Kylee M; Torii, Keiko U

2010-05-01

Stomata are an essential land plant innovation whose patterning and density are under genetic and environmental control. Recently, several putative ligands have been discovered that influence stomatal density, and they all belong to the epidermal patterning factor-like family of secreted cysteine-rich peptides. Two of these putative ligands, EPF1 and EPF2, are expressed exclusively in the stomatal lineage cells and negatively regulate stomatal density. A third, EPFL6 or CHALLAH, is also a negative regulator of density, but is expressed subepidermally in the hypocotyl. A fourth, EPFL9 or STOMAGEN, is expressed in the mesophyll tissues and is a positive regulator of density. Genetic evidence suggests that these ligands may compete for the same receptor complex. Proper stomatal patterning is likely to be an intricate process involving ligand competition, regional specificity, and communication between tissue layers. EPFL-family genes exist in the moss Physcomitrella patens, the lycophyte Selaginella moellendorffii, and rice, Oryza sativa, and their sequence analysis yields several genes some of which are related to EPF1, EPF2, EPFL6, and EPFL9. Presence of these EPFL family members in the basal land plants suggests an exciting hypothesis that the genetic components for stomatal patterning originated early in land plant evolution.

Crystal structures and Moessbauer spectra of spin-crossover iron(III) complexes of quinquedentate ligands

International Nuclear Information System (INIS)

Maeda, Yonezo; Noda, Yosuke; Oshio, Hiroki; Takashima, Yoshimasa; Matsumoto, Naohide

1994-01-01

Magnetic properties, Moessbauer spectra and crystal structures of spin-crossover iron(III) complexes with a quinquedentate ligand [FeLX]BPh 4 are reported. X and L denote a unidentate ligand and a quinquedentate ligand, respectively. [Fe(mbpN)(im)]BPh 4 shows spin-crossover behavior in an appropriate organic solvent, and [Fe(mbpN)(lut)]BPh 4 , [Fe(bpN)(py)]BPh 4 and [Fe(salten)X]BPh 4 (X = 4me-py or 2me-im) show spin-crossover behavior in a solid and in an organic solvent. It was found that the ligand field strength of salten was stronger than that of mbpN. The rates of spin-state interexchange in the complexes are as fast as the inverse of the lifetime (1 x 10 -7 s) of the Moessbauer nuclear level. The Moessbauer spectroscopic behavior of [Fe(mbpN)(lut)]BPh 4 and [Fe(bpN)(py)]BPh 4 is different to that of [Fe(salten)X]BPh 4 (X = 4me-py or 2me-im). The difference was ascribed to the different geometrical positions of the corresponding anions. (orig.)

Revealing the consequences and errors of substance arising from the inverse confusion between the crystal (ligand) field quantities and the zero-field splitting ones

Science.gov (United States)

Rudowicz, Czesław; Karbowiak, Mirosław

2015-01-01

Survey of recent literature has revealed a doubly-worrying tendency concerning the treatment of the two distinct types of Hamiltonians, namely, the physical crystal field (CF), or equivalently ligand field (LF), Hamiltonians and the zero-field splitting (ZFS) Hamiltonians, which appear in the effective spin Hamiltonians (SH). The nature and properties of the CF (LF) Hamiltonians have been mixed up in various ways with those of the ZFS Hamiltonians. Such cases have been identified in a rapidly growing number of studies of the transition-ion based systems using electron magnetic resonance (EMR), optical spectroscopy, and magnetic measurements. These findings have far ranging implications since these Hamiltonians are cornerstones for interpretation of magnetic and spectroscopic properties of the single transition ions in various crystals or molecules as well as the exchange coupled systems (ECS) of transition ions, e.g. single molecule magnets (SMM) or single ion magnets (SIM). The seriousness of the consequences of such conceptual problems and related terminological confusions has reached a level that goes far beyond simple semantic issues or misleading keyword classifications of papers in journals and scientific databases. The prevailing confusion, denoted as the CF=ZFS confusion, pertains to the cases of labeling the true ZFS quantities as purportedly the CF (LF) quantities. Here we consider the inverse confusion between the CF (LF) quantities and the SH (ZFS) ones, denoted the ZFS=CF confusion, which consists in referring to the parameters (or Hamiltonians), which are the true CF (LF) quantities, as purportedly the ZFS (or SH) quantities. Specific cases of the ZFS=CF confusion identified in recent textbooks, reviews and papers, especially SMM- and SIM-related ones, are surveyed and the pertinent misconceptions are clarified. The serious consequences of the terminological confusions include misinterpretation of data from a wide range of experimental techniques and

Some mixed ligand hydridocarbonyl and hydridophosphine complexes of ruthenium(II) and iridium(III)

International Nuclear Information System (INIS)

Pandey, R.N.; Kumar, Sunil; Kumar, Arun; Kumar, S.K.

1993-01-01

Mixed-ligand hydridocarbonyl and hydridophosphine complexes of Ru II and Ir III have been isolated from the displacement reaction of [RuH(CO)(Pφ 3 ) 3 Cl] with ligand isonicotinic acid hydrazide (INAH) in benzene medium. Most probable structures are assigned on the basis of elemental analysis, electronic, infrared and far-infrared spectral studies. In all cases bonding of INAH occurs through amino nitrogen of hydrazine residue. (author). 15 refs., 1 tab

Conformational changes and allosteric communications in human serum albumin due to ligand binding.

Science.gov (United States)

Ahalawat, Navjeet; Murarka, Rajesh K

2015-01-01

It is well recognized that knowledge of structure alone is not sufficient to understand the fundamental mechanism of biomolecular recognition. Information of dynamics is necessary to describe motions involving relevant conformational states of functional importance. We carried out principal component analysis (PCA) of structural ensemble, derived from 84 crystal structures of human serum albumin (HSA) with different ligands and/or different conditions, to identify the functionally important collective motions, and compared with the motions along the low-frequency modes obtained from normal mode analysis of the elastic network model (ENM) of unliganded HSA. Significant overlap is observed in the collective motions derived from PCA and ENM. PCA and ENM analysis revealed that ligand selects the most favored conformation from accessible equilibrium structures of unliganded HSA. Further, we analyzed dynamic network obtained from molecular dynamics simulations of unliganded HSA and fatty acids- bound HSA. Our results show that fatty acids-bound HSA has more robust community network with several routes to communicate among different parts of the protein. Critical nodes (residues) identified from dynamic network analysis are in good agreement with allosteric residues obtained from sequence-based statistical coupling analysis method. This work underscores the importance of intrinsic structural dynamics of proteins in ligand recognition and can be utilized for the development of novel drugs with optimum activity.

Complexation of biological ligands with lanthanides(III) for MRI: Structure, thermodynamic and methods; Complexation des cations lanthanides trivalents par des ligands d'origine biologique pour l'IRM: Structure, thermodynamique et methodes

Energy Technology Data Exchange (ETDEWEB)

Bonnet, C

2006-07-15

New cyclic ligands derived from sugars and amino-acids form a scaffold carrying a coordination sphere of oxygen atoms suitable to complex Ln(III) ions. In spite of their rather low molecular weights, the complexes display surprisingly high relaxivity values, especially at high field. The ACX and BCX ligands, which are acidic derivatives of modified and cyclo-dextrins, form mono and bimetallic complexes with Ln(III). The LnACX and LnBCX complexes show affinities towards Ln(III) similar to those of tri-acidic ligands. In the bimetallic Lu2ACX complex, the cations are deeply embedded in the cavity of the ligand, as shown by the X-ray structure. In aqueous solution, the number of water molecules coordinated to the cation in the LnACX complex depends on the nature and concentration of the alkali ions of the supporting electrolyte, as shown by luminescence and relaxometric measurements. There is only one water molecule coordinated in the LnBCX complex, which enables us to highlight an important second sphere contribution to relaxivity. The NMR study of the RAFT peptidic ligand shows the complexation of Ln(III), with an affinity similar to those of natural ligands derived from calmodulin. The relaxometric study also shows an important second sphere contribution to relaxivity. To better understand the intricate molecular factors affecting relaxivity, we developed new relaxometric methods based on probe solutes. These methods allow us to determine the charge of the complex, weak affinity constants, trans-metallation constants, and the electronic relaxation rate. (author)

Reggio Emilia Inspired Learning Groups: Relationships, Communication, Cognition, and Play

Science.gov (United States)

Hong, Seong Bock; Shaffer, LaShorage; Han, Jisu

2017-01-01

A key aspect of the Reggio Emilia inspired curriculum is a learning group approach that fosters social and cognitive development. The purpose of this paper is to investigate how a Reggio Emilia inspired learning group approach works for children with and without disabilities. This study gives insight into how to form an appropriate learning group…

Fiction and Religion : How Narratives About the Supernatural Inspire Religious Belief

NARCIS (Netherlands)

Davidsen, M.A.

2016-01-01

Thematic issue on 'Fiction and Religion: How Narratives About the Supernatural Inspire Religious Belief', volume 46(4) of Religion. The thematic issue inclues the following articles: Davidsen, Markus Altena, "Fiction and Religion: How Narratives About the Supernatural Inspire Religious Belief –

Screening the efficient biological prospects of triazole allied mixed ligand metal complexes

Science.gov (United States)

Utthra, Ponnukalai Ponya; Kumaravel, Ganesan; Raman, Natarajan

2017-12-01

Triazole appended mixed ligand complexes (1-8) of the general formula [ML (bpy/phen)2]Cl2, where M = Cu(II), Co(II), Ni(II) and Zn(II), L = triazole appended Schiff base (E)sbnd N-(4-nitrobenzylidene)-1H-1,2,4-triazol-3-amine and bpy/phen = 2,2‧-bipyridine/1,10-phenanthroline, have been synthesized. The design and synthesis of this elaborate ligand has been performed with the aim of increasing stability and conjugation of 1,2,4 triazole, whose Schiff base derivatives are known as biologically active compounds thereby exploring their DNA binding affinity and other biological applications. The compounds have been comprehensively characterized by elemental analysis, spectroscopic methods (IR, UV-Vis, EPR, 1H and 13C NMR spectroscopy), ESI mass spectrometry and magnetic susceptibility measurements. The complexes were found to exhibit octahedral geometry. The complexes 1-8 were subjected to DNA binding techniques evaluated using UV-Vis absorption, CV, CD, Fluorescence spectroscopy and hydrodynamic measurements. Complex 5 showed a Kb value of 3.9 × 105 M-1. The DNA damaging efficacy for the complexes was observed to be high compared to the ligand. The antimicrobial screening of the compounds against bacterial and fungal strains indicates that the complexes possess excellent antimicrobial activity than the ligand. The overall biological activity of the complexes with phen as a co-ligand possessed superior potential than the ligand.

Charged black holes in string-inspired gravity II. Mass inflation and dependence on parameters and potentials

Energy Technology Data Exchange (ETDEWEB)

Hansen, Jakob [KISTI,Daejeon 305-806 (Korea, Republic of); Yeom, Dong-han [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University,Taipei 10617, Taiwan (China)

2015-09-07

We investigate the relation between the existence of mass inflation and model parameters of string-inspired gravity models. In order to cover various models, we investigate a Brans-Dicke theory that is coupled to a U(1) gauge field. By tuning a model parameter that decides the coupling between the Brans-Dicke field and the electromagnetic field, we can make both of models such that the Brans-Dicke field is biased toward strong or weak coupling directions after gravitational collapses. We observe that as long as the Brans-Dicke field is biased toward any (strong or weak) directions, there is no Cauchy horizon and no mass inflation. Therefore, we conclude that to induce a Cauchy horizon and mass inflation inside a charged black hole, either there is no bias of the Brans-Dicke field as well as no Brans-Dicke hair outside the horizon or such a biased Brans-Dicke field should be well trapped and controlled by a potential.

Distinct roles of beta1 metal ion-dependent adhesion site (MIDAS), adjacent to MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding sites in ligand recognition by integrin alpha2beta1.

Science.gov (United States)

Valdramidou, Dimitra; Humphries, Martin J; Mould, A Paul

2008-11-21

Integrin-ligand interactions are regulated in a complex manner by divalent cations, and previous studies have identified ligand-competent, stimulatory, and inhibitory cation-binding sites. In collagen-binding integrins, such as alpha2beta1, ligand recognition takes place exclusively at the alpha subunit I domain. However, activation of the alphaI domain depends on its interaction with a structurally similar domain in the beta subunit known as the I-like or betaI domain. The top face of the betaI domain contains three cation-binding sites: the metal-ion dependent adhesion site (MIDAS), the ADMIDAS (adjacent to MIDAS), and LIMBS (ligand-associated metal-binding site). The role of these sites in controlling ligand binding to the alphaI domain has yet to be elucidated. Mutation of the MIDAS or LIMBS completely blocked collagen binding to alpha2beta1; in contrast mutation of the ADMIDAS reduced ligand recognition but this effect could be overcome by the activating monoclonal antibody TS2/16. Hence, the MIDAS and LIMBS appear to be essential for the interaction between alphaI and betaI, whereas occupancy of the ADMIDAS has an allosteric effect on the conformation of betaI. An activating mutation in the alpha2 I domain partially restored ligand binding to the MIDAS and LIMBS mutants. Analysis of the effects of Ca(2+), Mg(2+), and Mn(2+) on ligand binding to these mutants showed that the MIDAS is a ligand-competent site through which Mn(2+) stimulates ligand binding, whereas the LIMBS is a stimulatory Ca(2+)-binding site, occupancy of which increases the affinity of Mg(2+) for the MIDAS.

Synthesis of novel '4+1' Tc(III)/Re(III) mixed-ligand complexes with dendritically modified ligands

International Nuclear Information System (INIS)

Gniazdowska, E.; Kuenstler, J.U.; Stephan, H.; Pietzsch, H.J.

2006-01-01

Coordination chemistry of technetium and rhenium attracts a considerable interest due to the nuclear medicine applications of their radionuclides. Inert, so-called '3+1' or '4+1' technetium/rhenium mixed-ligand complexes open a new way to application of 99 mTc/ 188 Re labeled compounds in tumor diagnosis and therapy. In the presented paper, authors describe the synthesis and study of novel 99 mTc/ 188 Re complexes with dendritically functionalized tetradentate (tripodal chelator 2,2',2''-nitrilotris(ethanethiol), NS 3 and carboxyl group-bearing ligand, NS 3 (COOH) 3 ) and monodentate (dendritically modified isocyanide, CN-R(COOMe) 3 and isocyanide-modified peptide, CN-GGY) ligands. To verify the identity of the prepared n.c.a. complexes, non-radioactive analogous '4+1' Re compounds were synthesized. The experimental data show that a dendritic modification of the tetradentate/monodentate ligands changes the complex lipophilicity and does not influence its stability

An FEA study on impact resistance of bio-inspired CAD models

OpenAIRE

Page, T; Thorsteinsson, G

2017-01-01

The purpose of this paper is to explore the use of biomimetic methods in the design of armour systems. It focusses on biological structures found in nature that feature both rigid and flexible armours, analysing their structures and determining which are the most widely successful. A study was conducted on three bio-inspired structures built in Creo Parametric and tested using Finite Element Analysis (FEA) software to determine which structure had the best impact resistance. The study was con...

Finite element analysis and validation of dielectric elastomer actuators used for active origami

International Nuclear Information System (INIS)

McGough, Kevin; Ahmed, Saad; Frecker, Mary; Ounaies, Zoubeida

2014-01-01

The field of active origami explores the incorporation of active materials into origami-inspired structures in order to serve as a means of actuation. Active origami-inspired structures capable of folding into complex three-dimensional (3D) shapes have the potential to be lightweight and versatile compared to traditional methods of actuation. This paper details the finite element analysis and experimental validation of unimorph actuators. Actuators are fabricated by adhering layers of electroded dielectric elastomer (3M VHB F9473PC) onto a passive substrate layer (3M Magic Scotch Tape). Finite element analysis of the actuators simulates the electromechanical coupling of the dielectric elastomer under an applied voltage by applying pressures to the surfaces of the dielectric elastomer where the compliant electrode (conductive carbon grease) is present. 3D finite element analysis of the bending actuators shows that applying contact boundary conditions to the electroded region of the active and passive layers provides better agreement to experimental data compared to modeling the entire actuator as continuous. To improve the applicability of dielectric elastomer-based actuators for active origami-inspired structures, folding actuators are developed by taking advantage of localized deformation caused by a passive layer with non-uniform thickness. Two-dimensional analysis of the folding actuators shows that agreement to experimental data diminishes as localized deformation increases. Limitations of using pressures to approximate the electromechanical coupling of the dielectric elastomer under an applied electric field and additional modeling considerations are also discussed. (paper)

Arts-inspired students sync their assets to a nuts and bolts world: A career mentoring pilot progam

Science.gov (United States)

Hudson, Lynn

This research examined how students who are arts-inspired feel about their futures in a STEM-based work climate. Science, Technology, Engineering, and Math are the nuts and bolts, and in education today, the only avenue touted for our country and our students' success in this 21st century economy. This can be disconcerting to those interested in other fields, like the arts. This study was guided by the following questions in an effort to understand if our artists and arts-inspired students realize their options and importance in this 21st century climate. The pilot study was designed to help improve the students' perception of their abilities or self-efficacy in the STEM areas by introducing STEM professionals as mentors who designed hands-on activities that simulate work in the STEM fields. Research Questions: 1. Do arts-inspired students have an interest in a STEM career area prior to participating in the career mentoring program? 2. Does participation in a STEM career mentoring program improve student's self-efficacy in STEM fields? 3. Does participation in STEM career mentoring program increase student's interest in pursuing STEM-related careers? Lent, Brown and Hackett's Social Cognitive Career Theory and Daniel Pink's, "A Whole New Mind: Why Left-Brainers Will Rule the Future" were used as the theoretical framework for this study. Seventeen African-American girls who were enrolled in the "I AM COMPLETE" summer program participated in the pilot study. Data was collected from the College Foundation of North Carolina Career Interest Explorer and the STEM Career Interest Survey, which served as a pre and post-test. This pilot offered limited support for the hypothesis, however, career mentoring and opportunities for young people to experience careers, especially in the STEM areas must continue to grow. The role that the arts play in this process is pivotal in galvanizing females and minorities to join these professions. It is the hope of this researcher that the

Ligand and membrane-binding behavior of the phosphatidylinositol transfer proteins PITPα and PITPβ.

Science.gov (United States)

Baptist, Matilda; Panagabko, Candace; Cockcroft, Shamshad; Atkinson, Jeffrey

2016-12-01

Phosphatidylinositol transfer proteins (PITPs) are believed to be lipid transfer proteins because of their ability to transfer either phosphatidylinositol (PI) or phosphatidylcholine (PC) between membrane compartments, in vitro. However, the detailed mechanism of this transfer process is not fully established. To further understand the transfer mechanism of PITPs we examined the interaction of PITPs with membranes using dual polarization interferometry (DPI), which measures protein binding affinity on a flat immobilized lipid surface. In addition, a fluorescence resonance energy transfer (FRET)-based assay was also employed to monitor how quickly PITPs transfer their ligands to lipid vesicles. DPI analysis revealed that PITPβ had a higher affinity to membranes compared with PITPα. Furthermore, the FRET-based transfer assay revealed that PITPβ has a higher ligand transfer rate compared with PITPα. However, both PITPα and PITPβ demonstrated a preference for highly curved membrane surfaces during ligand transfer. In other words, ligand transfer rate was higher when the accepting vesicles were highly curved.

Analysis of glycoprotein E-selectin ligANDs on human and mouse marrow cells enriched for hematopoietic stem/progenitor cells

KAUST Repository

Merzaban, Jasmeen; Burdick, Monica M.; Gadhoum, Samah; Dagia, Nilesh M.; Chu, Julia T.; Fuhlbrigge, Robert C.; Sackstein, Robert D.

2011-01-01

Although well recognized that expression of E-selectin on marrow microvessels mediates osteotropism of hematopoietic stem/progenitor cells (HSPCs), our knowledge regarding the cognate E-selectin ligand(s) on HSPCs is incomplete. Flow cytometry using

Bexarotene ligand pharmaceuticals.

Science.gov (United States)

Hurst, R E

2000-12-01

Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response

Mechanistic pathways of recognition of a solvent-inaccessible cavity of protein by a ligand

Science.gov (United States)

Mondal, Jagannath; Pandit, Subhendu; Dandekar, Bhupendra; Vallurupalli, Pramodh

One of the puzzling questions in the realm of protein-ligand recognition is how a solvent-inaccessible hydrophobic cavity of a protein gets recognized by a ligand. We address the topic by simulating, for the first time, the complete binding process of benzene from aqueous media to the well-known buried cavity of L99A T4 Lysozyme at an atomistic resolution. Our multiple unbiased microsecond-long trajectories, which were completely blind to the location of target binding site, are able to unequivocally identify the kinetic pathways along which benzene molecule meanders across the solvent and protein and ultimately spontaneously recognizes the deeply buried cavity of L99A T4 Lysozyme at an accurate precision. Our simulation, combined with analysis based on markov state model and free energy calculation, reveals that there are more than one distinct ligand binding pathways. Intriguingly, each of the identified pathways involves the transient opening of a channel of the protein prior to ligand binding. The work will also decipher rich mechanistic details on unbinding kinetics of the ligand as obtained from enhanced sampling techniques.

LASSO-ligand activity by surface similarity order: a new tool for ligand based virtual screening.

Science.gov (United States)

Reid, Darryl; Sadjad, Bashir S; Zsoldos, Zsolt; Simon, Aniko

2008-01-01

Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening

Science.gov (United States)

Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko

2008-06-01

Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

4th International Conference on Innovations in Bio-Inspired Computing and Applications

CERN Document Server

Krömer, Pavel; Snášel, Václav

2014-01-01

This volume of Advances in Intelligent Systems and Computing contains accepted papers presented at IBICA2013, the 4th International Conference on Innovations in Bio-inspired Computing and Applications. The aim of IBICA 2013 was to provide a platform for world research leaders and practitioners, to discuss the full spectrum of current theoretical developments, emerging technologies, and innovative applications of Bio-inspired Computing. Bio-inspired Computing is currently one of the most exciting research areas, and it is continuously demonstrating exceptional strength in solving complex real life problems. The main driving force of the conference is to further explore the intriguing potential of Bio-inspired Computing. IBICA 2013 was held in Ostrava, Czech Republic and hosted by the VSB - Technical University of Ostrava.

Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc.