WorldWideScience

Sample records for attached molecular design

  1. Design of a Power Tool Attachment for Sawing Operation

    Directory of Open Access Journals (Sweden)

    Mayur Appaiah

    2015-07-01

    Full Text Available The Design of a Power Tool Attachment for Sawing Operation is discussed. First, the Target Specifications are established. The Design work is carried out, especially that of the Main Shaft and Support Tube. Calculations and Finite Element Analysis (FEA are also done. The Prototype is fabricated and assembled. The Testing of the prototype is done, by Sawing commercial plywood of maximum thickness 25mm. Weight of the Attachment is 1.3 kg, and the Machine is easy to use, benefitting unskilled users.

  2. Attached-sunspace designs: a nationwide economic appraisal

    Energy Technology Data Exchange (ETDEWEB)

    Roach, F.; Kirschner, C.

    1980-01-01

    Performance estimates for attached-sunspace passive solar heated residences have recently been incorporated into the Los Alamos/UNM EASE III model. These estimates are used to analyze the economic performance of a fixed dimension sunspace design when attached to a pre-existing single family residential unit. The sunspace is a passive design which can be easily and effectively adapted to a retrofit situation. Several key parameters are carefully evaluated for the sunspace retrofit design. These include loan or mortgage terms, ownership period, resale potential and competing conventional fuel prices. General economic and design parameters are combined in a variant of life cycle costing to evaluate the feasibility of both owner-built and contractor-built attached sunspaces for 220 regions in the contiguous United States. This evaluation is made for two conventional fuel types - natural gas and electric resistance - and for three resale values - 0%, 100%, and 200%. Results show that the prospect for conventional fuel displacement through retrofit of attached sunspaces is very good with the design's economic performance enhanced in regions with expensive conventional fuel alternatives.

  3. Dissociative electron attachment to CO2 produces molecular oxygen

    Science.gov (United States)

    Wang, Xu-Dong; Gao, Xiao-Fei; Xuan, Chuan-Jin; Tian, Shan Xi

    2016-03-01

    Until recently, it was widely regarded that only one reaction pathway led to the production of molecular oxygen in Earth's prebiotic primitive atmosphere: a three-body recombination reaction of two oxygen atoms and a third body that removes excess energy. However, an additional pathway has recently been observed that involves the photodissociation of CO2 on exposure to ultraviolet light. Here we demonstrate a further pathway to O2 production, again from CO2, but via dissociative electron attachment (DEA). Using anion-velocity image mapping, we provide experimental evidence for a channel of DEA to CO2 that produces O2(X3Σ-g) + C-. This observed channel coexists in the same energy range as the competitive three-body dissociation of CO2 to give O + O + C-. The abundance of low-energy electrons in interstellar space and the upper atmosphere of Earth suggests that the contributions of these pathways are significant and should be incorporated into atmospheric chemistry models.

  4. Design and Development of Attachment for Hydraulic Stacker

    Directory of Open Access Journals (Sweden)

    S.H. Gawande

    2010-05-01

    Full Text Available The main purpose of this paper is to develop an Attachment which will enable the lateral movement of the manufacturing Dies by mounting it on the forks of any Hydraulic Stacker or Fork Lift. The Attachmentmanufactured is unique because it can be attached or mounted on any hydraulic stalker in the One Tonne range. The attachment is a combination of two separate bed of rollers, a lead screw, a gear mechanism and a moving frame which enables the hydraulic stacker to easily load or unload Dies upto the range of one tonne, in and out of Machine Presses and Storage Racks which reduces material handling time and cost, manual effort and increases safety. The developed attachment in this work can also be easily detached and kept aside when not in use, so that the stacker can be used for regular purposes in the logistics department. The detail design, fabrication and testing work is carried out at A.V.M Seating Systems Ltd, Pune-26.

  5. Process for attaching molecular wires and devices to carbon nanotubes and compositions thereof

    Science.gov (United States)

    Tour, James M. (Inventor); Bahr, Jeffrey L. (Inventor); Yang, Jiping (Inventor)

    2008-01-01

    The present invention is directed towards processes for covalently attaching molecular wires and molecular electronic devices to carbon nanotubes and compositions thereof. Such processes utilize diazonium chemistry to bring about this marriage of wire-like nanotubes with molecular wires and molecular electronic devices.

  6. Integrating Emotional Attachment and Sustainability in Electronic Product Design

    Directory of Open Access Journals (Sweden)

    Alex Lobos

    2013-03-01

    Full Text Available Current models for Information and Communication Technology (ICT products encourage frequent product replacement with newer versions that offer only minor incremental improvements. This pattern, named planned obsolescence, diminishes user experience and shortens product lifespan. This paper presents the conceptual basis for a two-part integrated approach to combating planned obsolescence in ICT devices. First, design for emotional attachment, which creates products that users enjoy, value, and use for longer. Second, technological adaptability, which anticipates product upgrades and repairs as new technologies emerge. A model interdisciplinary design course in industrial design and sustainability, also described herein, trains students to apply this approach to create innovative ICT products with smaller environmental footprints.

  7. DESIGN OF A PORTABLE AND ATTACHABLE BABY COT

    Directory of Open Access Journals (Sweden)

    SOWAH BORIS NII-AKO

    2013-05-01

    Full Text Available To solve congestion problems facing many hospitals in developing countries, baby cots are being eliminated and mothers are made to sleep on the same bed with their new-born babies; a practice known as co-sleeping. The work presented here seeks to reduce risks of Sudden Infant Death Syndrome (SIDS and suffocation associated with co-sleeping by employing the formal engineering design process to develop a portable, safe and cost effective baby cot. The cot is attachable to the mother’s bed, has four movement restrictors to regulate the movement of the baby within a given range and a hard surface mattress to ensure the safety of the baby. There are ventilation ports provided to keep the temperature within the cot comfortable. The design can be modified to be used by older babies and may be mounted on a collapsible stand where space limitations are not critical.

  8. Structured attachment of bacterial molecular motors for defined microflow induction

    Directory of Open Access Journals (Sweden)

    Woerdemann Mike

    2014-01-01

    Full Text Available Bacterial rotational motor complexes that propel flagellated bacteria possess unique properties like their size of a few nanometres and the ability of selfreproduction that have led to various exciting applications including biohybrid nano-machines. One mandatory prerequisite to utilize bacterial nano motors in fluid applications is the ability to transfer force and torque to the fluid, which usually can be achieved by attachment of the bacterial cell to adequate surfaces. Additionally, for optimal transfer of force or torque, precise control of the position down to the single cell level is of utmost importance. Based on a PIV (particle image velocimetry evaluation of the induced flow of single bacteria,we propose and demonstrate attachment of arbitrary patterns of motile bacterial cells in a fast light-based two-step process for the first time to our knowledge. First, these cells are pre-structured by holographic optical tweezers and then attached to a homogeneous, polystyrene-coated surface. In contrast to the few approaches that have been implemented up to now and which rely on pre-structured surfaces, our scheme allows for precise control on a single bacterium level, is versatile, interactive and has low requirements with respect to the surface preparation.

  9. Mechanical design of mussel byssus: material yield enhances attachment strength

    Science.gov (United States)

    Bell; Gosline

    1996-01-01

    The competitive dominance of mussels in the wave-swept rocky intertidal zone is in part due to their ability to maintain a secure attachment. Mussels are tethered to the substratum by a byssus composed of numerous extracellular, collagenous threads secreted by the foot. Each byssal thread has three serially arranged parts: a corrugated proximal region, a smooth distal region and an adhesive plaque. This study examines the material and structural properties of the byssal threads of three mussel species: Mytilus californianus, M. trossulus, and M. galloprovincialis. Tensile tests in general reveal similar material properties among species: the proximal region has a lower initial modulus, a lower ultimate stress and a higher ultimate strain than the distal region. The distal region also yields at a stress well below its ultimate value. In whole thread tests, the proximal region and adhesive plaque are common sites of structural failure and are closely matched in strength, while the distal region appears to be excessively strong. We propose that the high strength of the distal region is the byproduct of a material designed to yield and extend before structural failure occurs. Experimental and theoretical evidence is presented suggesting that thread yield and extensibility provide two important mechanisms for increasing the overall attachment strength of the mussel: (1) the reorientation of threads towards the direction of applied load, and (2) the 'recruitment' of more threads into tension and the consequent distribution of applied load over a larger cross-sectional area, thereby reducing the stress on each thread. This distal region yield behavior is most striking for M. californianus and may be a key to its success in extreme wave-swept environments.

  10. Molecular beacon sequence design algorithm.

    Science.gov (United States)

    Monroe, W Todd; Haselton, Frederick R

    2003-01-01

    A method based on Web-based tools is presented to design optimally functioning molecular beacons. Molecular beacons, fluorogenic hybridization probes, are a powerful tool for the rapid and specific detection of a particular nucleic acid sequence. However, their synthesis costs can be considerable. Since molecular beacon performance is based on its sequence, it is imperative to rationally design an optimal sequence before synthesis. The algorithm presented here uses simple Microsoft Excel formulas and macros to rank candidate sequences. This analysis is carried out using mfold structural predictions along with other free Web-based tools. For smaller laboratories where molecular beacons are not the focus of research, the public domain algorithm described here may be usefully employed to aid in molecular beacon design.

  11. De novo molecular design

    CERN Document Server

    Schneider, Gisbert

    2013-01-01

    Systematically examining current methods and strategies, this ready reference covers a wide range of molecular structures, from organic-chemical drugs to peptides, Proteins and nucleic acids, in line with emerging new drug classes derived from biomacromolecules. A leader in the field and one of the pioneers of this young discipline has assembled here the most prominent experts from across the world to provide first-hand knowledge. While most of their methods and examples come from the area of pharmaceutical discovery and development, the approaches are equally applicable for chemical probes an

  12. Consumer-product attachment: measurement and design implications

    NARCIS (Netherlands)

    Schifferstein, H.N.J.; Zwartkruis-Pelgrim, E.P.H.

    2008-01-01

    Due to differences in the attachment consumers experience towards the durable products they own, they hang on to certain products whereas they easily dispose of others. From the viewpoint of sustainability, it may be worthwhile to lengthen the life span of many durable consumer products. Hence, ther

  13. Molecular design of allergy vaccines.

    Science.gov (United States)

    Linhart, Birgit; Valenta, Rudolf

    2005-12-01

    Recombinant-allergen-based diagnostic tests enable the dissection and monitoring of the molecular reactivity profiles of allergic patients, resulting in more specific diagnosis, disease monitoring, prevention and therapy. In vitro experiments, animal studies and clinical trials in patients demonstrate that allergenic molecules can be engineered to induce different immune responses ranging from tolerance to vigorous immunity. The available data thus suggest that molecular engineering of the disease-related antigens is a technology that may be applicable not only for the design of allergy vaccines but also for the design of vaccines against infectious diseases, autoimmunity and cancer.

  14. Rate coefficients for low-energy electron dissociative attachment to molecular hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Horacek, J.; Houfek, K.; Cizek, M. [Charles University, Faculty of Mathematics and Physics, Prague (Czech Republic); Murakami, I.; Kato, T. [National Inst. for Fusion Science, Toki, Gifu (Japan)

    2003-02-01

    Calculation of rate constants for dissociative electron attachment to molecular hydrogen is reported. The calculation is based on an improved nonlocal resonance model of Cizek, Horacek and Domcke which takes fully into account the nonlocality of the resonance dynamics and uses potentials with correct asymptotic forms. The rate constants are calculated for all quantum numbers v and J of the target molecules and for electron temperature in the range 0-30000 K. (author)

  15. Cob-Weaving Spiders Design Attachment Discs Differently for Locomotion and Prey Capture

    Science.gov (United States)

    Sahni, Vasav; Harris, Jared; Blackledge, Todd; Dhinojwala, Ali

    2013-03-01

    Spiders' cobwebs ensnare both walking and flying prey. While the scaffolding silk can entangle flying insects, gumfoot silk threads pull walking prey off the ground and into the web. Therefore, scaffolding silk needs to withstand the impact of the prey, whereas gumfoot silk needs to easily detach from the substrate when contacted by prey. Here, we show that spiders accomplish these divergent demands by creating attachment discs of two distinct architectures using the same pyriform silk. A ``staple-pin'' architecture firmly attaches the scaffolding silk to the substrate and a previously unknown ``dendritic'' architecture weakly attaches the gumfoot silk to the substrate. Gumfoot discs adhere weakly, triggering a spring-loaded trap, while the strong adhesion of scaffolding discs compels the scaffolding threads to break instead of detaching. We describe the differences in adhesion for these two architectures using tape-peeling models and design synthetic attachments that reveal important design principles for controlled adhesion. National Science Foundation

  16. Emergent strategies for inverse molecular design

    Institute of Scientific and Technical Information of China (English)

    BERATAN; David; N.

    2009-01-01

    Molecular design is essential and ubiquitous in chemistry,physics,biology,and material science.The immense space of available candidate molecules requires novel optimization strategies and algorithms for exploring the space and achieving efficient and effective molecular design.This paper summarizes the current progress toward developing practical theoretical optimization schemes for molecular design.In particular,we emphasize emergent strategies for inverse molecular design.Several representative design examples,based on recently developed strategies,are described to demonstrate the principles of inverse molecular design.

  17. Molecular design of Mycoplasma hominis Vaa adhesin

    DEFF Research Database (Denmark)

    Boesen, Thomas; Fedosova, Natalya U.; Kjeldgaard, Morten

    2001-01-01

    The variable adherence-associated (Vaa) adhesin of the opportunistic human pathogen Mycoplasma hominis is a surface-exposed, membrane-associated protein involved in the attachment of the bacterium to host cells. The molecular masses of recombinant 1 and 2 cassette forms of the protein determined...

  18. Superspreading: mechanisms and molecular design.

    Science.gov (United States)

    Theodorakis, Panagiotis E; Müller, Erich A; Craster, Richard V; Matar, Omar K

    2015-03-03

    The intriguing ability of certain surfactant molecules to drive the superspreading of liquids to complete wetting on hydrophobic substrates is central to numerous applications that range from coating flow technology to enhanced oil recovery. Despite significant experimental efforts, the precise mechanisms underlying superspreading remain unknown to date. Here, we isolate these mechanisms by analyzing coarse-grained molecular dynamics simulations of surfactant molecules of varying molecular architecture and substrate affinity. We observe that for superspreading to occur, two key conditions must be simultaneously satisfied: the adsorption of surfactants from the liquid-vapor surface onto the three-phase contact line augmented by local bilayer formation. Crucially, this must be coordinated with the rapid replenishment of liquid-vapor and solid-liquid interfaces with surfactants from the interior of the droplet. This article also highlights and explores the differences between superspreading and conventional surfactants, paving the way for the design of molecular architectures tailored specifically for applications that rely on the control of wetting.

  19. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlo Travaglini-Allocatelli

    2013-01-01

    Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

  20. On the dissociative electron attachment as a potential source of molecular hydrogen in irradiated liquid water

    Energy Technology Data Exchange (ETDEWEB)

    Cobut, V.; Jay-Gerin, J.-P.; Frongillo, Y. [Sherbrooke Univ., PQ (Canada). Faculte de Medecine; Patau, J.P. [Toulouse-3 Univ., 31 (France)

    1996-02-01

    In the radiolysis of liquid water, different mechanisms for the formation of molecular hydrogen (H{sub 2}) are involved at different times after the initial energy disposition. It has been suggested that the contributions of the e{sub aq}{sup -} + e{sub aq}{sup -}, H + e{sub aq}{sup -} and H + H reactions between hydrated electrons (e{sub aq}{sup -}) and hydrogen atoms in the spurs are not sufficient to account for all of the observed H{sub 2} yield (0.45 molecules/100 eV) on the microsecond time scale. Addressing the question of the origin of an unscavengeable H{sub 2} yield of 0.15 molecules/100 eV produced before spur expansion, we suggest that the dissociative capture of the so-called vibrationally-relaxing electrons by H{sub 2}O molecules is a possible pathway for the formation of part of the initial H{sub 2} yield. Comparison of recent dissociative-electron-attachment H{sup -}-anion yield-distribution measurements from amorphous H{sub 2}O films with the energy spectrum of vibrationally-relaxing electrons in irradiated liquid water, calculated by Monte Carlo simulations, plays in favor of this hypothesis. (author).

  1. Molecular phylogenetic analysis of attached Ulvaceae species and free-floating Enteromorpha from Qingdao coasts in 2007

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Based on the sequence data of the nuclear ribosomal DNA internal transcribed spacer (ITS) 1, 5.8 S, and ITS 2, the molecular phylogeny was analyzed on Ulvaceae species collected from Qingdao coasts in summer of 2007, including 15 attached Ulva and Enteromorpha samples from 10 locations and 10 free-floating Enteromorpha samples from seven locations. The result supported the monophyly of all free-floating Enteromorpha samples, implying the unialgal composition of the free-floating Enteromorpha, and the attached Ulvaceae species from Qingdao coasts were grouped into other five clades, suggesting that they were not the biogeographic origin of the free-floating Enteromorpha in that season.

  2. A finite element study on stress distribution of two different attachment designs under implant supported overdenture

    Directory of Open Access Journals (Sweden)

    Mohamed I. El-Anwar

    2015-10-01

    Conclusions: Locator and ball and socket attachments induce equivalent stresses on bone surrounding implants. Locator attachment performance was superior to that of the ball and socket attachment in the implants, nylon caps, and overdenture. Locator attachments are highly recommended and can increase the interval between successive maintenance sessions.

  3. Solvent effects in thermal electron attachment to clusters containing molecular oxygen

    Science.gov (United States)

    Desfrançois, Ch.; Schermann, J. P.

    1993-03-01

    Thermal electron attachment to oxygen is strongly modified when this molecule is bound in heterogenous van der Waals clusters. With the help of a laser-excited Rydberg electron source, we investigate the influence upon electron capture of the solvent nature by comparing O2(H2O)N and O2(C6H6)N attachment rate constants, and we observe size effects down to nearly zero energy.

  4. Molecular catalysts structure and functional design

    CERN Document Server

    Gade, Lutz H

    2014-01-01

    Highlighting the key aspects and latest advances in the rapidly developing field of molecular catalysis, this book covers new strategies to investigate reaction mechanisms, the enhancement of the catalysts' selectivity and efficiency, as well as the rational design of well-defined molecular catalysts. The interdisciplinary author team with an excellent reputation within the community discusses experimental and theoretical studies, along with examples of improved catalysts, and their application in organic synthesis, biocatalysis, and supported organometallic catalysis. As a result, readers wil

  5. Molecular Nanotechnology and Designs of Future

    Science.gov (United States)

    Srivastava, Deepak; Chancellor, Marisa K. (Technical Monitor)

    1997-01-01

    Reviewing the status of current approaches and future projections, as already published in the scientific journals and books, the talk will summarize the direction in which computational and experimental molecular nanotechnologies are progressing. Examples of nanotechnological approach to the concepts of design and simulation of atomically precise materials in a variety of interdisciplinary areas will be presented. The concepts of hypothetical molecular machines and assemblers as explained in Drexler's and Merckle's already published work and Han et. al's WWW distributed molecular gears will be explained.

  6. Prevalence and first molecular characterization of Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, in Rhipicephalus sanguineus ticks attached to dogs from Egypt

    Directory of Open Access Journals (Sweden)

    Mohamed W. Ghafar

    2012-04-01

    Full Text Available PCR targeting 16S rRNA gene integrated with sequence analysis were performed to investigate the prevalence and the molecular identity of Anaplasma phagocytophilum in Egyptian Rhipicephalus sanguineus ticks attached to dogs. A total of 413 adult and nymphal R. sanguineus ticks were collected while attached to 72 free-roaming dogs from four locations (Imbaba, Boulaq, Haram, Monib in Giza Governorate, Egypt. DNA was successfully extracted from 401 specimens (133 nymphs and 268 adults. The overall prevalence rate was 13.7% and adult ticks showed a significantly higher infection rate (16.4% compared to nymphs (8.3%. Sequence comparisons of 218-bp showed that detected organism belongs to A. phagocytophilum. The sequence showed 99.1% similarity (2 nucleotide differences with some strains described as human pathogens and with that detected in the established tick vectors. Phylogenetic analysis placed the bacteria on a separate branch with that found in R. annulatus from Egypt (DQ379972 (99.5% similarity. Our variant strain was designated as A. phagocytophilum-Ghafar-EGY (AB608266. This report is the first molecular characterization of A. phagocytophilum in R. sanguineus in Egypt, suggesting that this tick species may act as a competent vector for a variant strain of human granulocytic anaplasmosis agent.

  7. Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71.

    Science.gov (United States)

    Dang, Minghao; Wang, Xiangxi; Wang, Quan; Wang, Yaxin; Lin, Jianping; Sun, Yuna; Li, Xuemei; Zhang, Liguo; Lou, Zhiyong; Wang, Junzhi; Rao, Zihe

    2014-09-01

    Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.

  8. Molecular understanding and design of zwitterionic materials.

    Science.gov (United States)

    Shao, Qing; Jiang, Shaoyi

    2015-01-01

    Zwitterionic materials have moieties possessing cationic and anionic groups. This molecular structure leads to unique properties that can be the solutions of various application problems. A typical example is that zwitterionic carboxybetaine (CB) and sulfobetaine (SB) materials resist nonspecific protein adsorption in complex media. Considering the vast number of cationic and anionic groups in the current chemical inventory, there are many possible structural variations of zwitterionic materials. The diversified structures provide the possibility to achieve many desired properties and urge a better understanding of zwitterionic materials to provide design principles. Molecular simulations and modeling are a versatile tool to understand the structure-property relationships of materials at the molecular level. This progress report summarizes recent simulation and modeling studies addressing two fundamental questions regarding zwitterionic materials and their applications as biomaterials. First, what are the differences between zwitterionic and nonionic materials? Second, what are the differences among zwitterionic materials? This report also demonstrates a molecular design of new protein-resistant zwitterionic moieties beyond conventional CB and SB based on design principles developed from these simulation studies.

  9. Molecular Rift: Virtual Reality for Drug Designers.

    Science.gov (United States)

    Norrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Boström, Jonas

    2015-11-23

    Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub.

  10. Prevalence and first molecular characterization of Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, in Rhipicephalus sanguineus ticks attached to dogs from Egypt

    OpenAIRE

    Mohamed W. Ghafar; Sayed A. Amer

    2012-01-01

    PCR targeting 16S rRNA gene integrated with sequence analysis were performed to investigate the prevalence and the molecular identity of Anaplasma phagocytophilum in Egyptian Rhipicephalus sanguineus ticks attached to dogs. A total of 413 adult and nymphal R. sanguineus ticks were collected while attached to 72 free-roaming dogs from four locations (Imbaba, Boulaq, Haram, Monib) in Giza Governorate, Egypt. DNA was successfully extracted from 401 specimens (133 nymphs and 268 adults). The over...

  11. Application of Targeted Molecular and Material Property Optimization to Bacterial Attachment-Resistant (Meth)acrylate Polymers.

    Science.gov (United States)

    Adlington, Kevin; Nguyen, Nam T; Eaves, Elizabeth; Yang, Jing; Chang, Chien-Yi; Li, Jianing; Gower, Alexandra L; Stimpson, Amy; Anderson, Daniel G; Langer, Robert; Davies, Martyn C; Hook, Andrew L; Williams, Paul; Alexander, Morgan R; Irvine, Derek J

    2016-09-12

    Developing medical devices that resist bacterial attachment and subsequent biofilm formation is highly desirable. In this paper, we report the optimization of the molecular structure and thus material properties of a range of (meth)acrylate copolymers which contain monomers reported to deliver bacterial resistance to surfaces. This optimization allows such monomers to be employed within novel coatings to reduce bacterial attachment to silicone urinary catheters. We show that the flexibility of copolymers can be tuned to match that of the silicone catheter substrate, by copolymerizing these polymers with a lower Tg monomer such that it passes the flexing fatigue tests as coatings upon catheters, that the homopolymers failed. Furthermore, the Tg values of the copolymers are shown to be readily estimated by the Fox equation. The bacterial resistance performance of these copolymers were typically found to be better than the neat silicone or a commercial silver containing hydrogel surface, when the monomer feed contained only 25 v% of the "hit" monomer. The method of initiation (either photo or thermal) was shown not to affect the bacterial resistance of the copolymers. Optimized synthesis conditions to ensure that the correct copolymer composition and to prevent the onset of gelation are detailed.

  12. Molecular design and QSARs/QSPRs with molecular descriptors family.

    Science.gov (United States)

    Bolboacă, Sorana D; Jäntschi, Lorentz; Diudea, Mircea V

    2013-06-01

    The aim of the present paper is to present the methodology of the molecular descriptors family (MDF) as an integrative tool in molecular modeling and its abilities as a multivariate QSAR/QSPR modeling tool. An algorithm for extracting useful information from the topological and geometrical representation of chemical compounds was developed and integrated to calculate MDF members. The MDF methodology was implemented and the software is available online (http://l.academicdirect.org/Chemistry/SARs/MDF_SARs/). This integrative tool was developed in order to maximize performance, functionality, efficiency and portability. The MDF methodology is able to provide reliable and valid multiple linear regression models. Furthermore, in many cases, the MDF models were better than the published results in the literature in terms of correlation coefficients (statistically significant Steiger's Z test at a significance level of 5%) and/or in terms of values of information criteria and Kubinyi function. The MDF methodology developed and implemented as a platform for investigating and characterizing quantitative relationships between the chemical structure and the activity/property of active compounds was used on more than 50 study cases. In almost all cases, the methodology allowed obtaining of QSAR/QSPR models improved in explanatory power of structure-activity and structure-property relationships. The algorithms applied in the computation of geometric and topological descriptors (useful in modeling physicochemical or biological properties of molecules) and those used in searching for reliable and valid multiple linear regression models certain enrich the pool of low-cost low-time drug design tools.

  13. Design of 8-ft-Diameter Barrel Test Article Attachment Rings for Shell Buckling Knockdown Factor Project

    Science.gov (United States)

    Lovejoy, Andrew E.; Hilburger, Mark W.

    2010-01-01

    The Shell Buckling Knockdown Factor (SBKF) project includes the testing of sub-scale cylinders to validate new shell buckling knockdown factors for use in the design of the Ares-I and Ares-V launch vehicles. Test article cylinders represent various barrel segments of the Ares-I and Ares-V vehicles, and also include checkout test articles. Testing will be conducted at Marshall Space Flight Center (MSFC) for test articles having an eight-foot diameter outer mold line (OML) and having lengths that range from three to ten feet long. Both ends of the test articles will be connected to the test apparatus using attachment rings. Three multiple-piece and one single-piece design for the attachment rings were developed and analyzed. The single-piece design was chosen and will be fabricated from either steel or aluminum (Al) depending on the required safety factors (SF) for test hardware. This report summarizes the design and analysis of these attachment ring concepts.

  14. Molecular examinations of Babesia microti in rodents and rodent-attached ticks from urban and sylvatic habitats in Germany.

    Science.gov (United States)

    Obiegala, Anna; Pfeffer, Martin; Pfister, Kurt; Karnath, Carolin; Silaghi, Cornelia

    2015-06-01

    Small mammals serve as reservoir hosts for tick-borne pathogens, especially for those which are not transmitted transovarially in ticks - such as Babesia microti. Molecular investigations on the prevalence of B. microti in wild small mammals and on attached ticks from differently structured areas may provide information on the circulation of B. microti in different ecological niches. In 2012 and 2013, 622 rodents (396 Myodes glareolus, 178 Apodemus flavicollis, 36 Apodemus sylvaticus, 4 Apodemus agrarius, 7 Microtus arvalis, 1 Microtus agrestis) were captured from three differently structured habitats (urban, sylvatic, recultivated) in Germany. Attached ticks were collected from 449 small mammals (3250 Ixodes ricinus, 7 Ixodes trianguliceps, 133 Dermacentor reticulatus). A representative selection of a maximum of 5 ticks per developmental stage and species per 30 rodents of each species, location and year resulting in 965 ticks was further investigated. DNA was extracted from tick, blood and spleen samples, and tested by PCR for the partial 18S rRNA gene of B. microti with subsequent sequencing. The prevalence was significantly higher in rodents from the sylvatic site (4.6%) than in rodents captured at both other sites (-0.6%) (χ(2)=11.95; p=0.00125). Body and spleen weight of infected M. glareolus from the sylvatic site were significantly higher compared to those from non-infected individuals from that site (p=0.00288 and p=0.00017, respectively). Babesia microti DNA was detected in 3 out of 965 attached ticks (0.3%; 95%CI: 0-1) from all sites, but they derived exclusively from rodents captured at the sylvatic site. At the same site, I. ricinus nymphs (7.7%; 95%CI: 1-25.3) were significantly more often infected than I. ricinus larvae (0%; 95%CI: 0-1.3)(χ(2)=26.72; prodents was also found at that site. I. trianguliceps occurred exclusively and the majority of M. glareolus at that site. Thus, it may be assumed that the circulation of B. microti is more efficient

  15. Bio-inspired novel design principles for artificial molecular motors.

    Science.gov (United States)

    Hugel, Thorsten; Lumme, Christina

    2010-10-01

    Since we have learned that biological organisms like ourselves are driven by tiny biological molecular motors we try to design and produce artificial molecular motors. However, despite the huge efforts since decades, man-made artificial molecular motors are still far from biological molecular motors or macroscopic motors with regard to performance, especially with respect to energy efficiency. This review highlights recent progress towards artificial molecular motors and discusses how their design and development can be guided by the design concepts of biological molecular motors or macroscopic motors.

  16. Metalloporphyrin catalysts for oxygen reduction developed using computer-aided molecular design

    Energy Technology Data Exchange (ETDEWEB)

    Ryba, G.N.; Hobbs, J.D.; Shelnutt, J.A. [and others

    1996-04-01

    The objective of this project is the development of a new class of metalloporphyrin materials used as catalsyts for use in fuel cell applications. The metalloporphyrins are excellent candidates for use as catalysts at both the anode and cathode. The catalysts reduce oxygen in 1 M potassium hydroxide, as well as in 2 M sulfuric acid. Covalent attachment to carbon supports is being investigated. The computer-aided molecular design is an iterative process, in which experimental results feed back into the design of future catalysts.

  17. Direct attachment of nanoparticle cargo to Salmonella typhimurium membranes designed for combination bacteriotherapy against tumors.

    Science.gov (United States)

    Kazmierczak, Robert; Choe, Elizabeth; Sinclair, Jared; Eisenstark, Abraham

    2015-01-01

    Nanoparticle technology is an emerging approach to resolve difficult-to-manage internal diseases. It is highly regarded, in particular, for medical use in treatment of cancer due to the innate ability of certain nanoparticles to accumulate in the porous environment of tumors and to be toxic to cancer cells. However, the therapeutic success of nanoparticles is limited by the technical difficulty of fully penetrating and thus attacking the tumor. Additionally, while nanoparticles possess seeming-specificity due to the unique physiological properties of tumors themselves, it is difficult to tailor the delivery of nanoparticles or drugs in other models, such as use in cardiac disease, to the specific target. Thus, a need for delivery systems that will accurately and precisely bring nanoparticles carrying drug payloads to their intended sites currently exists. Our solution to this engineering challenge is to load such nanoparticles onto a biological "mailman" (a novel, nontoxic, therapeutic strain of Salmonella typhimurium engineered to preferentially and precisely seek out, penetrate, and hinder prostate cancer cells as the biological delivery system) that will deliver the therapeutics to a target site. In this chapter, we describe two methods that establish proof-of-concept for our cargo loading and delivery system by attaching nanoparticles to the Salmonella membrane. The first method (Subheading 1.1) describes association of sucrose-conjugated gold nanoparticles to the surface of Salmonella bacteria. The second method (Subheading 1.2) biotinylates the native Salmonella membrane to attach streptavidin-conjugated fluorophores as example nanoparticle cargo, with an alternative method (expression of membrane bound biotin target sites using autodisplay plasmid vectors) that increases the concentration of biotin on the membrane surface for streptavidin-conjugated nanoparticle attachment. By directly attaching the fluorophores to our bacterial vector through biocompatible

  18. Design of a directed molecular network.

    Science.gov (United States)

    Ashkenasy, Gonen; Jagasia, Reshma; Yadav, Maneesh; Ghadiri, M Reza

    2004-07-27

    An ability to rationally design complex networks from the bottom up can offer valuable quantitative model systems for use in gaining a deeper appreciation for the principles governing the self-organization and functional characteristics of complex systems. We report herein the de novo design, graph prediction, experimental analysis, and characterization of simple self-organized, nonlinear molecular networks. Our approach makes use of the sequence-dependent auto- and cross-catalytic functional characteristics of template-directed peptide fragment condensation reactions in neutral aqueous solutions. Starting with an array of 81 sequence similar 32-residue coiled-coil peptides, we estimated the relative stability difference between all plausible A(2)B-type coiled-coil ensembles and used this information to predict the auto- and cross-catalysis pathways and the resulting plausible network motif and connectivities. Similar to most complex systems, the generated graph displays clustered nodes with an overall hierarchical architecture. To test the validity of the design principles used, nine nodes composing a main segment of the graph were experimentally analyzed for their capacity in establishing the predicted network connectivity. The resulting self-organized chemical network is shown to display 25 directed edges in good agreement with the graph analysis estimations. Moreover, we show that by varying the system parameters (presence or absence of certain substrates or templates), its operating network motif can be altered, even to the extremes of turning pathways on or off. We suggest that this approach can be expanded for the construction of large-scale networks, offering a means to study and to understand better the emergent, collective behaviors of networks.

  19. A Strong Inference Investigation of the Job Characteristics and Dual Attachment Models of Job Design

    Science.gov (United States)

    1984-02-01

    reported to have occurred during the first 3 weeks of implementation. Job design intervention was assigned to two conditions: both the job design only...treatment conditions included job design intervention , leader-member exchange intervention, combined design and exchange intervention and control or...during the criterion period (weeks 15 to 26). The other two grnups, group 2 (job design intervention ) and group 1 (both leadership .2nd *. job design

  20. Brownian molecular rotors: Theoretical design principles and predicted realizations

    Science.gov (United States)

    Schönborn, Jan Boyke; Herges, Rainer; Hartke, Bernd

    2009-06-01

    We propose simple design concepts for molecular rotors driven by Brownian motion and external photochemical switching. Unidirectionality and efficiency of the motion is measured by explicit simulations. Two different molecular scaffolds are shown to yield viable molecular rotors when decorated with suitable substituents.

  1. Beneficial design of unbaffled shell-and-tube heat exchangers for attachment of longitudinal fins with trapezoidal profile

    Directory of Open Access Journals (Sweden)

    Balaram Kundu

    2015-03-01

    Full Text Available A parametric variation followed with Kern’s method of design of extended surface heat exchanger has been made for an unbaffled shell-and-tube heat exchanger problem. For this analysis, the rectangular and trapezoidal fin shapes longitudinally attached to the fin tubes are taken. In comparison with the attachment of trapezoidal fins, it is found that the heat transfer rate was lesser than the rectangular cross section by keeping a constant outer diameter of the shell along with all other constraints of a heat exchanger design, namely, number of passes, tube outer diameter, tube pitch layout, etc. But when the total volume of the fin over a tube was kept constraint, using trapezoidal fins the heat transfer rate is found to be increased and consequently the pressure drop decreases much more than in the case of fins with rectangular cross section. This optimization has shown beneficial results in all the cases of different constraints of heat exchanger design analysis.

  2. Protein attachment onto silica surfaces--a survey of molecular fundamentals, resulting effects and novel preventive strategies in CE.

    Science.gov (United States)

    Stutz, Hanno

    2009-06-01

    This review addresses the fundamentals governing the adsorption of individual protein molecules onto the surface of fused-silica capillaries, the protein aggregation to adsorbate clusters and their final accretion to monolayers with subsequent stratification to protein multilayers. The attention in CE protein separation has primarily been focused on (i) tuning the BGE including the buffer type, ionic strength, pH and additives, (ii) tailored post-rinse procedures to detach adhered protein residues and (iii) the optimization of capillary wall shielding in order to reduce protein attachment. Improvements in protein separation as well as related adverse effects are mainly discussed on the basis of parameters known to become deteriorated in case of protein adhesion, e.g. repeatability of the EOF and of migration times, peak width, theoretical plate numbers, resolution and asymmetry factor. However, knowledge of the molecular principles controlling protein adsorption onto silica surfaces is indispensable for separation optimization. Furthermore, it facilitates troubleshooting and the interpretation of undesired concomitant phenomena. This review comprehensively discusses protein adsorption models derived from surface chemistry primarily in terms of their relevance for CE, clearly showing that the adsorption process in its complexity is only partially revealed by models, which address single or binary protein solutions. In a further section theoretical concepts and surface models are related to surface phenomena encountered in CE. The final part of the review surveys recent concepts for prevention of protein adhesion, thereby addressing capillary treatment, favorable buffer types, dynamic and adhesive semi-permanent coating strategies covering the literature from 2000-2008.

  3. A quantum chemical study from a molecular perspective: ionization and electron attachment energies for species often used to fabricate single-molecule junctions

    CERN Document Server

    Baldea, Ioan

    2015-01-01

    The accurate determination of the lowest electron attachment ($EA$) and ionization ($IP$) energies for molecules embedded in molecular junctions is important for correctly estimating, \\emph{e.g.}, the magnitude of the currents ($I$) or the biases ($V$) where an $I-V$-curve exhibits a significant non-Ohmic behavior. Benchmark calculations for the lowest electron attachment and ionization energies of several typical molecules utilized to fabricate single-molecule junctions characterized by n-type conduction (4,4'-bipyridine, 1,4-dicyanobenzene, and 4,4'-dicyano-1,1'-biphenyl) and p-type conduction (benzenedithiol, biphenyldithiol, hexanemonothiol, and hexanedithiol] based on the EOM-CCSD (equation-of-motion coupled-cluster singles and doubles) state-of-the-art method of quantum chemistry are presented. They indicate significant differences from the results obtained within current approaches to molecular transport. The present study emphasizes that, in addition to a reliable quantum chemical method, basis sets m...

  4. Design and Application of Surface Modification at Molecular Scale

    Institute of Scientific and Technical Information of China (English)

    CHEN Miao; XUE Qun-Ji; ZHOU Feng; GUAN Fei; LIU Wei-Min

    2004-01-01

    The structuring of surfaces on a nanoscale level-both chemically and topographically has become an increasingly relevant field of research in nanotechnology with widespread application potential in various fields of science ( e. g.surface engineering, electronics, biotechnology, optics). Two examples on surface modification at molecular scale with self-assembly monolayers are shown: ( 1 ) Chemically attaching ultra-thin polymer films through the self-assembly of silane fictionalized copolymer have been approved in this article. (2) The patterned films with microstructures on different substrates have been prepared through micro-contact printing technique and electro polymerization.

  5. Synthesis of bis-peptides attached on poly[n]norbornene molecular scaffolds with well-defined relative positions and distances.

    Science.gov (United States)

    Shang, Muhong; Warrener, Ronald N; Butler, Douglas N; Murata, Yasujiro; Margetić, Davor

    2011-05-01

    This article describes novel synthetic approaches to polynorbornene molecular scaffolds substituted with peptides at various, well-defined positions. A library of norbornene building blocks with attached peptides was prepared. Alkene cyclobutane epoxide (ACE) coupling method was used as a key step reaction for the connection of two norbornene building blocks into bis-peptide scaffolds. Photodimerization of cyclobutene diesters offers an alternative route to polynorbornene bis-peptides. Pyrrolo-peptides were used for preparation of peptide-substituted 7-aza norbornenes. Asymmetrical bis-peptide scaffolds were prepared by ACE coupling of peptide-norbornane epoxide with another norbornene-peptide block. Chemical elaboration of bridgehead dimethyl esters of ACE products or epoxide ACE reagents was also used for peptide attachment.

  6. An Investigation into the Effects of Sprue Attachment Design on Porosity and Castability

    Science.gov (United States)

    1990-12-01

    Cardenas (Research Associate) for his assistance in laboratory analysis. My sincere gratitude is extended to Mr. Paul Cascone (Vice President, Research...10 mr --- - - - 32 taper of the master die were similar to those of Philp and Brukl (1984) and Verrett and Duke (1989). Utilization of a knife...order to obtain standardized wax patterns the specially designed sculpturing device (Plate 1) as described by Philp and Brukl (1984) and employed by

  7. De novo designed coiled-coil proteins with variable conformations as components of molecular electronic devices.

    Science.gov (United States)

    Shlizerman, Clara; Atanassov, Alexander; Berkovich, Inbal; Ashkenasy, Gonen; Ashkenasy, Nurit

    2010-04-14

    Conformational changes of proteins are widely used in nature for controlling cellular functions, including ligand binding, oligomerization, and catalysis. Despite the fact that different proteins and artificial peptides have been utilized as electron-transfer mediators in electronic devices, the unique propensity of proteins to switch between different conformations has not been used as a mechanism to control device properties and performance. Toward this aim, we have designed and prepared new dimeric coiled-coil proteins that adopt different conformations due to parallel or antiparallel relative orientations of their monomers. We show here that controlling the conformation of these proteins attached as monolayers to gold, which dictates the direction and magnitude of the molecular dipole relative to the surface, results in quantitative modulation of the gold work function. Furthermore, charge transport through the proteins as molecular bridges is controlled by the different protein conformations, producing either rectifying or ohmic-like behavior.

  8. Molecular Thermodynamics for Chemical Process Design

    Science.gov (United States)

    Prausnitz, J. M.

    1976-01-01

    Discusses that aspect of thermodynamics which is particularly important in chemical process design: the calculation of the equilibrium properties of fluid mixtures, especially as required in phase-separation operations. (MLH)

  9. The neurobiology of attachment.

    Science.gov (United States)

    Insel, T R; Young, L J

    2001-02-01

    It is difficult to think of any behavioural process that is more intrinsically important to us than attachment. Feeding, sleeping and locomotion are all necessary for survival, but humans are, as Baruch Spinoza famously noted, "a social animal" and it is our social attachments that we live for. Over the past decade, studies in a range of vertebrates, including humans, have begun to address the neural basis of attachment at a molecular, cellular and systems level. This review describes some of the important insights from this work.

  10. Participatory Design to Enhance ICT Learning and Community Attachment: A Case Study in Rural Taiwan

    Directory of Open Access Journals (Sweden)

    Yi-Ting Huang

    2015-03-01

    Full Text Available This study used observation and interviews with participants in “PunCar Action” to understand how participatory design methods can be applied to the education of rural individuals in information and communication technology (ICT. PunCar Action is a volunteer program in which ICT educators tour the rural communities of Taiwan, offering courses on the use of digital technology. This paper makes three contributions: First, we found that participatory design is an excellent way to teach ICT and Web 2.0 skills, co-create community blogs, and sustain intrinsic motivation to use Web applications. Second, PunCar Action provides an innovative bottom-up intergenerational ICT education model with high penetrability capable of enhancing the confidence of rural residents in the use of ICT. Third, the content of basic courses was based on applications capable of making the lives of elderly individuals more convenient, and the advanced course was based on the co-creation of community blogs aimed at reviving the core functions of communities and expanding local industry. Our research was conducted with the use of a non-quantitative index to measure ICT learning performance of participants from a rural community. The results show that PunCar Action emphasizes interpersonal communication and informational applications and creates a collaborative process that encourages rural residents to take action to close the digital divide.

  11. Computer aided molecular design with combined molecular modeling and group contribution

    DEFF Research Database (Denmark)

    Harper, Peter Mathias; Gani, Rafiqul; Kolar, Petr

    1999-01-01

    Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures and on th...

  12. Web Based Learning Support for Experimental Design in Molecular Biology.

    Science.gov (United States)

    Wilmsen, Tinri; Bisseling, Ton; Hartog, Rob

    An important learning goal of a molecular biology curriculum is a certain proficiency level in experimental design. Currently students are confronted with experimental approaches in textbooks, in lectures and in the laboratory. However, most students do not reach a satisfactory level of competence in the design of experimental approaches. This…

  13. MOLECULAR THERMODYNAMICS IN THE DESIGN OF SUBSTITUTE SOLVENTS

    Science.gov (United States)

    The use of physical properties and fluid behavior from molecular thermodynamics can lead to better decision making in the design of substitute solvents and can greatly reduce the expense and time required to find substitutes compared to designing solvents by experiment. this pape...

  14. Distribution of lifetimes of kinetochore-microtubule attachments:interplay of energy landscape, molecular motors and microtubule (de-)polymerization

    CERN Document Server

    Sharma, Ajeet K; Chowdhury, Debashish

    2013-01-01

    Before a cell divides into two daughter cells, the chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an {\\it in-vitro} experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed "catch-bond-like" behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the {\\it in-vitro} experiments provided the experiment is...

  15. Product Attachment

    NARCIS (Netherlands)

    Mugge, R.

    2007-01-01

    The topic of this doctoral research is the concept of product attachment for ordinary consumer durables. Product attachment is defined as the strength of the emotional bond a consumer experiences with a specific product. Specifically, the research investigated how this bond develops over time and th

  16. MOLECULAR DESIGN OF COLLOIDS IN SUPERCRITICAL FLUIDS

    Energy Technology Data Exchange (ETDEWEB)

    Keith P. Johnston

    2009-04-06

    The environmentally benign, non-toxic, non-flammable fluids water and carbon dioxide (CO2) are the two most abundant and inexpensive solvents on earth. Emulsions of these fluids are of interest in many industrial processes, as well as CO2 sequestration and enhanced oil recovery. Until recently, formation of these emulsions required stabilization with fluorinated surfactants, which are expensive and often not environmentally friendly. In this work we overcame this severe limitation by developing a fundamental understanding of the properties of surfactants the CO2-water interface and using this knowledge to design and characterize emulsions stabilized with either hydrocarbon-based surfactants or nanoparticle stabilizers. We also discovered a new concept of electrostatic stabilization for CO2-based emulsions and colloids. Finally, we were able to translate our earlier work on the synthesis of silicon and germanium nanocrystals and nanowires from high temperatures and pressures to lower temperatures and ambient pressure to make the chemistry much more accessible.

  17. Applicability of linearized-theory attached-flow methods to design and analysis of flap systems at low speeds for thin swept wings with sharp leading edges

    Science.gov (United States)

    Carlson, Harry W.; Darden, Christine M.

    1987-01-01

    Low-speed experimental force and data on a series of thin swept wings with sharp leading edges and leading and trailing-edge flaps are compared with predictions made using a linearized-theory method which includes estimates of vortex forces. These comparisons were made to assess the effectiveness of linearized-theory methods for use in the design and analysis of flap systems in subsonic flow. Results demonstrate that linearized-theory, attached-flow methods (with approximate representation of vortex forces) can form the basis of a rational system for flap design and analysis. Even attached-flow methods that do not take vortex forces into account can be used for the selection of optimized flap-system geometry, but design-point performance levels tend to be underestimated unless vortex forces are included. Illustrative examples of the use of these methods in the design of efficient low-speed flap systems are included.

  18. A systematic molecular circuit design method for gene networks under biochemical time delays and molecular noises

    Directory of Open Access Journals (Sweden)

    Chang Yu-Te

    2008-11-01

    Full Text Available Abstract Background Gene networks in nanoscale are of nonlinear stochastic process. Time delays are common and substantial in these biochemical processes due to gene transcription, translation, posttranslation protein modification and diffusion. Molecular noises in gene networks come from intrinsic fluctuations, transmitted noise from upstream genes, and the global noise affecting all genes. Knowledge of molecular noise filtering and biochemical process delay compensation in gene networks is crucial to understand the signal processing in gene networks and the design of noise-tolerant and delay-robust gene circuits for synthetic biology. Results A nonlinear stochastic dynamic model with multiple time delays is proposed for describing a gene network under process delays, intrinsic molecular fluctuations, and extrinsic molecular noises. Then, the stochastic biochemical processing scheme of gene regulatory networks for attenuating these molecular noises and compensating process delays is investigated from the nonlinear signal processing perspective. In order to improve the robust stability for delay toleration and noise filtering, a robust gene circuit for nonlinear stochastic time-delay gene networks is engineered based on the nonlinear robust H∞ stochastic filtering scheme. Further, in order to avoid solving these complicated noise-tolerant and delay-robust design problems, based on Takagi-Sugeno (T-S fuzzy time-delay model and linear matrix inequalities (LMIs technique, a systematic gene circuit design method is proposed to simplify the design procedure. Conclusion The proposed gene circuit design method has much potential for application to systems biology, synthetic biology and drug design when a gene regulatory network has to be designed for improving its robust stability and filtering ability of disease-perturbed gene network or when a synthetic gene network needs to perform robustly under process delays and molecular noises.

  19. Plasmon enhanced molecular absorption: A mixed quantum–classical description of supramolecular complexes attached to a metal nanoparticle

    Energy Technology Data Exchange (ETDEWEB)

    Megow, Jörg, E-mail: megow@physik.hu-berlin.de; May, Volkhard, E-mail: may@physik.hu-berlin.de

    2014-01-15

    Highlights: • Enhancement of molecular absorption was shown for J-aggregate-like coupling between molecules and MNP. • A large number of molecules is required in order to observe the molecular absorption. • Pheos Qx-band coupling to the plasmon resonance is hardly observable in the spectrum. - Abstract: The application of a mixed quantum–classical methodology for an investigation of single pheophorbide-a molecules (Pheos) and respective supramolecular complexes is continued to effects caused by a nearby placed metal nanoparticle (MNP). Therefore, the classical simulation of the molecular nuclear degrees of freedom is combined with a uniform quantum description of the molecular electronic excitations coupled to those of the MNP. To account for the short MNP plasmon life time the quantum dynamics of the electronic degrees of freedom is formulated in the framework of a system-bath theory. Linear absorption spectra are calculated for a spherical 14 nm diameter Au–MNP decorated with isolated Pheos or with P{sub 16} complexes formed by 16 Pheos. The spectra are analyzed with respect to the molecular orientation at the MNP surface. While all studies on P{sub 16} only account for the Pheo Q{sub y}-transition we also present data on the MNP induced change of the single Pheo Q{sub x}-absorption.

  20. Information storage at the molecular level - The design of a molecular shift register memory

    Science.gov (United States)

    Beratan, David N.; Onuchic, Jose Nelson; Hopfield, J. J.

    1989-01-01

    The control of electron transfer rates is discussed and a molecular shift register memory at the molecular level is described. The memory elements are made up of molecules which can exist in either an oxidized or reduced state and the bits can be shifted between the cells with photoinduced electron transfer reactions. The device integrates designed molecules onto a VLSI substrate. A control structure to modify the flow of information along a shift register is indicated schematically.

  1. Beyond Molecular Wires: Design Molecular Electronic Functions Based on Dipolar Effect.

    Science.gov (United States)

    Lo, Wai-Yip; Zhang, Na; Cai, Zhengxu; Li, Lianwei; Yu, Luping

    2016-09-20

    As the semiconductor companies officially abandoned the pursuit of Moore's law, the limitation of silicone-based semiconductor electronic devices is approaching. Single molecular devices are considered as a potential solution to overcome the physical barriers caused by quantum interferences because the intermolecular interactions are mainly through weak van der Waals force between molecular building blocks. In this bottom-up approach, components are built from atoms up, allowing great control over the molecular properties. Moreover, single molecular devices are powerful tools to understand quantum physics, reaction mechanism, and electron and charge transfer processes in organic semiconductors and molecules. So far, a great deal of effort is focused on understanding charge transport through organic single-molecular wires. However, to control charge transport, molecular diodes, switches, transistors, and memories are crucial. Significant progress in these topics has been achieved in the past years. The introduction and advances of scanning tunneling microscope break-junction (STM-BJ) techniques have led to more detailed characterization of new molecular structures. The modern organic chemistry provides an efficient access to a variety of functional moieties in single molecular device. These moieties have the potential to be incorporated in miniature circuits or incorporated as parts in molecular machines, bioelectronics devices, and bottom-up molecular devices. In this Account, we discuss progress mainly made in our lab in designing and characterizing organic single-molecular electronic components beyond molecular wires and with varied functions. We have synthesized and demonstrated molecular diodes with p-n junction structures through various scanning probe microscopy techniques. The assembly of the molecular diodes was achieved by using Langmuir-Blodgett technique or thiol/gold self-assembly chemistry with orthogonal protecting groups. We have thoroughly

  2. The Journal of Computer- Aided Molecular Design: a bibliometric note

    Science.gov (United States)

    Willett, Peter

    2012-01-01

    Summarizes the articles in, and the citations to, volumes 2-24 of the Journal of Computer- Aided Molecular Design. The citations to the journal come from almost 2000 different sources that span a very wide range of academic subjects, with the most heavily cited articles being descriptions of software systems and of computational methods.

  3. Adhesion of Photon-Driven Molecular Motors to Surfaces via 1,3-Dipolar Cycloadditions : Effect of Interfacial Interactions on Molecular Motion

    NARCIS (Netherlands)

    Carroll, Gregory T.; London, Gabor; Fernández Landaluce, Tatiana; Rudolf, Petra; Feringa, Ben L.

    2011-01-01

    We report the attachment of altitudinal light-driven molecular motors to surfaces using 1,3-dipolar cycloaddition reactions. Molecular motors were designed containing azide or alkyne groups for attachment to alkyne- or azide-modified surfaces. Surface attachment was characterized by UV-vis, IR, XPS,

  4. Structural, electrochemical, and photophysical properties of a molecular shuttle attached to an acid-terminated self-assembled monolayer

    NARCIS (Netherlands)

    Cecchet, F; Rudolf, P; Rapino, S; Margotti, M; Paolucci, F; Baggerman, J; Kay, ER; Wong, JKY; Leigh, DA; Kay, Euan R.; Wong, Jenny K.Y.; Brouwer, A.M.

    2004-01-01

    A benzylic amide macrocycle containing a pyridine moiety (macrocycle 2) and a related benzylic amide macrocycle-based molecular shuttle (naphthalimide rotaxane) with two pyridine moieties on the macrocyclic unit were grafted onto a self-assembled monolayer (SAM) of 11-mercaptoundecanoic acid (11-MUA

  5. Design modification in rotor blade of turbo molecular pump

    Energy Technology Data Exchange (ETDEWEB)

    Iqbal, Munawar, E-mail: muniqbal@yahoo.com [Centre for High Energy Physics, University of the Punjab, Quaid-e-Azam, Campus, Lahore 54590 (Pakistan); Wasy, Abdul [Department of Mechanical Engineering, University of Engineering and Technology, Taxila 47050 (Pakistan); Batani, Dimitri [Centre Lasers Intenses et Applications, Universite Bordeaux 1, Liberation, 33405 Talence cedex (France); Rashid, Haris [Centre for High Energy Physics, University of the Punjab, Quaid-e-Azam, Campus, Lahore 54590 (Pakistan); Lodhi, M.A.K. [Department of Physics, Texas Tech University, Lubbock Texas, 79409 (United States)

    2012-06-21

    Performance of a Turbo Molecular Pump (TMP) is strongly related to the frequency of the rotor. As rpm increases deflection in the rotor blades starts to occur. Therefore, quality of material and blade design has been modified in order to obtain stable performance at higher speed. To reduce the deformation, stiffer material and change in blade design have been calculated. Significant improvement has been achieved in modeling the blade design using CATIA software. The analysis has been performed by ANSYS workbench. It is shown that the modification in the blade design of TMP rotor has reduced the structural deformation up to 66 percent of the deformation produced in the original blade design under the same conditions. Modified design achieved additional 23 percent rpm which increased TMP's efficiency.

  6. Design modification in rotor blade of turbo molecular pump

    Science.gov (United States)

    Iqbal, Munawar; Wasy, Abdul; Batani, Dimitri; Rashid, Haris; Lodhi, M. A. K.

    2012-06-01

    Performance of a Turbo Molecular Pump (TMP) is strongly related to the frequency of the rotor. As rpm increases deflection in the rotor blades starts to occur. Therefore, quality of material and blade design has been modified in order to obtain stable performance at higher speed. To reduce the deformation, stiffer material and change in blade design have been calculated. Significant improvement has been achieved in modeling the blade design using CATIA software. The analysis has been performed by ANSYS workbench. It is shown that the modification in the blade design of TMP rotor has reduced the structural deformation up to 66 percent of the deformation produced in the original blade design under the same conditions. Modified design achieved additional 23 percent rpm which increased TMP's efficiency.

  7. Versatile design of biohybrid light-harvesting architectures to tune location, density, and spectral coverage of attached synthetic chromophores for enhanced energy capture.

    Science.gov (United States)

    Harris, Michelle A; Jiang, Jianbing; Niedzwiedzki, Dariusz M; Jiao, Jieying; Taniguchi, Masahiko; Kirmaier, Christine; Loach, Paul A; Bocian, David F; Lindsey, Jonathan S; Holten, Dewey; Parkes-Loach, Pamela S

    2014-07-01

    Biohybrid antennas built upon chromophore-polypeptide conjugates show promise for the design of efficient light-capturing modules for specific purposes. Three new designs, each of which employs analogs of the β-polypeptide from Rhodobacter sphaeroides, have been investigated. In the first design, amino acids at seven different positions on the polypeptide were individually substituted with cysteine, to which a synthetic chromophore (bacteriochlorin or Oregon Green) was covalently attached. The polypeptide positions are at -2, -6, -10, -14, -17, -21, and -34 relative to the 0-position of the histidine that coordinates bacteriochlorophyll a (BChl a). All chromophore-polypeptides readily formed LH1-type complexes upon combination with the α-polypeptide and BChl a. Efficient energy transfer occurs from the attached chromophore to the circular array of 875 nm absorbing BChl a molecules (denoted B875). In the second design, use of two attachment sites (positions -10 and -21) on the polypeptide affords (1) double the density of chromophores per polypeptide and (2) a highly efficient energy-transfer relay from the chromophore at -21 to that at -10 and on to B875. In the third design, three spectrally distinct bacteriochlorin-polypeptides were prepared (each attached to cysteine at the -14 position) and combined in an ~1:1:1 mixture to form a heterogeneous mixture of LH1-type complexes with increased solar coverage and nearly quantitative energy transfer from each bacteriochlorin to B875. Collectively, the results illustrate the great latitude of the biohybrid approach for the design of diverse light-harvesting systems.

  8. Micro-/nanostructured multicomponent molecular materials: design, assembly, and functionality.

    Science.gov (United States)

    Yan, Dongpeng

    2015-03-23

    Molecule-based micro-/nanomaterials have attracted considerable attention because their properties can vary greatly from the corresponding macro-sized bulk systems. Recently, the construction of multicomponent molecular solids based on crystal engineering principles has emerged as a promising alternative way to develop micro-/nanomaterials. Unlike single-component materials, the resulting multicomponent systems offer the advantages of tunable composition, and adjustable molecular arrangement, and intermolecular interactions within their solid states. The study of these materials also supplies insight into how the crystal structure, molecular components, and micro-/nanoscale effects can influence the performance of molecular materials. In this review, we describe recent advances and current directions in the assembly and applications of crystalline multicomponent micro-/nanostructures. Firstly, the design strategies for multicomponent systems based on molecular recognition and crystal engineering principles are introduced. Attention is then focused on the methods of fabrication of low-dimensional multicomponent micro-/nanostructures. Their new applications are also outlined. Finally, we briefly discuss perspectives for the further development of these molecular crystalline micro-/nanomaterials.

  9. Molecular design of an epoxy for cryogenic temperatures

    Science.gov (United States)

    Sawa, Fumio; Nishijima, Shigehiro; Okada, Toichi

    The mechanical and thermal properties of several epoxy resins were measured to obtain guidelines for the molecular design of an epoxy resin for cryogenic temperatures. Two types of epoxy resin with different numbers of epoxy groups were mixed (with different mixing ratios) and cured. Fracture toughness, flexural strength and thermal contraction of the hybrid epoxy resins were measured down to cryogenic temperatures. The results suggest that epoxies with larger molecular weights between crosslinkings relaxed stress at the crack tip, even at cryogenic temperatures. Intermolecular forces and stress relaxation at the crack tip were found to be important for high fracture toughness.

  10. Molecular docking and structure-based drug design strategies.

    Science.gov (United States)

    Ferreira, Leonardo G; Dos Santos, Ricardo N; Oliva, Glaucius; Andricopulo, Adriano D

    2015-07-22

    Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  11. Virtual Screening and Molecular Design Based on Hierarchical Qsar Technology

    Science.gov (United States)

    Kuz'min, Victor E.; Artemenko, A. G.; Muratov, Eugene N.; Polischuk, P. G.; Ognichenko, L. N.; Liahovsky, A. V.; Hromov, A. I.; Varlamova, E. V.

    This chapter is devoted to the hierarchical QSAR technology (HiT QSAR) based on simplex representation of molecular structure (SiRMS) and its application to different QSAR/QSPR tasks. The essence of this technology is a sequential solution (with the use of the information obtained on the previous steps) of the QSAR paradigm by a series of enhanced models based on molecular structure description (in a specific order from 1D to 4D). Actually, it's a system of permanently improved solutions. Different approaches for domain applicability estimation are implemented in HiT QSAR. In the SiRMS approach every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality, and symmetry). The level of simplex descriptors detailed increases consecutively from the 1D to 4D representation of the molecular structure. The advantages of the approach presented are an ability to solve QSAR/QSPR tasks for mixtures of compounds, the absence of the "molecular alignment" problem, consideration of different physical-chemical properties of atoms (e.g., charge, lipophilicity), and the high adequacy and good interpretability of obtained models and clear ways for molecular design. The efficiency of HiT QSAR was demonstrated by its comparison with the most popular modern QSAR approaches on two representative examination sets. The examples of successful application of the HiT QSAR for various QSAR/QSPR investigations on the different levels (1D-4D) of the molecular structure description are also highlighted. The reliability of developed QSAR models as the predictive virtual screening tools and their ability to serve as the basis of directed drug design was validated by subsequent synthetic, biological, etc. experiments. The HiT QSAR is realized as the suite of computer programs termed the "HiT QSAR" software that so includes powerful statistical capabilities and a number of useful utilities.

  12. Insights from molecular dynamics simulations for computational protein design.

    Science.gov (United States)

    Childers, Matthew Carter; Daggett, Valerie

    2017-02-01

    A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.

  13. Remedial action plan and site design for stabilization of the inactive uranium processing site at Naturita, Colorado. Appendix B of Attachment 3: Groundwater hydrology report, Attachment 4: Water resources protection strategy, Final

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    Attachment 3 Groundwater Hydrology Report describes the hydrogeology, water quality, and water resources at the processing site and Dry Flats disposal site. The Hydrological Services calculations contained in Appendix A of Attachment 3, are presented in a separate report. Attachment 4 Water Resources Protection Strategy describes how the remedial action will be in compliance with the proposed EPA groundwater standards.

  14. Molecular Understanding and Structural-Based Design of Polyacrylamides and Polyacrylates as Antifouling Materials.

    Science.gov (United States)

    Chen, Hong; Zhao, Chao; Zhang, Mingzhen; Chen, Qiang; Ma, Jie; Zheng, Jie

    2016-04-12

    Design and synthesis of highly bioinert and biocompatible antifouling materials are crucial for a broad range of biomedical and engineering applications. Among antifouling materials, polyacrylamides and polyacrylates have proved so promising because of cheap raw materials, ease of synthesis and applicability, and abundant functional groups. The strong surface hydration and the high surface packing density of polyacrylamides and polyacrylates are considered to be the key contributors to their antifouling property. In this article, we review our studies on the design and synthesis of a series of polyacrylamides and polyacrylates with different molecular structures. These polymers can be fabricated into different architectural forms (brushes, nanoparticles, nanogels, and hydrogels), all of which are highly resistant to the attachment of proteins, cells, and bacteria. We find that small structural changes in the polymers can lead to large enhancement in surface hydration and antifouling performance, both showing a positive correlation. This reveals a general design rule for effective antifouling materials. Furthermore, polyacrylamides and polyacrylates are readily functionalized with other bioactive compounds to achieve different new multifunctionalities.

  15. Optimally designed nanolayered metal-dielectric particles as probes for massively multiplexed and ultrasensitive molecular assays.

    Science.gov (United States)

    Kodali, Anil K; Llora, Xavier; Bhargava, Rohit

    2010-08-03

    An outstanding challenge in biomedical sciences is to devise a palette of molecular probes that can enable simultaneous and quantitative imaging of tens to hundreds of species down to ultralow concentrations. Addressing this need using surface-enhanced Raman scattering-based probes is potentially possible. Here, we theorize a rational design and optimization strategy to obtain reproducible probes using nanospheres with alternating metal and reporter-filled dielectric layers. The isolation of reporter molecules from metal surfaces suppresses chemical enhancement, and consequently signal enhancements are determined by electromagnetic effects alone. This strategy synergistically couples interstitial surface plasmons and permits the use of almost any molecule as a reporter by eliminating the need for surface attachment. Genetic algorithms are employed to optimize the layer dimensions to provide controllable enhancements exceeding 11 orders of magnitude and of single molecule sensitivity for nonresonant and resonant reporters, respectively. The strategy also provides several other opportunities, including a facile route to tuning the response of these structures to be spectrally flat and localization of the enhancement within a specific volume inside or outside the probe. The spectrally uniform enhancement for multiple excitation wavelengths and for different shifts enables generalized probes, whereas enhancement tuning permits a large dynamic range by suppression of enhancements from outside the probe. Combined, these theoretical calculations open the door for a set of reproducible and robust probes with controlled sensitivity for molecular sensing over a concentration range of over 20 orders of magnitude.

  16. MOLECULAR DESIGN OF NEW KINDS OF AUXETIC POLYMERS AND NETWORKS

    Institute of Scientific and Technical Information of China (English)

    Hong-mei Wu; Gao-yuan Wei

    2004-01-01

    Three new kinds of molecular networks are designed and predicted to exhibit negative Poisson ratios. Molecular mechanics calculations on these networks show that the magnitude of Poisson ratios depends on the relative flexibility of beam and arm structures. Several new kinds of auxetic polymers, whose successful synthesis should be easier than that of the corresponding auxetic networks, are then proposed. It is found that the kabob-like polymers with auxegens lying vertically on the main chain can acquire auxeticity while those with auxegens lying horizontally on the main chain cannot. Besides, a half kabob-like or pseudo-ladder polymer with auxegens linked at the intersection of the beam and the arm does show auxeticity when adopting constrictive conformers. It is, however, worthwhile noting that the origins of auxeticity still await and strongly deserve further experimental and theoretical investigations.

  17. Bar overdentures utilizing the Locator attachment.

    Science.gov (United States)

    Schneider, A L; Kurtzman, G M

    2001-01-01

    Implant-retained overdentures are a restorative option for both the fully and partially edentulous arches. A new attachment, the Locator, which features a reduced interarch requirement and the advantage of built-in guide planes providing precise insertion, is described. The Locator is an advancement in attachment technology, with an improved design combined from the best features of a ball attachment, an ERA attachment, and a cap attachment.

  18. A comparative molecular force spectroscopy study of homophilic JAM-A interactions and JAM-A interactions with reovirus attachment protein sigma1.

    Science.gov (United States)

    Vedula, Sri Ram Krishna; Lim, Tong Seng; Kirchner, Eva; Guglielmi, Kristen M; Dermody, Terence S; Stehle, Thilo; Hunziker, Walter; Lim, Chwee Teck

    2008-01-01

    JAM-A belongs to a family of immunoglobulin-like proteins called junctional adhesion molecules (JAMs) that localize at epithelial and endothelial intercellular tight junctions. JAM-A is also expressed on dendritic cells, neutrophils, and platelets. Homophilic JAM-A interactions play an important role in regulating paracellular permeability and leukocyte transmigration across epithelial monolayers and endothelial cell junctions, respectively. In addition, JAM-A is a receptor for the reovirus attachment protein, sigma1. In this study, we used single molecular force spectroscopy to compare the kinetics of JAM-A interactions with itself and sigma1. A chimeric murine JAM-A/Fc fusion protein and the purified sigma1 head domain were used to probe murine L929 cells, which express JAM-A and are susceptible to reovirus infection. The bond half-life (t(1/2)) of homophilic JAM-A interactions was found to be shorter (k(off)(o) = 0.688 +/- 0.349 s(-1)) than that of sigma1/JAM-A interactions (k(off)(o) = 0.067 +/- 0.041 s(-1)). These results are in accordance with the physiological functions of JAM-A and sigma1. A short bond lifetime imparts a highly dynamic nature to homophilic JAM-A interactions for regulating tight junction permeability while stable interactions between sigma1 and JAM-A likely anchor the virus to the cell surface and facilitate viral entry.

  19. Modeling the role of electron attachment rates on column density ratios for CnH-/CnH (n=4,6,8) in dense molecular clouds

    CERN Document Server

    Gianturco, F A; Wester, R

    2016-01-01

    (abridged) The fairly recent detection of a variety of anions in the Interstellar Molecular Clouds have underlined the importance of realistically modeling the processes governing their abundance. To this aim, our earlier calculations for the radiative electron attachment (REA) rates for C4H-, C6H-, and C8H- are employed to generate the corresponding column density ratios of anion/neutral (A/N) relative abundances. The latter are then compared with those obtained from observational measurements. The calculations involved the time-dependent solutions of a large network of chemical processes over an extended time interval and included a series of runs in which the values of REA rates were repeatedly scaled. Macroscopic parameters for the clouds' modeling were also varied to cover a broad range of physical environments. It was found that, within the range and quality of the processes included in the present network,and selected from state-of-the-art astrophysical databases, the REA values required to match the o...

  20. Comparing Simulated Emission from Molecular Clouds Using Experimental Design

    CERN Document Server

    Yeremi, Miayan; Offner, Stella; Loeppky, Jason; Rosolowsky, Erik

    2014-01-01

    We propose a new approach to comparing simulated observations that enables us to determine the significance of the underlying physical effects. We utilize the methodology of experimental design, a subfield of statistical analysis, to establish a framework for comparing simulated position-position-velocity data cubes to each other. We propose three similarity metrics based on methods described in the literature: principal component analysis, the spectral correlation function, and the Cramer multi-variate two sample similarity statistic. Using these metrics, we intercompare a suite of mock observational data of molecular clouds generated from magnetohydrodynamic simulations with varying physical conditions. Using this framework, we show that all three metrics are sensitive to changing Mach number and temperature in the simulation sets, but cannot detect changes in magnetic field strength and initial velocity spectrum. We highlight the shortcomings of one-factor-at-a-time designs commonly used in astrophysics an...

  1. Molecular design of new chromophores for high performance poled polymers

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Based on the principles of molecular engineering, a series of new chromophores with high second-or der nonlinear optical(NLO)activities have been designed for achieving a trade-off of the nonlinearity-transparency-ther mal stability. The NLO properties of these chromophores have been investigated theoretically by employing the AMI/Fi nite Field approach. It is found that the calculated μβ0 values of some designed chromophores can reach the magnitude of 10-45 esu, and the highest decomposition temperature Td can be as high as 377℃, the highest glass transition tem perature Ts of their donor-embedded addition-type polyimides can be as high as 324℃.

  2. Molecular Docking and Structure-Based Drug Design Strategies

    Directory of Open Access Journals (Sweden)

    Leonardo G. Ferreira

    2015-07-01

    Full Text Available Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  3. Design, validation, and absolute sensitivity of a novel test for the molecular detection of avian pneumovirus.

    Science.gov (United States)

    Cecchinato, Mattia; Catelli, Elena; Savage, Carol E; Jones, Richard C; Naylor, Clive J

    2004-11-01

    This study describes attempts to increase and measure sensitivity of molecular tests to detect avian pneumovirus (APV). Polymerase chain reaction (PCR) diagnostic tests were designed for the detection of nucleic acid from an A-type APV genome. The objective was selection of PCR oligonucleotide combinations, which would provide the greatest test sensitivity and thereby enable optimal detection when used for later testing of field materials. Relative and absolute test sensitivities could be determined because of laboratory access to known quantities of purified full-length DNA copies of APV genome derived from the same A-type virus. Four new nested PCR tests were designed in the fusion (F) protein (2 tests), small hydrophobic (SH) protein (1 test), and nucleocapsid (N) protein (1 test) genes and compared with an established test in the attachment (G) protein gene. Known amounts of full-length APV genome were serially diluted 10-fold, and these dilutions were used as templates for the different tests. Sensitivities were found to differ between the tests, the most sensitive being the established G test, which proved able to detect 6,000 copies of the G gene. The G test contained predominantly pyrimidine residues at its 3' termini, and because of this, oligonucleotides for the most sensitive F test were modified to incorporate the same residue types at their 3' termini. This was found to increase sensitivity, so that after full 3' pyrimidine substitutions, the F test became able to detect 600 copies of the F gene.

  4. Design and function of molecular and bioelectronics devices.

    Science.gov (United States)

    Krstic, Predrag; Forzani, Erica; Tao, Nongjian; Korkin, Anatoli

    2007-10-24

    Further rapid progress of electronics, in particular the increase of computer power and breakthroughs in sensor technology for industrial, medical diagnostics and environmental applications, strongly depends on the scaling of electronic devices, ultimately to the size of molecules. Design of controllable molecular-scale devices may resolve the problem of energy dissipation at the nanoscale and take advantage of molecular self-assembly in the so-called bottom-up approach. This special issue of Nanotechnology is devoted to a better understanding of the function and design of molecular-scale devices that are relevant to future electronics and sensor technology. Papers contained in this special issue are selected from the symposium Nano and Giga Challenges in Electronics and Photonics: From Atoms to Materials to Devices to System Architecture (12-16 March, 2007, Phoenix, Arizona, USA), as well as from original and novel scientific contributions of invited world-renown researchers. It addresses both theoretical and experimental achievements in the fields of molecular and bioelectronics, chemical and biosensors at the molecular level, including carbon nanotubes, novel nanostructures, as well as related research areas and industrial applications. The conference series Nano and Giga Challenges in Electronics and Photonics was launched as a truly interdisciplinary forum to bridge scientists and engineers to work across boundaries in the design of future information technologies, from atoms to materials to devices to system architecture. Following the first two successful meetings in Moscow, Russia (NGCM2002) and Krakow, Poland (NGCM2004), the third Nano and Giga Forum (NGC2007) was held in 2007 hosted by Arizona State University. Besides this special issue of Nanotechnology, two other collections (in the journal Solid State Electronics and the tutorial book in the series Nanostructure Science and Technology Springer) have published additional selected and invited papers

  5. EDITORIAL: Design and function of molecular and bioelectronics devices

    Science.gov (United States)

    Krstic, Predrag; Forzani, Erica; Tao, Nongjian; Korkin, Anatoli

    2007-10-01

    Further rapid progress of electronics, in particular the increase of computer power and breakthroughs in sensor technology for industrial, medical diagnostics and environmental applications, strongly depends on the scaling of electronic devices, ultimately to the size of molecules. Design of controllable molecular-scale devices may resolve the problem of energy dissipation at the nanoscale and take advantage of molecular self-assembly in the so-called bottom-up approach. This special issue of Nanotechnology is devoted to a better understanding of the function and design of molecular-scale devices that are relevant to future electronics and sensor technology. Papers contained in this special issue are selected from the symposium Nano and Giga Challenges in Electronics and Photonics: From Atoms to Materials to Devices to System Architecture (12-16 March, 2007, Phoenix, Arizona, USA), as well as from original and novel scientific contributions of invited world-renown researchers. It addresses both theoretical and experimental achievements in the fields of molecular and bioelectronics, chemical and biosensors at the molecular level, including carbon nanotubes, novel nanostructures, as well as related research areas and industrial applications. The conference series Nano and Giga Challenges in Electronics and Photonics was launched as a truly interdisciplinary forum to bridge scientists and engineers to work across boundaries in the design of future information technologies, from atoms to materials to devices to system architecture. Following the first two successful meetings in Moscow, Russia (NGCM2002) and Krakow, Poland (NGCM2004), the third Nano and Giga Forum (NGC2007) was held in 2007 hosted by Arizona State University. Besides this special issue of Nanotechnology, two other collections (in the journal Solid State Electronics and the tutorial book in the series Nanostructure Science and Technology Springer) have published additional selected and invited papers

  6. Molecular Design of Branched and Binary Molecules at Ordered Interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Genson, Kirsten Larson [Iowa State Univ., Ames, IA (United States)

    2005-01-01

    This study examined five different branched molecular architectures to discern the effect of design on the ability of molecules to form ordered structures at interfaces. Photochromic monodendrons formed kinked packing structures at the air-water interface due to the cross-sectional area mismatch created by varying number of alkyl tails and the hydrophilic polar head group. The lower generations formed orthorhombic unit cell with long range ordering despite the alkyl tails tilted to a large degree. Favorable interactions between liquid crystalline terminal groups and the underlying substrate were observed to compel a flexible carbosilane dendrimer core to form a compressed elliptical conformation which packed stagger within lamellae domains with limited short range ordering. A twelve arm binary star polymer was observed to form two dimensional micelles at the air-water interface attributed to the higher polystyrene block composition. Linear rod-coil molecules formed a multitude of packing structures at the air-water interface due to the varying composition. Tree-like rod-coil molecules demonstrated the ability to form one-dimensional structures at the air-water interface and at the air-solvent interface caused by the preferential ordering of the rigid rod cores. The role of molecular architecture and composition was examined and the influence chemically competing fragments was shown to exert on the packing structure. The amphiphilic balance of the different molecular series exhibited control on the ordering behavior at the air-water interface and within bulk structures. The shell nature and tail type was determined to dictate the preferential ordering structure and molecular reorganization at interfaces with the core nature effect secondary.

  7. Advances in molecular design and synthesis of regioregular polythiophenes.

    Science.gov (United States)

    Osaka, Itaru; McCullough, Richard D

    2008-09-01

    Regioregular poly(3-alkylthiophene)s (rrP3ATs) are an important class of pi-conjugated polymers that can be used in plastic electronic devices such as solar cells and field-effect transistors. rrP3ATs can be ordered in three dimensions: conformational ordering along the backbone, pi-stacking of flat polymer chains, and lamellar stacking between chains. All of these features lead to the excellent electrical properties of these materials. Creative molecular design and advanced synthesis are critical in controlling the properties of the materials as well as their device performance. This Account reports the advances in molecular design of new functional polythiophenes as well as the associated polymerization methods. Many functionalized regioregular polythiophenes have been designed and synthesized and show fascinating properties such as high conductivity, mobility, chemosensitivity, liquid crystallinity, or chirality. The methods for the synthesis of rrP3ATs are also applicable to other functional side chains. Di- and triblock copolymers consisting of rrP3AT and polyacrylate or polystyrene have also been successfully synthesized, which can facilitate the assembly of the polythiophene segments. The synthesis of rrP3ATs has evolved into a simple and economical system in which the synthesis can be carried out quickly at room temperature and is thus suitable for large-scale manufacturing. Intensive study has revealed that the regioregular polymerization of 3-alkylthiophenes proceeds by a chain-growth mechanism and can be made into a living system. This feature enables precise control of the molecular weight and facile end-group functionalization of the polymer chains, leading to tailor-made regioregular polythiophenes for specific applications. In addition, researchers have recently designed and synthesized regiosymmetric polythiophenesthese are regioregular but not coupled in a head-to-tail fashionby various methods. These reports indicate that these regiosymmetric

  8. From molecular design and materials construction to organic nanophotonic devices.

    Science.gov (United States)

    Zhang, Chuang; Yan, Yongli; Zhao, Yong Sheng; Yao, Jiannian

    2014-12-16

    CONSPECTUS: Nanophotonics has recently received broad research interest, since it may provide an alternative opportunity to overcome the fundamental limitations in electronic circuits. Diverse optical materials down to the wavelength scale are required to develop nanophotonic devices, including functional components for light emission, transmission, and detection. During the past decade, the chemists have made their own contributions to this interdisciplinary field, especially from the controlled fabrication of nanophotonic molecules and materials. In this context, organic micro- or nanocrystals have been developed as a very promising kind of building block in the construction of novel units for integrated nanophotonics, mainly due to the great versatility in organic molecular structures and their flexibility for the subsequent processing. Following the pioneering works on organic nanolasers and optical waveguides, the organic nanophotonic materials and devices have attracted increasing interest and developed rapidly during the past few years. In this Account, we review our research on the photonic performance of molecular micro- or nanostructures and the latest breakthroughs toward organic nanophotonic devices. Overall, the versatile features of organic materials are highlighted, because they brings tunable optical properties based on molecular design, size-dependent light confinement in low-dimensional structures, and various device geometries for nanophotonic integration. The molecular diversity enables abundant optical transitions in conjugated π-electron systems, and thus brings specific photonic functions into molecular aggregates. The morphology of these micro- or nanostructures can be further controlled based on the weak intermolecular interactions during molecular assembly process, making the aggregates show photon confinement or light guiding properties as nanophotonic materials. By adoption of some active processes in the composite of two or more

  9. A computer-aided molecular design framework for crystallization solvent design

    DEFF Research Database (Denmark)

    Karunanithi, Arunprakash T.; Achenie, Luke E.K.; Gani, Rafiqul

    2006-01-01

    One of the key decisions in designing solution crystallization processes is the selection of solvents. In this paper, we present a computer-aided molecular design (CAMD) framework for the design and selection of solvents and/or anti-solvents for solution crystallization. The CAMD problem......, property requirements such as solubility, crystal morphology, flashpoint, toxicity, viscosity, normal boiling and melting point are posed as constraints. All the properties are estimated using group contribution methods. The MINLP model is then solved using a decomposition approach to obtain optimal...... solvent molecules. Solvent design and selection for two types of solution crystallization processes namely cooling crystallization and drowning out crystallization are presented. In the first case study, the design of single compound solvent for crystallization of ibuprofen, which is an important...

  10. Three decades of structure- and property-based molecular design.

    Science.gov (United States)

    Müller, Klaus

    2014-01-01

    Roche has pioneered structure- and property-based molecular design to drug discovery. While this is an ongoing development, the past three decades feature key events that have revolutionized the way drug discovery is conducted in Big Pharma industry. It has been a great privilege to have been involved in this transformation process, to have been able to collaborate with, direct, guide, or simply encourage outstanding experts in various disciplines to build and further develop what has become a major pillar of modern small-molecule drug discovery. This article is an account of major events that took place since the early decision of Roche to implement computer-assisted molecular modeling 32 years ago and is devoted to the key players involved. It highlights the internal build-up of structural biology, with protein X-ray structure determination at its core, and the early setup of bioinformatics. It describes the strategic shift to large compound libraries and high-throughput screening with the development of novel compound storage and ultra-high-throughput screening facilities, as well as the strategic return to focused screening of small motif-based compound libraries. These developments were accompanied by the rise of miniaturized parallel compound property analytics which resulted in a major paradigm shift in medicinal chemistry from linear to multi-dimensional lead optimization. The rapid growth of huge collections of property data stimulated the development of various novel data mining concepts with 'matched molecular pair' analysis and novel variants thereof playing crucial roles. As compound properties got more prominent in molecular design, exploration of specific structural motifs for property modulation became a research activity complementary to target-oriented medicinal chemistry. The exploration of oxetane is given as an example. For the sake of brevity, this account cannot detail all further developments that have taken place in each individual area of

  11. Design and Performance of a Compact Li+ Ion Attachment Mass Spectrometry System with an Atmospheric Sampling Device

    Science.gov (United States)

    Takahashi, Seiji; Nakamura, Megumi; Fujii, Toshihiro

    2012-03-01

    This report describes the development of a compact ion attachment mass spectrometry system. A single turbomolecular pump was employed to fill the basic requirements for vacuum conditions simply and cost-effectively, without the need for a differential pumping stage. A Li+ ion source was placed in the first of two vacuum chambers; a 0.4 mm aperture allowed the product ions to enter the second chamber for mass analysis. With the present system, any chemical species, including radical intermediates, can be detected at atmospheric pressure in real-time. The minimum detectable amount (at S/ N = 3) of toluene was around 1.3 × 10-12 g/s with a linearity greater than 104. For illustrative purposes, we tested the system on laboratory air and on aroma compounds in the headspace of the Yuzu plant, Citrus junos.

  12. Comparing simulated emission from molecular clouds using experimental design

    Energy Technology Data Exchange (ETDEWEB)

    Yeremi, Miayan; Flynn, Mallory; Loeppky, Jason; Rosolowsky, Erik [University of British Columbia, Okanagan Campus, Departments of Physics and Statistics, 3333 University Way, Kelowna BC V1V 1V7 (Canada); Offner, Stella [Yale University Astronomy Department, 260 Whitney Avenue, New Haven, CT 06511 (United States)

    2014-03-10

    We propose a new approach to comparing simulated observations that enables us to determine the significance of the underlying physical effects. We utilize the methodology of experimental design, a subfield of statistical analysis, to establish a framework for comparing simulated position-position-velocity data cubes to each other. We propose three similarity metrics based on methods described in the literature: principal component analysis, the spectral correlation function, and the Cramer multi-variate two-sample similarity statistic. Using these metrics, we intercompare a suite of mock observational data of molecular clouds generated from magnetohydrodynamic simulations with varying physical conditions. Using this framework, we show that all three metrics are sensitive to changing Mach number and temperature in the simulation sets, but cannot detect changes in magnetic field strength and initial velocity spectrum. We highlight the shortcomings of one-factor-at-a-time designs commonly used in astrophysics and propose fractional factorial designs as a means to rigorously examine the effects of changing physical properties while minimizing the investment of computational resources.

  13. Design and performance simulation of a molecular Doppler wind lidar

    Institute of Scientific and Technical Information of China (English)

    Fahua Shen; Hyunki Cha; Jihui Dong; Dukhyeon Kim; Dongsong Sun; Sung Ok Kwon

    2009-01-01

    A mobile molecular Doppler wind lidar at an eye-safe wavelength of 355 nm based on double-edge technique is being built in Hefei (China) for wind measurement from 10-to 40-km altitude. The structure of this lidar system is described. A triple Fabry-Perot etalon is employed as a frequency discriminator whose parameters are optimized. The receiver system is designed to achieve compactness and stability by putting in a standard 19-inch socket bench. Simulation results show that within the wind speed dynamic range of ±100 m/s, the horizontal wind errors due to noise are less than 1 m/s below 20-km altitude for 100-m vertical resolution, and less than 5.5 m/s from 20 km up to 40 km for 500-m vertical resolution with 400-mJ laser energy, 30-min temporal resolution, and a 45-cm aperture telescope.

  14. Three decades of structure- and property-based molecular design

    DEFF Research Database (Denmark)

    Müller, Klaus

    2014-01-01

    of bioinformatics. It describes the strategic shift to large compound libraries and high-throughput screening with the development of novel compound storage and ultra-high-throughput screening facilities, as well as the strategic return to focused screening of small motif-based compound libraries......Roche has pioneered structure- and property-based molecular design to drug discovery. While this is an ongoing development, the past three decades feature key events that have revolutionized the way drug discovery is conducted in Big Pharma industry. It has been a great privilege to have been...... involved in this transformation process, to have been able to collaborate with, direct, guide, or simply encourage outstanding experts in various disciplines to build and further develop what has become a major pillar of modern small-molecule drug discovery. This article is an account of major events...

  15. 30 CFR 77.1436 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 77.1436 Section 77.1436... Hoisting Wire Ropes § 77.1436 Drum end attachment. (a) For drum end attachment, wire rope shall be attached... anchor bolts, clamps, or wedges, provided that the attachment is a design feature of the hoist...

  16. Bayesian molecular design with a chemical language model.

    Science.gov (United States)

    Ikebata, Hisaki; Hongo, Kenta; Isomura, Tetsu; Maezono, Ryo; Yoshida, Ryo

    2017-03-09

    The aim of computational molecular design is the identification of promising hypothetical molecules with a predefined set of desired properties. We address the issue of accelerating the material discovery with state-of-the-art machine learning techniques. The method involves two different types of prediction; the forward and backward predictions. The objective of the forward prediction is to create a set of machine learning models on various properties of a given molecule. Inverting the trained forward models through Bayes' law, we derive a posterior distribution for the backward prediction, which is conditioned by a desired property requirement. Exploring high-probability regions of the posterior with a sequential Monte Carlo technique, molecules that exhibit the desired properties can computationally be created. One major difficulty in the computational creation of molecules is the exclusion of the occurrence of chemically unfavorable structures. To circumvent this issue, we derive a chemical language model that acquires commonly occurring patterns of chemical fragments through natural language processing of ASCII strings of existing compounds, which follow the SMILES chemical language notation. In the backward prediction, the trained language model is used to refine chemical strings such that the properties of the resulting structures fall within the desired property region while chemically unfavorable structures are successfully removed. The present method is demonstrated through the design of small organic molecules with the property requirements on HOMO-LUMO gap and internal energy. The R package iqspr is available at the CRAN repository.

  17. Intelligent Design of Nano-Scale Molecular Imaging Agents

    Directory of Open Access Journals (Sweden)

    Takeaki Ozawa

    2012-12-01

    Full Text Available Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs, biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

  18. Design of ferroelectric organic molecular crystals with ultrahigh polarization.

    Science.gov (United States)

    Chen, Shuang; Zeng, Xiao Cheng

    2014-04-30

    Inspired by recent successful synthesis of room-temperature ferroelectric supramolecular charge-transfer complexes, i.e., tetrathiafulvalene (TTF)- and pyromellitic diimide (PMDI)-based crystals (Tayi et al. Nature 2012, 488, 485-489), three new ferroelectric two-component organic molecular crystals are designed based on the TTF and PMDI motifs and an extensive polymorph search. To achieve energetically favorable packing structures for the crystals, a newly developed computational approach that combines polymorph predictor with density functional theory (DFT) geometry optimization is employed. Tens of thousands of packing structures for the TTF- and PMDI-based crystals are first generated based on the limited number of asymmetric units in a unit cell as well as limited common symmetry groups for organocarbon crystals. Subsequent filtering of these packing structures by comparing with the reference structures yields dozens of promising crystal structures. Further DFT optimizations allow us to identify several highly stable packing structures that possess the space group of P2₁ as well as high to ultrahigh spontaneous polarizations (23-127 μC/cm(2)) along the crystallographic b axis. These values are either comparable to or much higher than the computed value (25 μC/cm(2)) or measured value (55 μC/cm(2)) for the state-of-the-art organic supramolecular systems. The high polarization arises from the ionic displacement. We further construct surface models to derive the electric-field-switched low-symmetry structures of new TTF- and PMDI-based crystals. By comparing the high-symmetry and low-symmetry crystal structures, we find that the ferroelectric polarization of the crystals is very sensitive to atomic positions, and a small molecular displacement may result in relatively high polarizations along the a and c axes, polarity reversal, and/or electronic contribution to polarization. If these newly designed TTF- and PMDI-based crystals with high polarizations are

  19. Design of optimal collimation for dedicated molecular breast imaging systems

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, Amanda L.; Hruska, Carrie B.; O' Connor, Michael K. [Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, Minnesota 55905 (United States)

    2009-03-15

    Molecular breast imaging (MBI) is a functional imaging technique that uses specialized small field-of-view gamma cameras to detect the preferential uptake of a radiotracer in breast lesions. MBI has potential to be a useful adjunct method to screening mammography for the detection of occult breast cancer. However, a current limitation of MBI is the high radiation dose (a factor of 7-10 times that of screening mammography) associated with current technology. The purpose of this study was to optimize the gamma camera collimation with the aim of improving sensitivity while retaining adequate resolution for the detection of sub-10-mm lesions. Square-hole collimators with holes matched to the pixilated cadmium zinc telluride detector elements of the MBI system were designed. Data from MBI patient studies and parameters of existing dual-head MBI systems were used to guide the range of desired collimator resolutions, source-to-collimator distances, pixel sizes, and collimator materials that were examined. General equations describing collimator performance for a conventional gamma camera were used in the design process along with several important adjustments to account for the specialized imaging geometry of the MBI system. Both theoretical calculations and a Monte Carlo model were used to measure the geometric efficiency (or sensitivity) and resolution of each designed collimator. Results showed that through optimal collimation, collimator sensitivity could be improved by factors of 1.5-3.2, while maintaining a collimator resolution of either {<=}5 or {<=}7.5 mm at a distance of 3 cm from the collimator face. These gains in collimator sensitivity permit an inversely proportional drop in the required dose to perform MBI.

  20. Mechanical Deformation of Sintered Porous Ag Die Attach at High Temperature and Its Size Effect for Wide-Bandgap Power Device Design

    Science.gov (United States)

    Chen, Chuantong; Nagao, Shijo; Zhang, Hao; Jiu, Jinting; Sugahara, Tohru; Suganuma, Katsuaki; Iwashige, Tomohito; Sugiura, Kazuhiko; Tsuruta, Kazuhiro

    2016-12-01

    The mechanical properties of sintered Ag paste with microporous structure have been investigated by tensile and shear tests, focusing on the temperature-dependent plastic deformation at various temperatures from 25°C to 300°C, corresponding to the target operating temperature range of emerging wide-bandgap semiconductor devices. Specimens were prepared by sintering hybrid Ag paste consisting of microflake and submicron spherical Ag particles, simulating a typical bonding process for power semiconductor die attach. Mechanical tests revealed that the unique microstructure caused a brittle-to-ductile transition at temperature of around 160°C, remarkably lower than that of bulk Ag. The obtained Young's modulus and shear modulus values indicate obvious softening with increasing temperature, together with a remarkable decrease in Poisson's ratio. These plastic behaviors at elevated temperature can be explained based on Coble creep in the microporous network structure. Fracture surfaces after tensile and shear tests indicated unique features on scanning electron microscopy, reflecting the variation in the ductile behavior with the test temperature. Furthermore, these temperature-dependent mechanical parameters were employed in three-dimensional finite-element analysis of the thermomechanical stress distribution in wide-bandgap semiconductor module structures including Ag paste die attach of different sizes. Detailed thermal stress analysis enabled precise evaluation of the packaging design for wide-bandgap semiconductor modules for use in high-temperature applications.

  1. Mechanical Deformation of Sintered Porous Ag Die Attach at High Temperature and Its Size Effect for Wide-Bandgap Power Device Design

    Science.gov (United States)

    Chen, Chuantong; Nagao, Shijo; Zhang, Hao; Jiu, Jinting; Sugahara, Tohru; Suganuma, Katsuaki; Iwashige, Tomohito; Sugiura, Kazuhiko; Tsuruta, Kazuhiro

    2017-03-01

    The mechanical properties of sintered Ag paste with microporous structure have been investigated by tensile and shear tests, focusing on the temperature-dependent plastic deformation at various temperatures from 25°C to 300°C, corresponding to the target operating temperature range of emerging wide-bandgap semiconductor devices. Specimens were prepared by sintering hybrid Ag paste consisting of microflake and submicron spherical Ag particles, simulating a typical bonding process for power semiconductor die attach. Mechanical tests revealed that the unique microstructure caused a brittle-to-ductile transition at temperature of around 160°C, remarkably lower than that of bulk Ag. The obtained Young's modulus and shear modulus values indicate obvious softening with increasing temperature, together with a remarkable decrease in Poisson's ratio. These plastic behaviors at elevated temperature can be explained based on Coble creep in the microporous network structure. Fracture surfaces after tensile and shear tests indicated unique features on scanning electron microscopy, reflecting the variation in the ductile behavior with the test temperature. Furthermore, these temperature-dependent mechanical parameters were employed in three-dimensional finite-element analysis of the thermomechanical stress distribution in wide-bandgap semiconductor module structures including Ag paste die attach of different sizes. Detailed thermal stress analysis enabled precise evaluation of the packaging design for wide-bandgap semiconductor modules for use in high-temperature applications.

  2. Molecular Modeling in Drug Design for the Development of Organophosphorous Antidotes/Prophylactics

    Science.gov (United States)

    1986-05-01

    5012 61102A 1102BS11 EB 025 11. TITLE (Include Security Classification) Molecular Modeling in Drug Design for the Development of Organophosphorous...t ....................................., ’ i.° AD MOLECULAR MODELING IN DRUG DESIGN FOR THE DEVELOPMENT OF ORGANOPHOSPHOROUS ANTIDOTES...Reed, W.J. Murray, E.B. Roche and L.N. Donelsmith, Gen. Pharmac., 12, 177-185 (1981). 5. L.B.Kier, "Molecular Orbital Theory in Drug Design ", Academic

  3. Paternal Attachment, Parenting Beliefs and Children's Attachment

    Science.gov (United States)

    Howard, Kimberly S.

    2010-01-01

    Relationships between fathers' romantic attachment style, parenting beliefs and father-child attachment security and dependence were examined in a diverse sample of 72 fathers of young children. Paternal romantic attachment style was coded based on fathers' endorsement of a particular style represented in the Hazan and Shaver Three-Category…

  4. Strategy for Molecular Design of Photochromic Diarylethenes Having Thermal Functionality.

    Science.gov (United States)

    Kitagawa, Daichi; Kobatake, Seiya

    2016-08-01

    Thermal reactivities of photochromic diarylethene closed-ring isomers can be controlled by the introduction of substituents at the reactive positions. Diarylethenes having bulky alkyl groups undergo thermal cycloreversion reactions. When bulky alkoxy groups are introduced, the diarylethenes have both thermal cycloreversion reactivities and low photocycloreversion quantum yields. Such photochromic compounds can be applied to thermally reusable photoresponsive-image recordings. The thermal cycloreversion reactivity of the closed-ring isomers can be evaluated using specific steric substituent constants and be correlated with the parameters. By introduction of trimethylsilyl or methoxymethyl groups at the reactive positions, the diarylethene closed-ring isomers undergo thermal irreversible reactions to produce by-products at high temperatures. These diarylethenes may be useful for secret-image recordings. Furthermore, thiophene-S,S-dioxidized diarylethenes having secondary alkyl groups at the reactive positions undergo thermal by-product formation reactions, in addition to the photostability of the colored closed-ring isomers. Such materials may be used for light-starting thermosensors. The thermal by-product formation reactivity can be evaluated by the specific substituent constants and theoretical calculations of quantum chemistry. These results supply the strategy for the molecular design of the photochromic diarylethenes having thermal functionality.

  5. Molecular Design of Trypsin Towards High Substrate Selectivity

    Institute of Scientific and Technical Information of China (English)

    来鲁华; 王彦力; 徐筱杰; 唐有祺; 倪逸声; 张龙翔

    1994-01-01

    Molecular design of trypsin mutants towards higher substrate specificity for arginine or ly-sine type substrates was studied. The difference in side chain pKa of arginine and lysine was utilized in redesigning trypsin. If the enzyme could react effectively at a pH higher than lysine’s pKa but lower than that of arginine, it would react more selectively with arginine-type substrates, since in that pH range, the side chain of arginie remain protonated, while that of lysine is deprotonated. For trypsin. the change of histidine (57)’s pKa reflects the shift in reaction optimum pH. Electrostatic calculations showed that when surface positive residues were mutated into neutral or negative ones, the pKa of histidine(57) would be raised and those surface charges within a cone of 70 degree around histidine(57) have strong influence on its pKa. Several sites were suggested in rat trypsin which might serve as potential mutation locations to make trypsin active at a higher pH, thus more selective towards arginine t

  6. 30 CFR 75.1436 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 75.1436 Section 75.1436... attachment. (a) For drum end attachment, wire rope shall be attached— (1) Securely by clips after making one... that the attachment is a design feature of the hoist drum. Design feature means either the...

  7. Property Integration - A New Approach for Simultaneous Solution of Process and Molecular Design Problems

    DEFF Research Database (Denmark)

    concepts are employed to identify optimal properties without commitment to specific species. Subsequently, group contribution methods and molecular design techniques are employed to solve the reverse property prediction problem to design molecules possessing the optimal properties....

  8. Design and construction of a VHGT-attached WDM-type triplex transceiver module using polymer PLC hybrid integration technology

    Science.gov (United States)

    Jerábek, Vitezslav; Hüttel, Ivan; Prajzler, Václav; Busek, K.; Seliger, P.

    2008-11-01

    We report about design and construction of the bidirectional transceiver TRx module for subscriber part of the passive optical network PON for a fiber to the home FTTH topology. The TRx module consists of a epoxy novolak resin polymer planar lightwave circuit (PLC) hybrid integration technology with volume holographic grating triplex filter VHGT, surface-illuminated photodetectors and spot-size converted Fabry-Pérot laser diode in SMD package. The hybrid PLC has composed from a two parts-polymer optical waveguide including VHGT filter section and a optoelectronic microwave section. The both parts are placed on the composite substrate.

  9. Design and Synthesis of Chiral Molecular Tweezers Based on Deoxycholic Acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A series of new chiral molecular tweezers have been designed and synthesized by using deoxycholic acid as spacer and aromatic amines as arms.Instead of using toxic phosgene,the triphosgene was employed in synthesis of the molecular tweezers receptors.These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

  10. Combining docking and molecular dynamic simulations in drug design.

    Science.gov (United States)

    Alonso, Hernán; Bliznyuk, Andrey A; Gready, Jill E

    2006-09-01

    A rational approach is needed to maximize the chances of finding new drugs, and to exploit the opportunities of potential new drug targets emerging from genomic and proteomic initiatives, and from the large libraries of small compounds now readily available through combinatorial chemistry. Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery. This happy outcome results from development of more accurate and reliable algorithms, use of more thoughtfully planned strategies to apply them, and greatly increased computer power to allow studies with the necessary reliability to be performed. Our review focuses on applications and protocols, with the main emphasis on critical analysis of recent studies where docking calculations and molecular dynamics (MD) simulations were combined to dock small molecules into protein receptors. We highlight successes to demonstrate what is possible now, but also point out drawbacks and future directions. The review is structured to lead the reader from the simpler to more compute-intensive methods. Thus, while inexpensive and fast docking algorithms can be used to scan large compound libraries and reduce their size, more accurate but expensive MD simulations can be applied when a few selected ligand candidates remain. MD simulations can be used: during the preparation of the protein receptor before docking, to optimize its structure and account for protein flexibility; for the refinement of docked complexes, to include solvent effects and account for induced fit; to calculate binding free energies, to provide an accurate ranking of the potential ligands; and in the latest developments, during the docking process itself to find the binding site and correctly dock the ligand a priori.

  11. Theory for strength and stability of an unusual "ligand-receptor" bond: a microtubule attached to a wall by molecular motor tethers

    CERN Document Server

    Ghanti, Dipanwita

    2016-01-01

    A microtubule (MT) is a tubular stiff filament formed by a hierarchical organization of tubulin proteins. We develop a stochastic kinetic model for studying the strength and stability of a pre-formed attachment of a MT with a rigid wall where the MT is tethered to the wall by a group of motor proteins. Such an attachment, formed by the specific interactions between the MT and the motors, is an analog of ligand-receptor bonds, the MT and the motors anchored on the wall being the counterparts of the ligand and receptors, respectively. However, unlike other ligands, the length of a MT can change with time because of its polymerization-depolymerization kinetics. The simple model developed here is motivated by the MTs linked to the cell cortex by dynein motors. We present the theory for both force-ramp and force-clamp conditions. In the force-ramp protocol we investigate the strength of the attachment by assuming imposition of a time-dependent external load tension that increases linearly with time till the attach...

  12. Attachment behavior in rats

    NARCIS (Netherlands)

    Sigling, H.O.

    2009-01-01

    This thesis describes studies into the rat as an animal model for attachment, along the lines of Bowlby's attachment theory. First, the relation between attachment and human psychopathology is reviewed. The conclusion is that psychopathology is more frequent in insecure attached persons and that the

  13. Design of chiral dimesogens containing cholesteryl groups; formation of new molecular organizations and their application to molecular photonics.

    Science.gov (United States)

    Mallia, V Ajay; Tamaoki, Nobuyuki

    2004-02-20

    Photoresponsive liquid crystals and organogels are finding increasing application in information technology and photonics. In this tutorial review, the authors describe how weak intermolecular interactions facilitate molecular organization of cholesterol-containing dimesogens to form such materials. Design considerations and photoresponsive properties of both organogels and glassy liquid crystals are discussed and their applications to molecular photonics highlighted. The review will be of value to readers interested in the development of new materials which respond to the different properties of light.

  14. Molecular-level Design of Heterogeneous Chiral Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Gellman, Andrew John [Carnegie Mellon University; Sholl, David S. [Georgia Institute of Technology; Tysoe, Wilfred T. [University of Wisconsin - Milwaukee; Zaera, Francisco [University of California at Riverside

    2013-04-28

    Understanding and controlling selectivity is one of the key challenges in heterogeneous catalysis. Among problems in catalytic selectivity enantioselectivity is perhaps the most the most challenging. The primary goal of the project on “Molecular-level Design of Heterogeneous Chiral Catalysts” is to understand the origins of enantioselectivity on chiral heterogeneous surfaces and catalysts. The efforts of the project team include preparation of chiral surfaces, characterization of chiral surfaces, experimental detection of enantioselectivity on such surfaces and computational modeling of the interactions of chiral probe molecules with chiral surfaces. Over the course of the project period the team of PI’s has made some of the most detailed and insightful studies of enantioselective chemistry on chiral surfaces. This includes the measurement of fundamental interactions and reaction mechanisms of chiral molecules on chiral surfaces and leads all the way to rationale design and synthesis of chiral surfaces and materials for enantioselective surface chemistry. The PI’s have designed and prepared new materials for enantioselective adsorption and catalysis. Naturally Chiral Surfaces • Completion of a systematic study of the enantiospecific desorption kinetics of R-3-methylcyclohexanone (R-3-MCHO) on 9 achiral and 7 enantiomeric pairs of chiral Cu surfaces with orientations that span the stereographic triangle. • Discovery of super-enantioselective tartaric acid (TA) and aspartic acid (Asp) decomposition as a result of a surface explosion mechanism on Cu(643)R&S. Systematic study of super-enantiospecific TA and Asp decomposition on five enantiomeric pairs of chiral Cu surfaces. • Initial observation of the enantiospecific desorption of R- and S-propylene oxide (PO) from Cu(100) imprinted with {3,1,17} facets by L-lysine adsorption. Templated Chiral Surfaces • Initial observation of the enantiospecific desorption of R- and S-PO from Pt(111) and Pd(111

  15. Synthesis and Evaluation of CO2 Thickeners Designed with Molecular Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Robert Enick; Erick Beckman; J. Karl Johnson

    2009-08-31

    The objective of this research was to use molecular modeling techniques, coupled with our prior experimental results, to design, synthesize and evaluate inexpensive, non-fluorous carbon dioxide thickening agents. The first type of thickener that was considered was associating polymers. Typically, these thickeners are copolymers that contain a highly CO{sub 2}-philic monomer, and a small concentration of a CO{sub 2}-phobic associating monomer. Yale University was solely responsible for the synthesis of a second type of thickener; small, hydrogen bonding compounds. These molecules have a core that contains one or more hydrogen-bonding groups, such as urea or amide groups. Non-fluorous, CO{sub 2}-philic functional groups were attached to the hydrogen bonding core of the compound to impart CO{sub 2} stability and macromolecular stability to the linear 'stack' of these compounds. The third type of compound initially considered for this investigation was CO{sub 2}-soluble surfactants. These surfactants contain conventional ionic head groups and composed of CO{sub 2}-philic oligomers (short polymers) or small compounds (sugar acetates) previously identified by our research team. Mobility reduction could occur as these surfactant solutions contacted reservoir brine and formed mobility control foams in-situ. The vast majority of the work conducted in this study was devoted to the copolymeric thickeners and the small hydrogen-bonding thickeners; these thickeners were intended to dissolve completely in CO{sub 2} and increase the fluid viscosity. A small but important amount of work was done establishing the groundwork for CO{sub 2}-soluble surfactants that reduced mobility by generating foams in-situ as the CO{sub 2}+surfactant solution mixed with in-situ brine.

  16. Depression and attachment problems.

    OpenAIRE

    Pettem, O; M. West; Mahoney, A; Keller, A.

    1993-01-01

    This study investigated the characteristics related to attachment of 42 depressed psychiatric patients and 42 non-depressed psychiatric controls. The depressed subjects demonstrated an anxious pattern of attachment, characterized by either intense care-seeking in relation to their attachment figure or angry withdrawal from their attachment figure when their desire for security was frustrated. The results are discussed in terms of Bowlby's attachment construct.

  17. The Design of Molecular Hosts, Guests, and Their Complexes.

    Science.gov (United States)

    Cram, Donald J.

    1988-01-01

    Describes the origins, definitions, tools, and principles of host-guest chemistry. Gives examples of chiral recognition in complexation, of partial transacylase mimics, of caviplexes, and of a synthetic molecular cell. (Author/RT)

  18. Adult attachment styles

    Directory of Open Access Journals (Sweden)

    Maša Žvelc

    2007-01-01

    Full Text Available Theory of attachment primarily described early relationships between a child and his caretakers. In the last twenty years there is a growing interest in adult attachment research. Theories and research findings of adult attachment stem from two different methodological approaches. The first approach measures adult attachment through Adult Attachment Interview (AAI; Main, 1991 where the attachment is assessed through the narratives of adult people of their early child experiences with their primary caretakers. The second approach measures adult attachment with the help of self-evaluative questionnaires, developed by (a Hazan and Shaver (1987 who started this approach in the field of personality and social psychology, and (b Bartholomew and Horowitz (1991. Research shows that there is significant correlation between early and adult attachment style. Attachment styles are passed from generation to generation. Basic adult attachment styles are: securely attached, preoccupied, fearful-avoidant, dismissing-avoidant and disorganized. Previous research using Barholomew and Horowitz (1991 Relationship Questionnaire on 176 Slovenian students showed that 48% students are securely attached, 29% are fearful-avoidant, 10% are dismissing-avoidant, and 13% have preoccupied attachment style. Theory of attachment is very useful for understanding the behavior and subjective experiences of children and adults. It is applicable to different contexts (psychotherapy, counseling, education .... The paper proposes further research focused on integration of adult attachment styles and types of object relations measured by Test of object relations (Žvelc, 1998 and Pictorial test of Separation and Individuation (Žvelc, 2003.

  19. Molecular-Level Design of Heterogeneous Chiral Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Francisco Zaera

    2012-03-21

    The following is a proposal to continue our multi-institutional research on heterogeneous chiral catalysis. Our team combines the use of surface-sensitive analytical techniques for the characterization of model systems with quantum and statistical mechanical calculations to interpret experimental data and guide the design of future research. Our investigation focuses on the interrelation among the three main mechanisms by which enantioselectivity can be bestowed to heterogeneous catalysts, namely: (1) by templating chirality via the adsorption of chiral supramolecular assemblies, (2) by using chiral modifiers capable of forming chiral complexes with the reactant and force enantioselective surface reactions, and (3) by forming naturally chiral surfaces using imprinting chiral agents. Individually, the members of our team are leaders in these various aspects of chiral catalysis, but the present program provides the vehicle to generate and exploit the synergies necessary to address the problem in a comprehensive manner. Our initial work has advanced the methodology needed for these studies, including an enantioselective titration procedure to identify surface chiral sites, infrared spectroscopy in situ at the interface between gases or liquids and solids to mimic realistic catalytic conditions, and DFT and Monte Carlo algorithms to simulate and understand chirality on surfaces. The next step, to be funded by the monies requested in this proposal, is to apply those methods to specific problems in chiral catalysis, including the identification of the requirements for the formation of supramolecular surface structures with enantioselective behavior, the search for better molecules to probe the chiral nature of the modified surfaces, the exploration of the transition from supramolecular to one-to-one chiral modification, the correlation of the adsorption characteristics of one-to-one chiral modifiers with their physical properties, in particular with their configuration

  20. Molecular Lego: design of molecular assemblies of P450 enzymes for nanobiotechnology.

    Science.gov (United States)

    Gilardi, Gianfranco; Meharenna, Yergalem T; Tsotsou, Georgia E; Sadeghi, Sheila J; Fairhead, Michael; Giannini, Silva

    2002-01-01

    This paper reports on the application of the molecular Lego approach to P450 enzymes. Protein domains are used as catalytic (P450 BM3 haem domain and human P450 2E1) or electron transfer (flavodoxin and P450 BM3 reductase) modules. The objectives are to build assemblies with improved electrochemical properties, to construct soluble human P450 enzymes, and to generate libraries of new P450 catalytic modules based on P450 BM3. A rationally designed, gene-fused assembly (BMP-FLD) was obtained from the soluble haem domain of cytochrome P450 BM3 from Bacillus megaterium (BMP) and flavodoxin from Desulfovibrio vulgaris (FLD). The assembly was expressed successfully and characterised in its active form, displaying improved electrochemical properties. Solubilisation of the human, membrane-bound P450 2E1 (2E1) was achieved by fusing key elements of the 2E1 enzyme with selected parts of P450 BM3. An assembly containing the first 54 residues of P450 BM3, the whole sequence of P450 2E1 from residue 81 and the reductase domain of P450 BM3 was constructed. The 2E1-BM3 assembly was successfully expressed in the cytosol of Escherichia coli. The soluble form of 2E1-BM3 was reduced in carbon monoxide atmosphere and displayed the typical absorption peak at 450 nm, characteristic of a folded and active P450 enzyme. Finally, the alkali method previously developed in this laboratory was used to screen for P450 activity within a library of random mutants of P450 BM3. A number of variants active towards non-physiological substrates, such as pesticides and polyaromatic hydrocarbons were identified, providing new P450 catalytic modules. The combination of these three areas of research provide interesting tools for exploitation in nanobiotechnology.

  1. Molecular design of electron transport with orbital rule: toward conductance-decay free molecular junctions.

    Science.gov (United States)

    Tada, Tomofumi; Yoshizawa, Kazunari

    2015-12-28

    In this study, we report our viewpoint of single molecular conductance in terms of frontier orbitals. The orbital rule derived from orbital phase and amplitude is a powerful guideline for the qualitative understanding of molecular conductance in both theoretical and experimental studies. The essence of the orbital rule is the phase-related quantum interference, and on the basis of this rule a constructive or destructive pathway for electron transport is easily predicted. We have worked on the construction of the orbital rule for more than ten years and recently found from its application that π-stacked molecular junctions fabricated experimentally are in line with the concept for conductance-decay free junctions. We explain the orbital rule using benzene molecular junctions with the para-, meta- and ortho-connections and discuss linear π-conjugated chains and π-stacked molecular junctions with respect to their small decay factors in this manuscript.

  2. 30 CFR 56.19026 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 56.19026 Section 56.19026... Ropes § 56.19026 Drum end attachment. (a) For drum end attachment, wire rope shall be attached— (1... bolts, clamps, or wedges, provided that the attachment is a design feature of the hoist drum....

  3. 30 CFR 57.19026 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 57.19026 Section 57.19026... Wire Ropes § 57.19026 Drum end attachment. (a) For drum end attachment, wire rope shall be attached— (1... bolts, clamps, or wedges, provided that the attachment is a design feature of the hoist drum....

  4. Reactive Attachment Disorder

    Science.gov (United States)

    ... Reactive Attachment Disorder and Disinhibited Social Engagement Disorder. Reactive Attachment Disorder (RAD) Children with RAD are less likely to interact with other people because of negative experiences with adults in their early years. They have difficulty calming ...

  5. Generic Mathematical Programming Formulation and Solution for Computer-Aided Molecular Design

    OpenAIRE

    2015-01-01

    This short communication presents a generic mathematical programming formulation for Computer-Aided Molecular Design (CAMD). A given CAMD problem, based on target properties, is formulated as a Mixed Integer Linear/Non-Linear Program (MILP/MINLP). The mathematical programming model presented here, which is formulated as an MILP/MINLP problem, considers first-order and second-order molecular groups for molecular structure representation and property estimation. It is shown that various CAMD pr...

  6. Belt attachment and system

    Science.gov (United States)

    Schneider, Abraham D.; Davidson, Erick M.

    2016-02-02

    Disclosed herein is a belt assembly including a flexible belt with an improved belt attachment. The belt attachment includes two crossbars spaced along the length of the belt. The crossbars retain bearings that allow predetermined movement in six degrees of freedom. The crossbars are connected by a rigid body that attaches to the bearings. Implements that are attached to the rigid body are simply supported but restrained in pitching rotation.

  7. Attachment Without Fear

    OpenAIRE

    2009-01-01

    John Bowlby hypothesized an attachment system that interacts with caregiving, exploration, and fear systems in the brain, with a particular emphasis on fear. Neurobiological research confirms many of his hypotheses and also raises some new questions. A psychological model based on this neurobiological research is presented here. The model extends conventional attachment theory by describing additional attachment processes independent of fear. In this model, the attachment elements of trust, o...

  8. Attachment Without Fear.

    Science.gov (United States)

    Bell, David C

    2009-12-01

    John Bowlby hypothesized an attachment system that interacts with caregiving, exploration, and fear systems in the brain, with a particular emphasis on fear. Neurobiological research confirms many of his hypotheses and also raises some new questions. A psychological model based on this neurobiological research is presented here. The model extends conventional attachment theory by describing additional attachment processes independent of fear. In this model, the attachment elements of trust, openness, and dependence interact with the caregiving elements of caring, empathy, and responsibility.

  9. Molecular Orbital Based Design Guidelines for Hypergolic Energetic Ionic Liquids

    Science.gov (United States)

    2015-01-01

    should be synthesized to further validate our probabilistic approach for identifying EIL hypergols. DMP is one anion that has a lower “energy gap”, but...orbitals (HOMO) of the anions for a series of ionic liquids and the lowest occupied molecular orbital (LUMO) of HNO3, and variation in the computed...relative heats of formation, DHf, of these anions to develop correlations to predict hypergol activity between an ionic liquid fuel and nitric acid as

  10. A prospective overview of the essential requirements in molecular modeling for nanomedicine design.

    Science.gov (United States)

    Kumar, Pradeep; Khan, Riaz A; Choonara, Yahya E; Pillay, Viness

    2013-05-01

    Nanotechnology has presented many new challenges and opportunities in the area of nanomedicine design. The issues related to nanoconjugation, nanosystem-mediated targeted drug delivery, transitional stability of nanovehicles, the integrity of drug transport, drug-delivery mechanisms and chemical structural design require a pre-estimated and determined course of assumptive actions with property and characteristic estimations for optimal nanomedicine design. Molecular modeling in nanomedicine encompasses these pre-estimations and predictions of pertinent design data via interactive computographic software. Recently, an increasing amount of research has been reported where specialized software is being developed and employed in an attempt to bridge the gap between drug discovery, materials science and biology. This review provides an assimilative and concise incursion into the current and future strategies of molecular-modeling applications in nanomedicine design and aims to describe the utilization of molecular models and theoretical-chemistry computographic techniques for expansive nanomedicine design and development.

  11. Design and Synthesis of Novel Molecular Tweezers Derived from Chenodeoxycholic Acid

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang ZHAO; Qi Ming MU; Shu Hua CHEN

    2004-01-01

    A novel type of chiral molecular tweezers has been designed and synthesized by using chenodeoxy cholic acid as spacer and the aromatic compounds as arm. Their structures were characterized by 1HNMR, IR, MS spectra and elemental analysis. These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

  12. Digital learning material for experimental design and model building in molecular biology

    NARCIS (Netherlands)

    Aegerter-Wilmsen, T.

    2005-01-01

    Designing experimental approaches is a major cognitive skill in molecular biology research, and building models, including quantitative ones, is a cognitive skill which is rapidly gaining importance. Since molecular biology education at university level is aimed at educating future researchers, we c

  13. Design, synthesis, and biological evaluation of potent discodermolide fluorescent and photoaffinity molecular probes.

    Science.gov (United States)

    Smith, Amos B; Rucker, Paul V; Brouard, Ignacio; Freeze, B Scott; Xia, Shujun; Horwitz, Susan Band

    2005-11-10

    [structure: see text] The design, synthesis, and biological evaluation of a series of (+)-discodermolide molecular probes possessing photoaffinity and fluorescent appendages has been achieved. Stereoselective olefin cross-metathesis comprised a key tactic for construction of two of the molecular probes. Three photoaffinity probes were radiolabeled with tritium.

  14. Design and synthesis of novel chiral molecular tweezers based on deoxycholic acid

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang Zhao; Xing Li Liu; Yi Zhong

    2008-01-01

    A novel type of chiral molecular tweezers has been designed and synthesized by using deoxycholic acid as backbone and ethanoyl and the chiral unsymmetrical urea unit as arms. Their structures were characterized by 1H NMR, IR, MS spectra and elemental analysis. These molecular tweezers showed good binding ability for neutral molecules and chiral molecules.

  15. Attachment over Time.

    Science.gov (United States)

    Lewis, Michael; Feiring, Candice; Rosenthal, Saul

    2000-01-01

    Examined continuity in attachment classification from infancy through adolescence and related it to autobiographical memories of childhood, divorce, and maladjustment in white middle-class children. Found no continuity in attachment classification from 1 to 18 years and no relation between infant attachment status and adolescent adjustment.…

  16. Attachment and Psychopathology

    Directory of Open Access Journals (Sweden)

    Mehmet Fatih Ustundag

    2011-06-01

    Full Text Available The type of attachment defined in the early stages of life and thought to be continuous, is a phenomenon that shapes the pattern of how a person makes contact with others. The clinical appearance of every type of attachment is different and each one has prospective and retrospective phenomenological reflections. In all stages of life and in close relationships, it can be observed if a person gets in close contact with someone else and if this relation bears supportive and protective qualities. According to attachment theorists, once it is defined as safe or unsafe during nursing period, it shows little change. Starting from Bowlby’s work, unsafe attachment type is considered as the determining factor of psychopathology in the later periods of life, while safe attachment is considered as in relation with healthy processes. The nature’s original model is safe attachment. Anxious/indecisive attachment, an unsafe attachment type, is associated with anxiety disorders and depressive disorder, while avoidant attachment is associated with behavior disorder and other extroverted pathologies. Disorganized/disoriented attachment is considered to be together with dissociative disorder. The aim of this paper is to review attachment theory and the relation between attachment and psychopathology.

  17. An algebraic approach for simultaneous solution of process and molecular design problems

    Directory of Open Access Journals (Sweden)

    S. Bommareddy

    2010-09-01

    Full Text Available The property integration framework has allowed for simultaneous representation of processes and products from a properties perspective and thereby established a link between molecular and process design problems. The simultaneous approach involves solving two reverse problems. The first reverse problem identifies the property targets corresponding to the desired process performance. The second reverse problem is the reverse of a property prediction problem, which identifies the molecular structures that match the targets identified in the first problem. Group Contribution Methods (GCM are used to form molecular property operators that will be used to track properties. Earlier contributions in this area have worked to include higher order estimation of GCM for solving the molecular design problem. In this work, the accuracy of the property prediction is further enhanced by improving the techniques to enumerate higher order groups. Incorporation of these higher order enumeration techniques increases the efficiency of property prediction and thus the application range of the group contribution methods in molecular design problems. Successful tracking of properties is the key in applying the reverse problem formulation for integrated process and product design problems. An algebraic technique has been developed for solving process and molecular design problems simultaneously. Since both process and molecular property operators target the same optimum process performance, the set of inequality expressions can be solved simultaneously to identify the molecules that meet the desired process performance. Since this approach is based on an algebraic algorithm, any number of properties can be tracked simultaneously.

  18. Design and synthesis of fluorescent and biotin tagged probes for the study of molecular actions of FAF1 inhibitor.

    Science.gov (United States)

    Yoo, Sung-eun; Yu, Changsun; Jung, SeoHee; Kim, Eunhee; Kang, Nam Sook

    2016-02-15

    To study the molecular action of ischemic Fas-mediated cell death inhibitor, we prepared fluorescent-tagged and biotin-tagged probes of the potent inhibitor, KR-33494, of ischemic cell death. We used the molecular modeling technique to find the proper position for attaching those probes with minimum interference in the binding process of probes with Fas-mediated cell death target, FAF1.

  19. Resonance Energy Transfer-Based Molecular Switch Designed Using a Systematic Design Process Based on Monte Carlo Methods and Markov Chains

    Science.gov (United States)

    Rallapalli, Arjun

    A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical. In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications. We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the

  20. Attachment Security and Pain

    DEFF Research Database (Denmark)

    Andersen, Tonny Elmose; Lahav, Yael; Defrin, Ruth;

    2015-01-01

    The present study assesses for the first time, the possible disruption effect of posttraumatic stress symptoms (PTSS) with regard to the protective role of attachment on pain, among ex-POWs. While secure attachment seems to serve as a buffer, decreasing the perception of pain, this function may...... be disrupted by PTSS. The study sample included 104 subjects who were combat veterans of the 1973 Yom Kippur War comprising of 60 male ex-prisoners of war (ex-POWs) and 44 comparable male combat veterans. Both attachment and pain were investigated experimentally in the laboratory and via questionnaires. We...... found that ex-POWs showed higher levels of clinical pain and attachment insecurities compared to controls. Moreover, attachment avoidance and soothing effect of attachment (SEA) were both associated with lower levels of clinical pain. Most importantly, PTSS moderated the associations between attachment...

  1. Molecular design, synthesis and evaluation of chemical biology tools

    NARCIS (Netherlands)

    Hoogenboom, Jorin

    2017-01-01

    Chapter 1 provides a perspective of synthetic organic chemistry as a discipline involved in the design, synthesis and evaluation of complex molecules. The reader is introduced with a brief history of synthetic organic chemistry, all the while dealing with different aspects of synthe

  2. GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects

    DEFF Research Database (Denmark)

    Krogsgaard-Larsen, P; Frølund, B; Frydenvang, Karla Andrea

    2000-01-01

    GABAA receptor agonists. The availability of these compounds made it possible to study the pharmacology of the GABA uptake systems and the GABAA receptors separately. Based on extensive cellular and molecular pharmacological studies using 23, 24, and a number of mono- and bicyclic analogues, it has been...... demonstrated that neuronal and glial GABA transport mechanisms have dissimilar substrate specificities. With GABA transport mechanisms as pharmacological targets, strategies for pharmacological interventions with the purpose of stimulating GABA neurotransmission seem to be (1) effective blockade of neuronal...... recently been reported as the most selective glial GABA uptake inhibitor so far known and may be a useful tool for further elucidation of the pharmacology of GABA transporters. In recent years, a variety of lipophilic analogues of the amino acids 23 and 24 have been developed, and one of these compounds...

  3. Remedial action plan and site design for stabilization of the inactive Uranium Mill Tailing site Maybell, Colorado. Attachment 3, ground water hydrology report, Attachment 4, water resources protection strategy. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    The U.S. Environmental Protection Agency (EPA) has established health and environmental regulations to correct and prevent ground water contamination resulting from former uranium processing activities at inactive uranium processing sites (40 CFR Part 192 (1993)) (52 FR 36000 (1978)). According to the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978 (42 USC {section} 7901 et seq.), the U.S. Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has decided that each assessment will include information on hydrogeologic site characterization. The water resources protection strategy that describes the proposed action compliance with the EPA ground water protection standards is presented in Attachment 4, Water Resources Protection Strategy. Site characterization activities discussed in this section include the following: (1) Definition of the hydrogeologic characteristics of the environment, including hydrostratigraphy, aquifer parameters, areas of aquifer recharge and discharge, potentiometric surfaces, and ground water velocities. (2) Definition of background ground water quality and comparison with proposed EPA ground water protection standards. (3) Evaluation of the physical and chemical characteristics of the contaminant source and/or residual radioactive materials. (4) Definition of existing ground water contamination by comparison with the EPA ground water protection standards. (5) Description of the geochemical processes that affect the migration of the source contaminants at the processing site. (6) Description of water resource use, including availability, current and future use and value, and alternate water supplies.

  4. Attachment theory: A review of research

    Directory of Open Access Journals (Sweden)

    Polovina Nada

    2005-01-01

    Full Text Available Research of attachment is numerous and versatile. They differ according to problems addressed, methodology applied (longitudinal studies, studies with horizontal designs, different instruments used, different methods of data analysis, and characteristics of samples involved (concerning age socio/economic status, family ecology. The research is commonly relied on the core assumptions of the theory itself, and the shared characteristic is orientation to explore complex phenomena of human experience and functioning. From the vast variety of research only those who most directly test the basic assumptions of the attachment theory are focused and addressed in the paper: representation of patterns of attachment in the childhood and adulthood, stability and change of attachment security from infancy to early adulthood, transgenerational transmission of attachment characteristics, the place and the role of attachment behavioral system in the personality development. The aim of the paper is to highlight the basic research and theory issues and directions, and illustrate them with concrete research date.

  5. A Multi-Step and Multi-Level Approach for Computer Aided Molecular Design

    DEFF Research Database (Denmark)

    Harper, Peter Mathias; Gani, Rafiqul

    2001-01-01

    . The problem formulation step incorporates a knowledge base for the identification and setup of the design criteria. Candidate compounds are identified using a multi-level generate and test CAMD solution algorithm capable of designing molecules having a high level of molecular detail. A post solution step...

  6. Molecular Design and Synthesis of New Noncrystalline Solids

    Science.gov (United States)

    1981-06-01

    few oddities like chalcogenides of metalloids ). 2 Since 1960 when this picture held, both the reasons enumerated have become invalid. Solid state...deposition interaction of the film with oxygen and water vapor through void, or low density, regions 21’ 22. The abundance of these clusters is 24 + 80...deposition treatment and usualYy not measured. Unless designated as stoichiometric-WO3, the term We3 should be assumed to mean the variable composition

  7. A Multi-step and Multi-level approach for Computer Aided Molecular Design

    DEFF Research Database (Denmark)

    A general multi-step approach for setting up, solving and solution analysis of computer aided molecular design (CAMD) problems is presented. The approach differs from previous work within the field of CAMD since it also addresses the need for a computer aided problem formulation and result analysis....... The problem formulation step incorporates a knowledge base for the identification and setup of the design criteria. Candidate compounds are identified using a multi-level generate and test CAMD solution algorithm capable of designing molecules having a high level of molecular detail. A post solution step...... using an Integrated Computer Aided System (ICAS) for result analysis and verification is included in the methodology. Keywords: CAMD, separation processes, knowledge base, molecular design, solvent selection, substitution, group contribution, property prediction, ICAS Introduction The use of Computer...

  8. Blade attachment assembly

    Science.gov (United States)

    Garcia-Crespo, Andres Jose; Delvaux, John McConnell; Miller, Diane Patricia

    2016-05-03

    An assembly and method for affixing a turbomachine rotor blade to a rotor wheel are disclosed. In an embodiment, an adaptor member is provided disposed between the blade and the rotor wheel, the adaptor member including an adaptor attachment slot that is complementary to the blade attachment member, and an adaptor attachment member that is complementary to the rotor wheel attachment slot. A coverplate is provided, having a coverplate attachment member that is complementary to the rotor wheel attachment slot, and a hook for engaging the adaptor member. When assembled, the coverplate member matingly engages with the adaptor member, and retains the blade in the adaptor member, and the assembly in the rotor wheel.

  9. Chapter 6 – Computer-Aided Molecular Design and Property Prediction

    DEFF Research Database (Denmark)

    Gani, Rafiqul; Zhang, L.; Kalakul, Sawitree

    2017-01-01

    to meet the global challenges of resources, competition, and demand. Design/development of these products mostly follows experiment-based trial and error approaches. With the availability of reliable property prediction models, however, computer-aided techniques have become popular, at least...... for the initial stages of the design/development process. Therefore, computer-aided molecular design and property prediction techniques are two topics that play important roles in chemical product design, analysis, and application. In this chapter, an overview of the concepts, methods, and tools related...... to these two topics are given. In addition, a generic computer-aided framework for the design of molecules, mixtures, and blends is presented. The application of the framework is highlighted for molecular products through two case studies involving the design of refrigerants and surfactants....

  10. Positron-attachment to small molecules: Vibrational enhancement of positron affinities with configuration interaction level of multi-component molecular orbital approach

    Energy Technology Data Exchange (ETDEWEB)

    Tachikawa, Masanori [Quantum Chemistry Division, Graduate School of NanoBioScience, Yokohama City University, 22-2 Seto, Kanazawa, Yokohama 236-0027 (Japan)

    2015-12-31

    To theoretically demonstrate the binding of a positron to small polarized molecules, we have calculated the vibrational averaged positron affinity (PA) values along the local vibrational contribution with the configuration interaction level of multi-component molecular orbital method. This method can take the electron-positron correlation contribution into account through single electronic - single positronic excitation configurations. The PA values are enhanced by including the local vibrational contribution from vertical PA values due to the anharmonicity of the potential.

  11. Molecular Design of Near-IR Harvesting Unsymmetrical Squaraine Dyes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sanghoon; Mor, Gopal K.; Paulose, Maggie; Varghese, Oomman K.; Baik, Chul; Grimes, Craig A.

    2010-08-17

    The functionalized unsymmetrical benzothiazole squaraine organic sensitizers 5-carboxy-2-({3-[(3-hexylbenzothiazol-2(3H)-ylidene)methyl]-2-hydroxy-4-oxo-2-cyclobuten-1-ylidene}methyl)-1-hexyl-3,3-dimethyl-3H-indolium (hereafter named as SK-11) and 5-carboxy-2-({3-[(3-hexyl-5-methoxybenzothiazol-2(3H)-ylidene)methyl]-2-hydroxy-4-oxo-2-cyclobuten-1-ylidene}methyl)-1-hexyl-3,3-dimethyl-3H-indolium (coded as SK-12) are designed and developed to observe an intense and wider absorption band in the red/NIR wavelength region. DFT/TDDFT calculations have been performed on the two unsymmetrical squaraine sensitizers to gain insight into their electronic and optical properties. The utility of these dyes in solid state dye sensitized solar cells (SS-DSSCs) is demonstrated.

  12. Designing Electronic Components and Devices from Inorganic Molecular Scaffolds

    Science.gov (United States)

    2012-07-04

    CH3)3 1 Et3N,CuI Pd(OAc)3, PPh3 Trimethylsilyethyne Reflux 90oC, 24h PdCl2(PPh3)2 KOAc O-(triflate)-4- Bromo-8- Quinolinate Dioxane...triflate)-4- Bromo-8- Quinolinate Dioxane, reflux C8H17 H17C8 N OTf 3 8-MeO-Q C8H17H17C8 Br + 4 Pd(OAc)2 PPh3 Na2CO3 B(OH)2 (HO)2B Pd(PPh3)2Cl2...undergraduate research environment . Students designed and studied new and unique materials on the atomic scale that have desirable electronic and optical

  13. Final Report, "Molecular Design of Hydrocarbon Oxidation Catalytic Processes"

    Energy Technology Data Exchange (ETDEWEB)

    Professor Francisco Zaera

    2007-08-09

    The main goal of this project had been to use model systems to correlate selectivities in partial oxidation catalysis with the presence of specific sites on the surface of the catalyst. Extensive work was performed this year on characterizing oxygen-treated nickel surfaces by chemical means. Specifically, the surface chemistry of ammonia coadsorbed with atomic oxygen on Ni(110) single-crystal surfaces was studied by temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). It was determined that at intermediate oxygen coverages direct ammonia adsorption on nickel sites is suppressed, but a new high-temperature reaction regime is generated at 400 K where NHx surface fragments are rehydrogenated concurrently with the production of water and molecular hydrogen. The extensive isotope scrambling and hydrogen transfer seen from nitrogen- to oxygen-containing surface intermediates, and the optimum yields seen for this 400 K state at intermediate oxygen coverages, strongly suggest the direct interaction of the adsorbed ammonia with oxygen atoms at the end of the –Ni–O- rows that form upon reconstruction of the surface. Hydrogen transfer between ammonia and oxygen appears to take place directly via hydrogen bonding, and to be reversible but biased towards water formation. An equilibrium is reached between the produced water and the reacting surface oxygen and hydrogen. The strong influence of the OH surface groups on the thermal chemistry of the adsorbed ammonia was interpreted in terms of the adsorbing geometry of the OH groups on the surface, and of hydrogen bonding between adsorbed OH and NH3 species. In terms of alcohol reactivity, the adsorption of 2-iodoethanol, a precursor for the preparation of 2-hydroxyethyl and oxametallacycle surface species, was found to lead to two configurations involving either just the iodine atom or both iodine and hydroxyl ends of the molecule. A complex chemical behavior starts around 140 K with the

  14. On the Physical Design of Molecular Communication Receiver Based on Nanoscale Biosensors

    OpenAIRE

    2015-01-01

    1 On the Physical Design of Molecular Communication Receiver Based on Nanoscale Biosensors Murat Kuscu, Student Member, IEEE and Ozgur B. Akan, Fellow, IEEE Abstract—Molecular communications (MC), where molecules are used to encode, transmit, and receive information, is a promising means of enabling the coordination of nanoscale devices. The paradigm has been extensively studied from var-ious aspects, including channel modeling and noise analysis. Comparatively l...

  15. Longitudinal association between adolescent attachment, adult romantic attachment, and emotion regulation strategies.

    Science.gov (United States)

    Pascuzzo, Katherine; Cyr, Chantal; Moss, Ellen

    2013-01-01

    Attachment security towards parents and peers in adolescence, and romantic attachment styles and emotion regulation strategies in young adulthood, were evaluated using an eight-year longitudinal design. Fifty-six young adults completed the Inventory of Parent and Peer Attachment (IPPA) at age 14, and then, at age 22, the Experience in Close Relationships (ECR) and the Coping Inventory for Stressful Situations (CISS), an emotion regulation questionnaire concerning coping strategies, including task-oriented versus emotion-oriented foci. Results indicated that greater insecurity to parents and peers in adolescence predicted a more anxious romantic attachment style and greater use of emotion-oriented strategies in adulthood. Concurrently, anxious adult attachment style was related to more emotion-oriented strategies, whereas an avoidant attachment style was related to less support-seeking. Analyses also identified emotion-oriented coping strategies as a partial mediator of the link between adolescent attachment insecurity to parents and adult anxious attachment, and a complete mediator of the association between adolescent attachment insecurity to peers and adult anxious attachment. These findings support the core assumption of continuity in attachment theory, where relationships to parents influence close romantic relationships in adulthood.

  16. Molecular Design of Benzodithiophene-Based Organic Photovoltaic Materials.

    Science.gov (United States)

    Yao, Huifeng; Ye, Long; Zhang, Hao; Li, Sunsun; Zhang, Shaoqing; Hou, Jianhui

    2016-06-22

    Advances in the design and application of highly efficient conjugated polymers and small molecules over the past years have enabled the rapid progress in the development of organic photovoltaic (OPV) technology as a promising alternative to conventional solar cells. Among the numerous OPV materials, benzodithiophene (BDT)-based polymers and small molecules have come to the fore in achieving outstanding power conversion efficiency (PCE) and breaking 10% efficiency barrier in the single junction OPV devices. Remarkably, the OPV device featured by BDT-based polymer has recently demonstrated an impressive PCE of 11.21%, indicating the great potential of this class of materials in commercial photovoltaic applications. In this review, we offered an overview of the organic photovoltaic materials based on BDT from the aspects of backbones, functional groups, alkyl chains, and device performance, trying to provide a guideline about the structure-performance relationship. We believe more exciting BDT-based photovoltaic materials and devices will be developed in the near future.

  17. Generic Mathematical Programming Formulation and Solution for Computer-Aided Molecular Design

    DEFF Research Database (Denmark)

    Zhang, Lei; Cignitti, Stefano; Gani, Rafiqul

    2015-01-01

    This short communication presents a generic mathematical programming formulation for Computer-Aided Molecular Design (CAMD). A given CAMD problem, based on target properties, is formulated as a Mixed Integer Linear/Non-Linear Program (MILP/MINLP). The mathematical programming model presented here......, which is formulated as an MILP/MINLP problem, considers first-order and second-order molecular groups for molecular structure representation and property estimation. It is shown that various CAMD problems can be formulated and solved through this model....

  18. Pentameric models as alternative molecular targets for the design of new antiaggregant agents.

    Science.gov (United States)

    Barrera Guisasola, Exequiel E; Gutierrez, Lucas J; Andujar, Sebastián A; Angelina, Emilio; Rodríguez, Ana M; Enriz, Ricardo D

    2016-01-01

    The structure-based drug design has been an extremely useful technique used for searching and developing of new therapeutic agents in various biological systems. In the case of AD, this approach has been difficult to implement. Among other several causes, the main problem might be the lack of a specific stable and reliable molecular target. In this paper the results obtained using a pentameric amyloid beta (Aβ) model as a molecular target are discussed. Our MD simulations have shown that this system is relatively structured and stable, displaying a lightly conformational flexibility during 2.0 μs of simulation time. This study allowed us to distinguish characteristic structural features in specific regions of the pentamer which should be taken into account when choosing this model as a molecular target. This represents a clear advantage compared to the monomer or dimer models which are highly flexible structures with large numbers of possible conformers. Using this pentameric model we performed two types of studies usually carried out on a molecular target: a virtual screening and the design on structural basis of new mimetic peptides with antiaggregant properties. Our results indicate that this pentameric model might be a good molecular target for these particular studies of molecular modeling. Details about the predictive power of our virtual screening as well as about the molecular interactions that stabilize the mimetic peptide-pentamer Aβ complexes are discussed in this paper.

  19. Design of two-photon molecular tandem architectures for solar cells by ab initio theory

    DEFF Research Database (Denmark)

    Ørnsø, Kristian Baruël; García Lastra, Juan Maria; De La Torre, Gema

    2015-01-01

    An extensive database of spectroscopic properties of molecules from ab initio calculations is used to design molecular complexes for use in tandem solar cells that convert two photons into a single electron–hole pair, thereby increasing the output voltage while covering a wider spectral range...... of the structural and energetic properties of several thousand porphyrin dyes. The third design is a molecular analogy of the intermediate band solar cell, and involves a single dye molecule with strong intersystem crossing to ensure a long lifetime of the intermediate state. Based on the calculated energy levels...... and molecular orbitals, energy diagrams are presented for the individual steps in the operation of such tandem solar cells. We find that theoretical open circuit voltages of up to 1.8 V can be achieved using these tandem designs. Questions about the practical implementation of prototypical devices...

  20. Attachment and psychosis

    NARCIS (Netherlands)

    Korver, N.

    2014-01-01

    The main goal of this thesis was to further our understanding of current psychosocial models by introducing attachment as a relevant developmental framework. Firstly, attachment theory provides a psychosocial model for a developmental pathway to psychosis. Secondly, after expression of psychotic sym

  1. Attachment Theory and Mindfulness

    Science.gov (United States)

    Snyder, Rose; Shapiro, Shauna; Treleaven, David

    2012-01-01

    We initiate a dialog between two central areas in the field of psychology today: attachment theory/research and mindfulness studies. The impact of the early mother-infant relationship on child development has been well established in the literature, with attachment theorists having focused on the correlation between a mother's capacity for…

  2. Temperament and Attachment Disorders

    Science.gov (United States)

    Zeanah, Charles H.; Fox, Nathan A.

    2004-01-01

    Reviewed in this article is research on children with reactive attachment disorder (RAD) who exhibit specific patterns of socially aberrant behavior resulting from being maltreated or having limited opportunities to form selective attachments. There are no data explaining why 2 different patterns of the disorder, an emotionally withdrawn-inhibited…

  3. Reactive Attachment Disorder.

    Science.gov (United States)

    Chapman, Sue

    2002-01-01

    Written by a British parent, this case study tells the story of an adopted child who experienced many difficulties adjusting to life at home and school. It describes attachment disorder, possible causes of attachment difficulties, the bonding cycle, therapeutic parenting, and how schools can support the re-nurturing process. (Contains references.)…

  4. Adolescent attachment and psychopathology.

    Science.gov (United States)

    Rosenstein, D S; Horowitz, H A

    1996-04-01

    The relationships among attachment classification, psychopathology, and personality traits were examined in a group of 60 psychiatrically hospitalized adolescents. The concordance of attachment classification was examined in 27 adolescent-mother pairs. Both adolescent and maternal attachment status were overwhelmingly insecure and were highly concordant. Adolescents showing a dismissing attachment organization were more likely to have a conduct or substance abuse disorder, narcissistic or antisocial personality disorder, and self-reported narcissistic, antisocial, and paranoid personality traits. Adolescents showing a preoccupied attachment organization were more likely to have an affective disorder, obsessive-compulsive, histrionic, borderline or schizotypal personality disorder, and self-reported avoidant, anxious, and dysthymic personality traits. The results support a model of development of psychopathology based partially on relational experiences with parents.

  5. Mechanism study and molecular design in controlled/“living” radical polymerization

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This tutorial review summarizes recent progress in the research field of controlled/"living" radical polymerization (CLRP) from Soochow University.The present paper gives a broad overview of the mechanism study and molecular design in CLRP.The mechanism study in CLRP aided by microwave,initiated by γ-radiation at low temperature,mediated by iron,in reversible addition-fragmentation chain transfer (RAFT) polymerization and the mechanism transfer between different CLRP processes are reviewed and summarized.The molecular design in CLRP,especially in RAFT polymerization for mechanism study,and in achieving tailor-made functional polymers is studied and discussed in the later part.

  6. Development of design information for molecular-sieve type regenerative CO2-removal systems

    Science.gov (United States)

    Wright, R. M.; Ruder, J. M.; Dunn, V. B.; Hwang, K. C.

    1973-01-01

    Experimental and analytic studies were conducted with molecular sieve sorbents to provide basic design information, and to develop a system design technique for regenerable CO2-removal systems for manned spacecraft. Single sorbate equilibrium data were obtained over a wide range of conditions for CO2, water, nitrogen, and oxygen on several molecular sieve and silica gel sorbents. The coadsorption of CO2 with water preloads, and with oxygen and nitrogen was experimentally evaluated. Mass-transfer, and some limited heat-transfer performance evaluations were accomplished under representative operating conditions, including the coadsorption of CO2 and water. CO2-removal system performance prediction capability was derived.

  7. Molecular modeling for the design of novel performance chemicals and materials

    CERN Document Server

    Rai, Beena

    2012-01-01

    Molecular modeling (MM) tools offer significant benefits in the design of industrial chemical plants and material processing operations. While the role of MM in biological fields is well established, in most cases MM works as an accessory in novel products/materials development rather than a tool for direct innovation. As a result, MM engineers and practitioners are often seized with the question: ""How do I leverage these tools to develop novel materials or chemicals in my industry?"" Molecular Modeling for the Design of Novel Performance Chemicals and Materials answers this important questio

  8. Maximizing the dielectric response of molecular thin films via quantum chemical design.

    Science.gov (United States)

    Heitzer, Henry M; Marks, Tobin J; Ratner, Mark A

    2014-12-23

    Developing high-capacitance organic gate dielectrics is critical for advances in electronic circuitry based on unconventional semiconductors. While high-dielectric constant molecular substances are known, the mechanism of dielectric response and the fundamental chemical design principles are not well understood. Using a plane-wave density functional theory formalism, we show that it is possible to map the atomic-scale dielectric profiles of molecule-based materials while capturing important bulk characteristics. For molecular films, this approach reveals how basic materials properties such as surface coverage density, molecular tilt angle, and π-system planarity can dramatically influence dielectric response. Additionally, relatively modest molecular backbone and substituent variations can be employed to substantially enhance film dielectric response. For dense surface coverages and proper molecular alignment, conjugated hydrocarbon chains can achieve dielectric constants of >8.0, more than 3 times that of analogous saturated chains, ∼2.5. However, this conjugation-related dielectric enhancement depends on proper molecular orientation and planarization, with enhancements up to 60% for proper molecular alignment with the applied field and an additional 30% for conformations such as coplanarity in extended π-systems. Conjugation length is not the only determinant of dielectric response, and appended polarizable high-Z substituents can increase molecular film response more than 2-fold, affording estimated capacitances of >9.0 μF/cm2. However, in large π-systems, polar substituent effects are substantially attenuated.

  9. Late-life attachment.

    Science.gov (United States)

    Freitas, Mélanie; Rahioui, Hassan

    2017-03-01

    Old age is likely to cause a crisis in one's life because of the vulnerabilities it brings up, acting as stressful elements disrupting the elder's feeling of security. It leads to the activation of what is called his attachment system, consisting in attachment styles and interpersonal emotional regulation strategies. To recover a higher sense of safety, the elder would refer to his attachment figures, that is to say closed people paying attention to him, showing towards him availability and consideration. However older adults particularly see their tolerance threshold lowered, regarding an accumulation of losses (true or symbolic) and stressful events within their lifetime. In a psychological and organic exhaustion phenomenon, the risk is to wear out the interpersonal emotional regulation strategies. These are as much vulnerabilities that may increase psychiatric decompensation, including depression. To resolve the tension of this period and to found a necessary secure feeling, the elder will have to redesign the attachment links previously settled and proceed to adjustments to this new context. The need of relational closeness comes back in the elders' attachment behaviour, counting on attachment figures not only to help their loneliness or dependency, but essentially to support them in a narcissist and affective way. That is why attachment theory enlightens the late life period, such as the new challenges older adults have to face. Many studies recognize its value in understanding the transition to old age, but without proposing conceptualization. We aim first to focus on attachment conception to say how much it is relevant with elderly, and then to describe specific terms of attachment within this population in order to better understand those patients. To finish, we must think about new therapeutic proposals taking into consideration the attachment perspective for a better understanding of old age transition.

  10. Molecular Thermodynamic Modeling and Design of Microencapsulation Systems for Drug Delivery

    DEFF Research Database (Denmark)

    Abildskov, Jens; O’Connell, John P.

    2011-01-01

    is based on fundamental thermodynamic relations and group contributions to properties of pure species (solvent, active ingredient and polymer) and their mixtures. The method is intended for pharmaceuticals with complex molecular structures, for which limited experimental information is known. Case studies......A systematic design strategy is given for computer-aided design of microparticle drug-delivery systems produced by solvent evaporation. In particular, design of solvents, polymer material, and external phase composition are considered for the case when the active ingredient is known. The procedure...... of solvent design are given....

  11. Dissociative Electron Attachment

    Science.gov (United States)

    Arreola, Esmeralda; Esmeralda Arreola Collaboration; Leigh Hargreaves Collaboration

    Since the pioneering work of Boudiaffa et al., it has been understood that electrons, even with energies near or below the ionization threshold, are capable of initiating strand-breaks in human DNA. This discovery raised important questions for cancer treatments, since sub-ionizing electrons are known to be the most copiously produced secondary product of radiation therapy. But even to date these factors are largely excluded from dosimetry calculations. This lack of inclusion is, at least in part, certainly due to the dearth of fundamental data describing low-energy electron interactions with nucleotide molecules that form the basis of DNA. Understanding of how such slow electrons are able to damage DNA remains incomplete, but the strongly peaked nature of Boudiaffa et al.'s data gives strong hints at resonantly driven collision processes. DNA damage is therefore most likely driven by ``dissociative electron attachment'' (DEA). DEA is a rather complicated process to model due to the coupling of electronic and nuclear degrees of freedom in the molecule. At the California State University Fullerton, we are currently commissioning a new spectrometer to study dissociation channels, reaction rates and orientation effects in DEA collisions between slow electrons and nucleotide molecules. At the meeting we will present design parameters and commissioning data for this new apparatus.

  12. Security of attachment and preschool friendships.

    Science.gov (United States)

    Park, K A; Waters, E

    1989-10-01

    Attachment theory proposes that the quality of the mother-child tie predicts the quality of a child's other close relationships. The purpose of this study was to test whether security of attachment to mother is related to the quality of a preschooler's best friendships. 33 4-year-old and their best friends participated (mean age = 46 months). Attachment Q-set data were collected to score security of mother-child attachment. Security data were used to classify the friend pairs as secure-secure or secure-insecure. Best friend dyads were observed for a 1-hour free-play session. Each pair's behavior was described with the Dyadic Relationships Q-set, a measure designed to describe the behavior of a pair of children. Secure-secure pairs were more harmonious, less controlling, more responsive, and happier than secure-insecure pairs. The results are related to previous work on attachment and social competence.

  13. Attachment-related psychodynamics.

    Science.gov (United States)

    Shaver, Phillip R; Mikulincer, Mario

    2002-09-01

    Because there has been relatively little communication and cross-fertilization between the two major lines of research on adult attachment, one based on coded narrative assessments of defensive processes, the other on simple self-reports of 'attachment style' in close relationships, we here explain and review recent work based on a combination of self-report and other kinds of method, including behavioral observations and unconscious priming techniques. The review indicates that considerable progress has been made in testing central hypotheses derived from attachment theory and in exploring unconscious, psychodynamic processes related to affect-regulation and attachment-system activation. The combination of self-report assessment of attachment style and experimental manipulation of other theoretically pertinent variables allows researchers to test causal hypotheses. We present a model of normative and individual-difference processes related to attachment and identify areas in which further research is needed and likely to be successful. One long-range goal is to create a more complete theory of personality built on attachment theory and other object relations theories.

  14. Environmental and genetic influences on early attachment

    Directory of Open Access Journals (Sweden)

    Gervai Judit

    2009-09-01

    Full Text Available Abstract Attachment theory predicts and subsequent empirical research has amply demonstrated that individual variations in patterns of early attachment behaviour are primarily influenced by differences in sensitive responsiveness of caregivers. However, meta-analyses have shown that parenting behaviour accounts for about one third of the variance in attachment security or disorganisation. The exclusively environmental explanation has been challenged by results demonstrating some, albeit inconclusive, evidence of the effect of infant temperament. In this paper, after reviewing briefly the well-demonstrated familial and wider environmental influences, the evidence is reviewed for genetic and gene-environment interaction effects on developing early attachment relationships. Studies investigating the interaction of genes of monoamine neurotransmission with parenting environment in the course of early relationship development suggest that children's differential susceptibility to the rearing environment depends partly on genetic differences. In addition to the overview of environmental and genetic contributions to infant attachment, and especially to disorganised attachment relevant to mental health issues, the few existing studies of gene-attachment interaction effects on development of childhood behavioural problems are also reviewed. A short account of the most important methodological problems to be overcome in molecular genetic studies of psychological and psychiatric phenotypes is also given. Finally, animal research focusing on brain-structural aspects related to early care and the new, conceptually important direction of studying environmental programming of early development through epigenetic modification of gene functioning is examined in brief.

  15. Computational Design of Intrinsic Molecular Rectifiers Based on Asymmetric Functionalization of N-Phenylbenzamide.

    Science.gov (United States)

    Ding, Wendu; Koepf, Matthieu; Koenigsmann, Christopher; Batra, Arunabh; Venkataraman, Latha; Negre, Christian F A; Brudvig, Gary W; Crabtree, Robert H; Schmuttenmaer, Charles A; Batista, Victor S

    2015-12-01

    We report a systematic computational search of molecular frameworks for intrinsic rectification of electron transport. The screening of molecular rectifiers includes 52 molecules and conformers spanning over 9 series of structural motifs. N-Phenylbenzamide is found to be a promising framework with both suitable conductance and rectification properties. A targeted screening performed on 30 additional derivatives and conformers of N-phenylbenzamide yielded enhanced rectification based on asymmetric functionalization. We demonstrate that electron-donating substituent groups that maintain an asymmetric distribution of charge in the dominant transport channel (e.g., HOMO) enhance rectification by raising the channel closer to the Fermi level. These findings are particularly valuable for the design of molecular assemblies that could ensure directionality of electron transport in a wide range of applications, from molecular electronics to catalytic reactions.

  16. Solution NMR structure of a designed metalloprotein and complementary molecular dynamics refinement.

    Science.gov (United States)

    Calhoun, Jennifer R; Liu, Weixia; Spiegel, Katrin; Dal Peraro, Matteo; Klein, Michael L; Valentine, Kathleen G; Wand, A Joshua; DeGrado, William F

    2008-02-01

    We report the solution NMR structure of a designed dimetal-binding protein, di-Zn(II) DFsc, along with a secondary refinement step employing molecular dynamics techniques. Calculation of the initial NMR structural ensemble by standard methods led to distortions in the metal-ligand geometries at the active site. Unrestrained molecular dynamics using a nonbonded force field for the metal shell, followed by quantum mechanical/molecular mechanical dynamics of DFsc, were used to relax local frustrations at the dimetal site that were apparent in the initial NMR structure and provide a more realistic description of the structure. The MD model is consistent with NMR restraints, and in good agreement with the structural and functional properties expected for DF proteins. This work demonstrates that NMR structures of metalloproteins can be further refined using classical and first-principles molecular dynamics methods in the presence of explicit solvent to provide otherwise unavailable insight into the geometry of the metal center.

  17. A review on molecular topology: applying graph theory to drug discovery and design

    Science.gov (United States)

    Amigó, José María; Gálvez, Jorge; Villar, Vincent M.

    2009-07-01

    Molecular topology is an application of graph theory and statistics in fields like chemistry, biology, and pharmacology, in which the molecular structure matters. Its scope is the topological characterization of molecules by means of numerical invariants, called topological indices, which are the main ingredients of the molecular topological models. These are statistical models that are instrumental in the discovery of new applications of naturally occurring molecules, as well as in the design of synthetic molecules with specific chemical, biological, or pharmacological properties. In this review, we focus on pharmacology, which is a novel field of application of molecular topology. Besides summarizing some recent developments, we also seek to bring closer this interesting biomedical application of mathematics to an interdisciplinary readership.

  18. Molecular docking as a popular tool in drug design, an in silico travel.

    Science.gov (United States)

    de Ruyck, Jerome; Brysbaert, Guillaume; Blossey, Ralf; Lensink, Marc F

    2016-01-01

    New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism-or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein-protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery.

  19. Clinical evaluation of mandibular implant overdentures via Locator implant attachment and Locator bar attachment

    Science.gov (United States)

    Seo, Yong-Ho; Bae, Eun-Bin; Kim, Jung-Woo; Lee, So-Hyoun; Jeong, Chang-Mo; Jeon, Young-Chan

    2016-01-01

    PURPOSE The aim of this study was to evaluate the clinical findings and patient satisfaction on implant overdenture designed with Locator implant attachment or Locator bar attachment in mandibular edentulous patients. MATERIALS AND METHODS Implant survival rate, marginal bone loss, probing depth, peri-implant inflammation, bleeding, plaque, calculus, complications, and satisfaction were evaluated on sixteen patients who were treated with mandibular overdenture and have used it for at least 1 year (Locator implant attachment: n=8, Locator bar attachment: n=8). RESULTS Marginal bone loss, probing depth, plaque index of the Locator bar attachment group were significantly lower than the Locator implant attachment group (P.05). The replacement of the attachment components was the most common complication in both groups. Although there was no correlation between marginal bone loss and plaque index, a significant correlation was found between marginal bone loss and probing depth. CONCLUSION The Locator bar attachment group indicates lesser marginal bone loss and need for maintenance, as compared with the Locator implant attachment group. This may be due to the splinting effect among implants rather than the types of Locator attachment. PMID:27555901

  20. Giant Atomic and Molecular Models and Other Lecture Demonstration Devices Designed for Concrete Operational Students.

    Science.gov (United States)

    Battino, Rubin

    1983-01-01

    Describes the design, construction, and use of oversize lecture-demonstration atomic/molecular models. These models appeal to both concrete and formal operational students. Also describes construction and use of an "spdf" sandwich board and an experiment using attribute blocks. (JN)

  1. Molecular Docking of Enzyme Inhibitors: A Computational Tool for Structure-Based Drug Design

    Science.gov (United States)

    Rudnitskaya, Aleksandra; Torok, Bela; Torok, Marianna

    2010-01-01

    Molecular docking is a frequently used method in structure-based rational drug design. It is used for evaluating the complex formation of small ligands with large biomolecules, predicting the strength of the bonding forces and finding the best geometrical arrangements. The major goal of this advanced undergraduate biochemistry laboratory exercise…

  2. Aggression And Attachment Security

    Directory of Open Access Journals (Sweden)

    Prem Verma

    2007-06-01

    Full Text Available Objective:The aim of the present study is to examine the factors related aggression in Iranian and Indian school children. Method: Attachment security (dependency, availability, and total considered as the variable. The KSS questionnaire was administrated students in the 5th grade; 300 were Iranian and 300 were Indian consisted of 150 boys and 150 girls. Results: Attachment security demonstrated significant negative correlations with aggression in the boys, girls and the total Iranian sample. The dependency on mothers was the only case with insignificant correlation.In the Indian sample, attachment security was also found to be significantly negatively correlated with aggression. The only exception was the correlation between mother's availability and aggression in girls, which was not significant Conclusion: It is important that parents treat their children in a tender, manner so that a secure attachment develop between them.

  3. Attachment to land

    Directory of Open Access Journals (Sweden)

    Paul Rozin

    2008-04-01

    Full Text Available This is a first study on attachment to national and sacred land and land as a protected value. A measure of attachment to the land of Israel is developed and administered to two groups, Jewish college students in Israel and the United States. Levels of land attachment are high and not significantly different in the two groups, with a great deal of variation. Land may become more important through being inhabited by a group over centuries. This is a positive contagion effect, and is opposed in some cases by negative contagion produced when the ``enemies'' live on the land for some period of time. We demonstrate a significant correlation of positive contagion sensitivity with attachment to the land of Israel. Unlike many other cases of the interaction of positive and negative contagion, negative contagion does not overwhelm positive contagion in the domain of land attachment. We also present evidence for linkages between political positions, religiosity, importance of Israel, Arab aversion, and vulnerability of Israel with attachment to land, but these do not fully account for the contagion effects. A number of significant differences between Israelis and Americans are described.

  4. Computer-Aided Molecular Design of Bis-phosphine Oxide Lanthanide Extractants.

    Science.gov (United States)

    McCann, Billy W; Silva, Nuwan De; Windus, Theresa L; Gordon, Mark S; Moyer, Bruce A; Bryantsev, Vyacheslav S; Hay, Benjamin P

    2016-06-20

    Computer-aided molecular design and high-throughput screening of viable host architectures can significantly reduce the efforts in the design of novel ligands for efficient extraction of rare earth elements. This paper presents a computational approach to the deliberate design of bis-phosphine oxide host architectures that are structurally organized for complexation of trivalent lanthanides. Molecule building software, HostDesigner, was interfaced with molecular mechanics software, PCModel, providing a tool for generating and screening millions of potential R2(O)P-link-P(O)R2 ligand geometries. The molecular mechanics ranking of ligand structures is consistent with both the solution-phase free energies of complexation obtained with density functional theory and the performance of known bis-phosphine oxide extractants. For the case where the link is -CH2-, evaluation of the ligand geometry provides the first characterization of a steric origin for the "anomalous aryl strengthening" effect. The design approach has identified a number of novel bis-phosphine oxide ligands that are better organized for lanthanide complexation than previously studied examples.

  5. Design Molecular Recognition Materials for Chiral Sensors, Separtations and Catalytic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Jia, S.; Nenoff, T.M.; Provencio, P.; Qiu, Y.; Shelnutt, J.A.; Thoma, S.G.; Zhang, J.

    1998-11-01

    The goal is the development of materials that are highly sensitive and selective for chid chemicals and biochemical (such as insecticides, herbicides, proteins, and nerve agents) to be used as sensors, catalysts and separations membranes. Molecular modeling methods are being used to tailor chiral molecular recognition sites with high affinity and selectivity for specified agents. The work focuses on both silicate and non-silicate materials modified with chirally-pure fictional groups for the catalysis or separations of enantiomerically-pure molecules. Surfactant and quaternary amine templating is being used to synthesize porous frameworks, containing mesopores of 30 to 100 angstroms. Computer molecukw modeling methods are being used in the design of these materials, especially in the chid surface- modi~ing agents. Molecular modeling is also being used to predict the catalytic and separations selectivities of the modified mesoporous materials. The ability to design and synthesize tailored asymmetric molecular recognition sites for sensor coatings allows a broader range of chemicals to be sensed with the desired high sensitivity and selectivity. Initial experiments target the selective sensing of small molecule gases and non-toxic model neural compounds. Further efforts will address designing sensors that greatly extend the variety of resolvable chemical species and forming a predictive, model-based method for developing advanced sensors.

  6. Crystal growth inhibitors for the prevention of L-cystine kidney stones through molecular design.

    Science.gov (United States)

    Rimer, Jeffrey D; An, Zhihua; Zhu, Zina; Lee, Michael H; Goldfarb, David S; Wesson, Jeffrey A; Ward, Michael D

    2010-10-15

    Crystallization of L-cystine is a critical step in the pathogenesis of cystine kidney stones. Treatments for this disease are somewhat effective but often lead to adverse side effects. Real-time in situ atomic force microscopy (AFM) reveals that L-cystine dimethylester (L-CDME) and L-cystine methylester (L-CME) dramatically reduce the growth velocity of the six symmetry-equivalent {100} steps because of specific binding at the crystal surface, which frustrates the attachment of L-cystine molecules. L-CDME and L-CME produce l-cystine crystals with different habits that reveal distinct binding modes at the crystal surfaces. The AFM observations are mirrored by reduced crystal yield and crystal size in the presence of L-CDME and L-CME, collectively suggesting a new pathway to the prevention of L-cystine stones by rational design of crystal growth inhibitors.

  7. Crystal Growth Inhibitors for the Prevention of L-Cystine Kidney Stones Through Molecular Design

    Energy Technology Data Exchange (ETDEWEB)

    Rimer, Jeffrey D.; An, Zhihua; Zhu, Zina; Lee, Michael H.; Goldfarb, David S.; Wesson, Jeffrey A.; Ward, Michael D. (NY Univ.); (MCW)

    2010-11-12

    Crystallization of L-cystine is a critical step in the pathogenesis of cystine kidney stones. Treatments for this disease are somewhat effective but often lead to adverse side effects. Real-time in situ atomic force microscopy (AFM) reveals that L-cystine dimethylester (L-CDME) and L-cystine methylester (L-CME) dramatically reduce the growth velocity of the six symmetry-equivalent {l_brace}100{r_brace} steps because of specific binding at the crystal surface, which frustrates the attachment of L-cystine molecules. L-CDME and L-CME produce L-cystine crystals with different habits that reveal distinct binding modes at the crystal surfaces. The AFM observations are mirrored by reduced crystal yield and crystal size in the presence of L-CDME and L-CME, collectively suggesting a new pathway to the prevention of L-cystine stones by rational design of crystal growth inhibitors.

  8. Design and synthesis of new biprivileged molecular scaffolds: indolo-fused benzodiazepinyl/quinoxalinyl benzimidazoles.

    Science.gov (United States)

    Barve, Indrajeet J; Chen, Chan-Yu; Salunke, Deepak B; Chung, Wen-Sheng; Sun, Chung-Ming

    2012-06-01

    The present article describes the design and synthesis of new biprivileged molecular scaffolds with diverse structural features. Commercially available, simple heterocyclic building blocks such as 4-fluoro-3-nitrobenzoic acid, 2-chloro-3-nitrobenzoic acid, and indoline were utilized for the synthesis of the novel heterocycles. Pictet-Spengler-type condensation was used as a key step to construct tetracyclic indolo-benzodiazepines and indolo-quinoxalines linked with substituted benzimidazoles. Analysis of single crystals of representative compounds showed that these molecular skeletons have the potential to present various substituents with distinct three-dimensional orientations.

  9. Molecular Model Design and Quantum Chemistry Calculation of Cluster B4N4

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The B4N4 configurations were designed by using the molecular figure software. The full geometry optimization and harmonic vibration frequency analysis were performed at the 6-31G(d) level using density functional theory B3LYP method, which indicates that the five isomers are stationary points on the potential energy surface of B4N4 molecules. The geometry structure, frontier molecular orbital (FMO) and mulliken population have been analyzed. The bonding properties and hybrid type were also discussed in detail, showing the addition of hydro- gen atoms to boron or nitrogen atom would increase the stabilities of the BN clusters.

  10. Design of protein-ligand binding based on the molecular-mechanics energy model.

    Science.gov (United States)

    Boas, F Edward; Harbury, Pehr B

    2008-07-04

    While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can be used to engineer protein-ligand binding. A molecular-mechanics potential is used to reconstruct the coordinates of various binding sites with an average root-mean-square error of 0.61 A and to reproduce known ligand-induced side-chain conformational shifts. Within a series of 34 mutants, the calculation can always distinguish between weak (K(d)>1 mM) and tight (K(d)mechanics potential is used to redesign a ribose-binding site. Out of a search space of 2 x 10(12) sequences, the calculation selects a point mutant of the native protein as the top solution (experimental K(d)=17 microM) and the native protein as the second best solution (experimental K(d)=210 nM). The quality of the predictions depends on the accuracy of the generalized Born electrostatics model, treatment of protonation equilibria, high-resolution rotamer sampling, a final local energy minimization step, and explicit modeling of the bound, unbound, and unfolded states. The application of unmodified molecular-mechanics potentials to protein design links two fields in a mutually beneficial way. Design provides a new avenue for testing molecular-mechanics energy functions, and future improvements in these energy functions will presumably lead to more accurate design results.

  11. Structure-based de novo design, molecular docking and molecular dynamics of primaquine analogues acting as quinone reductase II inhibitors.

    Science.gov (United States)

    Murce, Erika; Cuya-Guizado, Teobaldo Ricardo; Padilla-Chavarria, Helmut Isaac; França, Tanos Celmar Costa; Pimentel, Andre Silva

    2015-11-01

    Primaquine is a traditional antimalarial drug with low parasitic resistance and generally good acceptance at higher doses, which has been used for over 60 years in malaria treatment. However, several limitations related to its hematotoxicity have been reported. It is believed that this toxicity comes from the hydroxylation of the C-5 and C-6 positions of its 8-aminoquinoline ring before binding to the molecular target: the quinone reductase II (NQO2) human protein. In this study we propose primaquine derivatives, with substitution at position C-6 of the 8-aminoquinoline ring, planned to have better binding to NQO2, compared to primaquine, but with a reduced toxicity related to the C-5 position being possible to be oxidized. On this sense the proposed analogues were suggested in order to reduce or inhibit hydroxylation and further oxidation to hemotoxic metabolites. Five C-6 substituted primaquine analogues were selected by de novo design and further submitted to docking and molecular dynamics simulations. Our results suggest that all analogues bind better to NQO2 than primaquine and may become better antimalarials. However, the analogues 3 and 4 are predicted to have a better activity/toxicity balance.

  12. Nucleotide and Predicted Amino Acid Sequence-Based Analysis of the Avian Metapneumovirus Type C Cell Attachment Glycoprotein Gene: Phylogenetic Analysis and Molecular Epidemiology of U.S. Pneumoviruses

    Science.gov (United States)

    Alvarez, Rene; Lwamba, Humphrey M.; Kapczynski, Darrell R.; Njenga, M. Kariuki; Seal, Bruce S.

    2003-01-01

    A serologically distinct avian metapneumovirus (aMPV) was isolated in the United States after an outbreak of turkey rhinotracheitis (TRT) in February 1997. The newly recognized U.S. virus was subsequently demonstrated to be genetically distinct from European subtypes and was designated aMPV serotype C (aMPV/C). We have determined the nucleotide sequence of the gene encoding the cell attachment glycoprotein (G) of aMPV/C (Colorado strain and three Minnesota isolates) and predicted amino acid sequence by sequencing cloned cDNAs synthesized from intracellular RNA of aMPV/C-infected cells. The nucleotide sequence comprised 1,321 nucleotides with only one predicted open reading frame encoding a protein of 435 amino acids, with a predicted Mr of 48,840. The structural characteristics of the predicted G protein of aMPV/C were similar to those of the human respiratory syncytial virus (hRSV) attachment G protein, including two mucin-like regions (heparin-binding domains) flanking both sides of a CX3C chemokine motif present in a conserved hydrophobic pocket. Comparison of the deduced G-protein amino acid sequence of aMPV/C with those of aMPV serotypes A, B, and D, as well as hRSV revealed overall predicted amino acid sequence identities ranging from 4 to 16.5%, suggesting a distant relationship. However, G-protein sequence identities ranged from 72 to 97% when aMPV/C was compared to other members within the aMPV/C subtype or 21% for the recently identified human MPV (hMPV) G protein. Ratios of nonsynonymous to synonymous nucleotide changes were greater than one in the G gene when comparing the more recent Minnesota isolates to the original Colorado isolate. Epidemiologically, this indicates positive selection among U.S. isolates since the first outbreak of TRT in the United States. PMID:12682171

  13. Role of aromatic rings in the molecular recognition of aminoglycoside antibiotics: implications for drug design.

    Science.gov (United States)

    Vacas, Tatiana; Corzana, Francisco; Jiménez-Osés, Gonzalo; González, Carlos; Gómez, Ana M; Bastida, Agatha; Revuelta, Julia; Asensio, Juan Luis

    2010-09-01

    Aminoglycoside antibiotics participate in a large variety of binding processes involving both RNA and proteins. The description, in recent years, of several clinically relevant aminoglycoside/receptor complexes has greatly stimulated the structural-based design of new bioactive derivatives. Unfortunately, design efforts have frequently met with limited success, reflecting our incomplete understanding of the molecular determinants for the antibiotic recognition. Intriguingly, aromatic rings of the protein/RNA receptors seem to be key actors in this process. Indeed, close inspection of the structural information available reveals that they are frequently involved in CH/pi stacking interactions with sugar/aminocyclitol rings of the antibiotic. While the interaction between neutral carbohydrates and aromatic rings has been studied in detail during past decade, little is known about these contacts when they involve densely charged glycosides. Herein we report a detailed experimental and theoretical analysis of the role played by CH/pi stacking interactions in the molecular recognition of aminoglycosides. Our study aims to determine the influence that the antibiotic polycationic character has on the stability, preferred geometry, and dynamics of these particular contacts. With this purpose, different aminoglycoside/aromatic complexes have been selected as model systems. They varied from simple bimolecular interactions to the more stable intramolecular CH/pi contacts present in designed derivatives. The obtained results highlight the key role played by electrostatic forces and the desolvation of charged groups in the molecular recognition of polycationic glycosides and have clear implications for the design of improved antibiotics.

  14. Reducing aquatic hazards of industrial chemicals: probabilistic assessment of sustainable molecular design guidelines.

    Science.gov (United States)

    Connors, Kristin A; Voutchkova-Kostal, Adelina M; Kostal, Jakub; Anastas, Paul; Zimmerman, Julie B; Brooks, Bryan W

    2014-08-01

    Basic toxicological information is lacking for the majority of industrial chemicals. In addition to increasing empirical toxicity data through additional testing, prospective computational approaches to drug development aim to serve as a rational basis for the design of chemicals with reduced toxicity. Recent work has resulted in the derivation of a "rule of 2," wherein chemicals with an octanol-water partition coefficient (log P) less than 2 and a difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital (ΔE) greater than 9 (log P9 eV) are predicted to be 4 to 5 times less likely to elicit acute or chronic toxicity to model aquatic organisms. The present study examines potential reduction of aquatic toxicity hazards from industrial chemicals if these 2 molecular design guidelines were employed. Probabilistic hazard assessment approaches were used to model the likelihood of encountering industrial chemicals exceeding toxicological categories of concern both with and without the rule of 2. Modeling predicted that utilization of these molecular design guidelines for log P and ΔE would appreciably decrease the number of chemicals that would be designated to be of "high" and "very high" concern for acute and chronic toxicity to standard model aquatic organisms and end points as defined by the US Environmental Protection Agency. For example, 14.5% of chemicals were categorized as having high and very high acute toxicity to the fathead minnow model, whereas only 3.3% of chemicals conforming to the design guidelines were predicted to be in these categories. Considerations of specific chemical classes (e.g., aldehydes), chemical attributes (e.g., ionization), and adverse outcome pathways in representative species (e.g., receptor-mediated responses) could be used to derive future property guidelines for broader classes of contaminants.

  15. Attachment and coercive sexual behavior.

    Science.gov (United States)

    Smallbone, S W; Dadds, M R

    2000-01-01

    This study examined the relationships between childhood attachment and coercive sexual behavior. One hundred sixty-two male undergraduate students completed self-report measures of childhood maternal attachment, childhood paternal attachment, adult attachment, antisociality, aggression, and coercive sexual behavior. As predicted, insecure childhood attachment, especially insecure paternal attachment, was associated with antisociality, aggression, and coercive sexual behavior. Moreover, childhood attachment independently predicted coercive sexual behavior after antisociality and aggression were statistically controlled. The hypothesis that paternal avoidant attachment would predict coercive sexual behavior independently of its relationship with aggression and antisociality was also supported. Posthoc analysis indicated that maternal anxious attachment was associated with antisociality and that paternal avoidant attachment was associated with both antisociality and coercive sexual behavior. These results are consistent with criminological and psychological research linking adverse early family experiences with offending and lend support to an attachment-theoretical framework for understanding offending behavior in general and sexual offending behavior in particular.

  16. A new decomposition-based computer-aided molecular/mixture design methodology for the design of optimal solvents and solvent mixtures

    DEFF Research Database (Denmark)

    Karunanithi, A.T.; Achenie, L.E.K.; Gani, Rafiqul

    2005-01-01

    This paper presents a novel computer-aided molecular/mixture design (CAMD) methodology for the design of optimal solvents and solvent mixtures. The molecular/mixture design problem is formulated as a mixed integer nonlinear programming (MINLP) model in which a performance objective...... is to be optimized subject to structural, property, and process constraints. The general molecular/mixture design problem is divided into two parts. For optimal single-compound design, the first part is solved. For mixture design, the single-compound design is first carried out to identify candidates...... the design of an optimal extractant for the separation of acetic acid from water by liquid-liquid extraction. The results suggest that the new extractant would be able to perform better than the extractant being widely used for this separation. The second case study is an industrial problem involving...

  17. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 3, Groundwater hydrology report. Revised final report

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-01

    The US Environmental Protection Agency (EPA) has established health and environmental protection regulations to correct and prevent groundwater contamination resulting from processing activities at inactive uranium milling sites. According to the Uranium Mill Tailings Radiation Control Act of 1978, (UMTRCA) the US Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has determined this assessment shall include information on hydrogeologic site characterization. The water resources protection strategy that describes how the proposed action will comply with the EPA groundwater protection standards is presented in Attachment 4. Site characterization activities discussed in this section include: Characterization of the hydrogeologic environment; characterization of existing groundwater quality; definition of physical and chemical characteristics of the potential contaminant source; and description of local water resources.

  18. Pain, Affect, and Attachment

    Directory of Open Access Journals (Sweden)

    Carl Eduard Scheidt

    2015-03-01

    Full Text Available Various psychodynamic processes may underlie the development of psychogenic pain disorder such as conversion, the displacement of affect, or narcissistic defenses. However, many of the processes suggested are related to a disorder of affect regulation. The term affect regulation in psychoanalytic literature refers to phenomena which are often described by the concept of alexithymia. Empirical observations suggest that alexithymia is correlated to insecure attachment, especially an insecure dismissing representation of attachment. Psychodynamic psychotherapy in psychogenic pain disorder should focus on the reintegration of split-off affects which may provoke intensive counter-transference and which in order to be used therapeutically must be linked to attachment experiences within and outside of the therapeutic relationship.

  19. Love attitudes and attachment

    Directory of Open Access Journals (Sweden)

    María Elena Brenlla

    2016-02-01

    Full Text Available Love styles described by Lee are Eros (passionate love, Ludus (game-pla- ying love, Storge (friendship love, Mania (possessive, dependent love, Pragma (logical, “shopping list” love and Agape (all-giving, selfless love. Based on those types, Hendrick and Hendrick developed a 42-ítem rating questionnaire with 7 items measuring each love style (Love Attitudes Scale. Beside, inform about frequency in love relationships and attachment style. The purpose of this study was analyze the reliability and factor structure of the Love Attitudes Scale and to investigate the association between love attitudes and the attachment style. The results (N=280 participants indicate adequate internal consistency (alfa = 0,73. The items were intercorrelated and factored. The best solution extracted six factors using varimax rotation and all six factors accounted 41% of the total variance. Secure attachment was related positively to eros. 

  20. Molecular design toward highly efficient photovoltaic polymers based on two-dimensional conjugated benzodithiophene.

    Science.gov (United States)

    Ye, Long; Zhang, Shaoqing; Huo, Lijun; Zhang, Maojie; Hou, Jianhui

    2014-05-20

    As researchers continue to develop new organic materials for solar cells, benzo[1,2-b:4,5-b']dithiophene (BDT)-based polymers have come to the fore. To improve the photovoltaic properties of BDT-based polymers, researchers have developed and applied various strategies leading to the successful molecular design of highly efficient photovoltaic polymers. Novel polymer materials composed of two-dimensional conjugated BDT (2D-conjugated BDT) have boosted the power conversion efficiency of polymer solar cells (PSCs) to levels that exceed 9%. In this Account, we summarize recent progress related to the design and synthesis of 2D-conjugated BDT-based polymers and discuss their applications in highly efficient photovoltaic devices. We introduce the basic considerations for the construction of 2D-conjugated BDT-based polymers and systematic molecular design guidelines. For example, simply modifying an alkoxyl-substituted BDT to form an alkylthienyl-substituted BDT can improve the polymer hole mobilities substantially with little effect on their molecular energy level. Secondly, the addition of a variety of chemical moieties to the polymer can produce a 2D-conjugated BDT unit with more functions. For example, the introduction of a conjugated side chain with electron deficient groups (such as para-alkyl-phenyl, meta-alkoxyl-phenyl, and 2-alkyl-3-fluoro-thienyl) allowed us to modulate the molecular energy levels of 2D-conjugated BDT-based polymers. Through the rational design of BDT analogues such as dithienobenzodithiophene (DTBDT) or the insertion of larger π bridges, we can tune the backbone conformations of these polymers and modulate their photovoltaic properties. We also discuss the influence of 2D-conjugated BDT on polymer morphology and the blends of these polymers with phenyl-C61 (or C71)-butyric acid methyl ester (PCBM). Finally, we summarize the various applications of the 2D-conjugated BDT-based polymers in highly efficient PSC devices. Overall, this Account

  1. Design and Construction of a One-Dimensional DNA Track for an Artificial Molecular Motor

    Directory of Open Access Journals (Sweden)

    Suzana Kovacic

    2012-01-01

    Full Text Available DNA is a versatile heteropolymer that shows great potential as a building block for a diverse array of nanostructures. We present here a solution to the problem of designing and synthesizing a DNA-based nanostructure that will serve as the track along which an artificial molecular motor processes. This one-dimensional DNA track exhibits periodically repeating elements that provide specific binding sites for the molecular motor. Besides these binding elements, additional sequences are necessary to label specific regions within the DNA track and to facilitate track construction. Designing an ideal DNA track sequence presents a particular challenge because of the many variable elements that greatly expand the number of potential sequences from which the ideal sequence must be chosen. In order to find a suitable DNA sequence, we have adapted a genetic algorithm which is well suited for a large but sparse search space. This algorithm readily identifies long DNA sequences that include all the necessary elements to both facilitate DNA track construction and to present appropriate binding sites for the molecular motor. We have successfully experimentally incorporated the sequence identified by the algorithm into a long DNA track meeting the criteria for observation of the molecular motor's activity.

  2. Strategies to design pyrazolyl urea derivatives for p38 kinase inhibition: a molecular modeling study

    Science.gov (United States)

    Kulkarni, Ravindra G.; Srivani, Palukuri; Achaiah, Garlapati; Sastry, G. Narahari

    2007-04-01

    The p38 protein kinase is a serine-threonine mitogen activated protein kinase, which plays an important role in inflammation and arthritis. A combined study of 3D-QSAR and molecular docking has been undertaken to explore the structural insights of pyrazolyl urea p38 kinase inhibitors. The 3D-QSAR studies involved comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The best CoMFA model was derived from the atom fit alignment with a cross-validated r 2 ( q 2) value of 0.516 and conventional r 2 of 0.950, while the best CoMSIA model yielded a q 2 of 0.455 and r 2 of 0.979 (39 molecules in training set, 9 molecules in test set). The CoMFA and CoMSIA contour maps generated from these models provided inklings about the influence of interactive molecular fields in the space on the activity. GOLD, Sybyl (FlexX) and AutoDock docking protocols were exercised to explore the protein-inhibitor interactions. The integration of 3D-QSAR and molecular docking has proffered essential structural features of pyrazolyl urea inhibitors and also strategies to design new potent analogues with enhanced activity.

  3. Rationale and design of the Japan molecular epidemiology for lung cancer study.

    Science.gov (United States)

    Kawaguchi, Tomoya; Ando, Masahiko; Ito, Norimasa; Isa, Shun-Ichi; Tamiya, Akihiro; Shimizu, Shigeki; Saka, Hideo; Kubo, Akihito; Koh, Yasuhiro; Matsumura, Akihide

    2013-09-01

    We present the rationale for the Japan Molecular Epidemiology for Lung Cancer study designed to elucidate molecular mechanisms of carcinogenesis in smokers and never-smokers with non-small-cell lung cancer. This prospective, ongoing, multicenter study is being conducted nationwide in Japan. Although there is no doubt that active smoking is the major cause of lung cancer, the contribution of other possible factors, including environmental tobacco or wood smoke, human papilloma virus, radon, occupational exposures, and genetic susceptibility, is highly likely, based on studies of never-smokers with non-small-cell lung cancer. Because of the predominance of women in the never-smoker subgroup, the role of female hormones in lung cancer development has also been considered. We hypothesize that driver mutations, which are critical for the development of lung cancer, are triggered by the environmental factors with or without the influence of the hormone. The SWOG-led intergroup molecular epidemiology study S0424 was conducted to focus on these issues by using a detailed questionnaire and specimen collection in statistically significant cohorts of smokers and never-smokers from both sexes. The Japan Molecular Epidemiology for Lung Cancer study follows and extends the S0424 molecular epidemiology concept in principle by using a similar approach that will facilitate future comparisons between the studies but with a greater focus on more recently defined driver mutations and broad genomic sequencing.

  4. Liquid-Phase Exfoliation of Phosphorene: Design Rules from Molecular Dynamics Simulations.

    Science.gov (United States)

    Sresht, Vishnu; Pádua, Agílio A H; Blankschtein, Daniel

    2015-08-25

    The liquid-phase exfoliation of phosphorene, the two-dimensional derivative of black phosphorus, in the solvents dimethyl sulfoxide (DMSO), dimethylformamide (DMF), isopropyl alcohol, N-methyl-2-pyrrolidone, and N-cyclohexyl-2-pyrrolidone is investigated using three molecular-scale "computer experiments". We modeled solvent-phosphorene interactions using an atomistic force field, based on ab initio calculations and lattice dynamics, that accurately reproduces experimental mechanical properties. We probed solvent molecule ordering at phosphorene/solvent interfaces and discovered that planar molecules such as N-methyl-2-pyrrolidone preferentially orient parallel to the interface. We subsequently measured the energy required to peel a single phosphorene monolayer from a stack of black phosphorus and analyzed the role of "wedges" of solvent molecules intercalating between phosphorene sheets in initiating exfoliation. The exfoliation efficacy of a solvent is enhanced when either molecular planarity "sharpens" this molecular wedge or strong phosphorene-solvent adhesion stabilizes the newly exposed phosphorene surfaces. Finally, we examined the colloidal stability of exfoliated flakes by simulating their aggregation and showed that dispersion is favored when the cohesive energy between the molecules in the solvent monolayer confined between the phosphorene sheets is high (as with DMSO) and is hindered when the adhesion between these molecules and phosphorene is strong; the molecular planarity in solvents like DMF enhances the cohesive energy. Our results are consistent with, and provide a molecular context for, experimental exfoliation studies of phosphorene and other layered solids, and our molecular insights into the significant role of solvent molecular geometry and ordering should complement prevalent solubility-parameter-based approaches in establishing design rules for effective nanomaterial exfoliation media.

  5. Attachment Theory in Tourism

    OpenAIRE

    Korstanje, Maximiliano

    2007-01-01

    The following work is intended to a revision on attachment theory. The postulates of the theory of the sure base point that the system of exploration meets in narrow relation the system of conducts of attachment and the figure of the keepers. The conducts that characterize and symbolize the relation of the adult with the environment are carried back to the early age, in the moment in which the child develops the affective capacity. What difference does exist between someone who decides to jou...

  6. Ladder attachment platform

    Science.gov (United States)

    Swygert,; Richard, W [Springfield, SC

    2012-08-28

    A ladder attachment platform is provided that includes a base for attachment to a ladder that has first and second side rails and a plurality of rungs that extend between in a lateral direction. Also included is a user platform for having a user stand thereon that is carried by the base. The user platform may be positioned with respect to the ladder so that it is not located between a first plane that extends through the first side rail and is perpendicular to the lateral direction and a second plane that extends through the second side rail and is perpendicular to the lateral direction.

  7. Molecular Design and Evaluation of Biodegradable Polymers Using a Statistical Approach

    OpenAIRE

    Lewitus, Dan; Rios, Fabian; Rojas, Ramiro; Kohn, Joachim

    2013-01-01

    The challenging paradigm of bioresorbable polymers, whether in drug delivery or tissue engineering, states that a fine-tuning of the interplay between polymer properties (e.g., thermal, degradation), and the degree of cell/tissue replacement and remodeling is required. In this paper we describe how changes in the molecular architecture of a series of terpolymers allow for the design of polymers with varying glass transition temperatures and degradation rates. The effect of each component in t...

  8. Molecular design of seed storage proteins for enhanced food physicochemical properties.

    Science.gov (United States)

    Tandang-Silvas, Mary Rose G; Tecson-Mendoza, Evelyn Mae; Mikami, Bunzo; Utsumi, Shigeru; Maruyama, Nobuyuki

    2011-01-01

    Seed storage proteins such as soybean globulins have been nutritionally and functionally valuable in the food industry. Protein structure-function studies are valuable in modifying proteins for enhanced functionality. Recombinant technology and protein engineering are two of the tools in biotechnology that have been used in producing soybean proteins with better gelling property, solubility, and emulsifying ability. This article reviews the molecular basis for the logical and precise protein designs that are important in obtaining the desired improved physicochemical properties.

  9. A New Optimization Model for Computer-Aided Molecular Design Problems

    DEFF Research Database (Denmark)

    Zhang, Lei; Cignitti, Stefano; Gani, Rafiqul

    as known molecules with desired properties. The attention is in particular targeted at the design of chemical based products, such as solvents, refrigerants, active pharmaceutical ingredients, polymers, surfactants, lubricants, and more [1]. Property prediction methods are needed in molecular design...... to be determined. In this way, CAMD problems can be formulated as a Mixed Integer Linear/Non-Linear Program (MILP/MINLP). With the advent of connectivity-based prediction methods, several researchers have developed new strategies for embedding it with CAMD method. Constantinou et al. [2] proposed a systematic...

  10. Attachment and Women's Faith Development

    Science.gov (United States)

    Joung, Eun Sim

    2006-01-01

    This article explores the relationship between human attachment and God attachment, particularly in Christian women's experiences of faith. It is based on the attachment perspective as a conceptual framework. The main aim was to evolve an attachment-theoretical approach to women's faith development and to offer a complementary path to interpret…

  11. Impact of Binding Site Comparisons on Medicinal Chemistry and Rational Molecular Design.

    Science.gov (United States)

    Ehrt, Christiane; Brinkjost, Tobias; Koch, Oliver

    2016-05-12

    Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct selectivity patterns and the prediction of possible off-target effects. The identification of similarities between binding sites of various proteins is a useful approach to cope with those challenges. The main scope of this perspective is to describe applications of different protein binding site comparison approaches to outline their applicability and impact on molecular design. The article deals with various substantial application domains and provides some outstanding examples to show how various binding site comparison methods can be applied to promote in silico drug design workflows. In addition, we will also briefly introduce the fundamental principles of different protein binding site comparison methods.

  12. Interactive Multimodal Molecular Set – Designing Ludic Engaging Science Learning Content

    DEFF Research Database (Denmark)

    Thorsen, Tine Pinholt; Christiansen, Kasper Holm Bonde; Jakobsen Sillesen, Kristian;

    2014-01-01

    This paper reports on an exploratory study investigating 10 primary school students’ interaction with an interactive multimodal molecular set fostering ludic engaging science learning content in primary schools (8th and 9th grade). The concept of the prototype design was to bridge the physical...... and virtual worlds with electronic tags and, through this, blend the familiarity of the computer and toys, to create a tool that provided a ludic approach to learning about atoms and molecules. The study was inspired by the participatory design and informant design methodologies and included design...... collaboratorium sessions, interviews and observations. The results indicated that bridging the physical and digital worlds can support learning where the affordances of the technologies can be described in terms of meaningful activity: exploration, reasoning, reflection, and ludic engagement. Here, the electronic...

  13. Mechanical-Kinetic Modeling of a Molecular Walker from a Modular Design Principle

    Science.gov (United States)

    Hou, Ruizheng; Loh, Iong Ying; Li, Hongrong; Wang, Zhisong

    2017-02-01

    Artificial molecular walkers beyond burnt-bridge designs are complex nanomachines that potentially replicate biological walkers in mechanisms and functionalities. Improving the man-made walkers up to performance for widespread applications remains difficult, largely because their biomimetic design principles involve entangled kinetic and mechanical effects to complicate the link between a walker's construction and ultimate performance. Here, a synergic mechanical-kinetic model is developed for a recently reported DNA bipedal walker, which is based on a modular design principle, potentially enabling many directional walkers driven by a length-switching engine. The model reproduces the experimental data of the walker, and identifies its performance-limiting factors. The model also captures features common to the underlying design principle, including counterintuitive performance-construction relations that are explained by detailed balance, entropy production, and bias cancellation. While indicating a low directional fidelity for the present walker, the model suggests the possibility of improving the fidelity above 90% by a more powerful engine, which may be an improved version of the present engine or an entirely new engine motif, thanks to the flexible design principle. The model is readily adaptable to aid these experimental developments towards high-performance molecular walkers.

  14. Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands.

    Science.gov (United States)

    Vettoretti, Gerolamo; Moroni, Elisabetta; Sattin, Sara; Tao, Jiahui; Agard, David A; Bernardi, Anna; Colombo, Giorgio

    2016-04-01

    Controlling biochemical pathways through chemically designed modulators may provide novel opportunities to develop therapeutic drugs and chemical tools. The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target protein. We examine the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics (MD) simulations and analysis of protein-ligand interactions. In particular, we focus on the cross-talk between allosteric ligands and protein conformations and its effect on the dynamic properties of the chaperone's active state. We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state. A critical aspect of this study is the development of a quantitative model that correlates Hsp90 activation to the presence of a certain compound, making use of information on the dynamic adaptation of protein conformations to the presence of the ligand, which allows to capture conformational states relevant in the activation process. We discuss the implications of considering the conformational dialogue between allosteric ligands and protein conformations for the design of new functional modulators.

  15. Molecular docking as a popular tool in drug design, an in silico travel

    Directory of Open Access Journals (Sweden)

    de Ruyck J

    2016-06-01

    Full Text Available Jerome de Ruyck, Guillaume Brysbaert, Ralf Blossey, Marc F Lensink University Lille, CNRS UMR8576 UGSF, Lille, FranceAbstract: New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism- or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein–protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery.Keywords: structure-based drug design, protein–protein docking, quaternary structure prediction, residue interaction networks, RINs, water position

  16. Personality disorders, attachment and psychodynamic psychotherapy.

    Science.gov (United States)

    Weinstein, Lissa; Perez-Rodriguez, M Mercedes; Siever, Larry

    2014-01-01

    While attachment has been a fruitful and critical concept in understanding enduring individual templates for interpersonal relationships, it does not have a well-understood relationship to personality disorders, where impairment of interpersonal functioning is paramount. Despite the recognition that attachment disturbances do not simply reflect nonoptimal caretaking environments, the relationship of underlying temperamental factors to these environmental insults has not been fully explored. In this paper we provide an alternate model for the role of neurobiological temperamental factors, including brain circuitry and neuropeptide modulation, in mediating social cognition and the internalization and maintenance of attachment patterns. The implications of these altered attachment patterns on personality disorders and their neurobiological and environmental roots for psychoanalytically based treatment models designed to ameliorate difficulties in interpersonal functioning through the medium of increased access to mature forms of mentalization is discussed.

  17. Day Care and Attachment

    Science.gov (United States)

    Portnoy, Fern C.; Simmons, Carolyn H.

    1978-01-01

    The attachment behavior of 35 white, middle-class 3 1/2- to 4-year-olds who had experienced different rearing histories was observed through a series of standardized episodes involving separations and reunions with the mother and a stranger. (Author/JMB)

  18. Attachment and Personality Disorders

    Science.gov (United States)

    Sinha, Preeti; Sharan, Pratap

    2007-01-01

    Personality disorders (PDs) arise from core psychopathology of interpersonal relationships and understanding of self and others. The distorted representations of self and others, as well as unhealthy relationships that characterize persons with various PDs, indicate the possibility that persons with PDs have insecure attachment. Insecure…

  19. God attachment, mother attachment, and father attachment in early and middle adolescence.

    Science.gov (United States)

    Sim, Tick Ngee; Yow, Amanda Shixian

    2011-06-01

    The present study examined the interplay of attachment to God, attachment to mother, and attachment to father with respect to adjustment (hope, self-esteem, depression) for 130 early and 106 middle adolescents in Singapore. Results showed that the parental attachments were generally linked (in expected directions) to adjustment. God attachment, however, had unique results. At the bivariate level, God attachment was only linked to early adolescents' self-esteem. When considered together with parental attachments (including interactions), God attachment did not emerge as the key moderator in attachment interactions and yielded some unexpected results (e.g., being positively linked to depression). These results are discussed viz-a-viz the secure base and safe haven functions that God and parental attachments may play during adolescence.

  20. Highly ordered structures of peptides by using molecular scaffolds.

    Science.gov (United States)

    Moriuchi, Toshiyuki; Hirao, Toshikazu

    2004-06-20

    Protein secondary structures such as alpha-helices, beta-sheets, and beta-turns are important in inducing the three-dimensional structure and biological activity of proteins. Designing secondary structure mimics composed of short peptides has attracted much attention not only to gain fundamental insight into the factors affecting protein folding but also to develop pharmacologically useful compounds, artificial receptors, asymmetric catalysts, and new materials. In this tutorial review, we focus on molecular scaffolds employed to induce beta-sheet-like structure in attached peptide chains, thereby creating highly ordered molecular structures, and discuss the versatility of these molecular scaffolds to regulate the attached peptide strands in the appropriate dimensions.

  1. Studies towards the understanding of the effects of ionizing radiations at the molecular scale (20-150 keV H{sup +}/H + He Collisions; dissociative electron attachment to water)

    Energy Technology Data Exchange (ETDEWEB)

    Coupier, B

    2005-11-15

    This work comes within the scope of recent studies towards a better understanding of the effect of ionizing radiation at the molecular scale on biological systems. It is composed of two parts. The first one presents a new set of coincidence measurements of cross sections for the impact of protons or hydrogen atoms on helium in the energy range 20-150 keV of interest for the radiation biology. It is an archetypical system of interest for the theoreticians and there exists only a few studies on the impact of hydrogen atoms on helium. This study with helium was also motivated for the sake of performing a general test of functioning of the apparatus before investigating more complicated systems. Similar studies were then performed by replacing helium with water and biological molecules of relevance (Uracil, Thymine...) as target. This constitutes a study of direct effects of fast ionizing radiations on molecules of biological interest. The second part of the thesis deals with another type of ionizing radiations which can be seen as indirect effects of the first fast ionizing radiations studied in the first part. Low energy electrons emission in the energy range 1 to 16 eV follows the bombardment of the matter by swift protons/hydrogen atoms; these electrons have in turn an ionizing influence on the environment. A review of the dissociative electron attachment to water was undertaken motivated by the existing discrepancies between old studies on the same subject. A special attention was given to the problem of high energy kinetic ion discrimination in the trochoidal monochromator used for this work. (author)

  2. Novel ligands of Choline Acetyltransferase designed by in silico molecular docking, hologram QSAR and lead optimization.

    Science.gov (United States)

    Kumar, Rajnish; Långström, Bengt; Darreh-Shori, Taher

    2016-01-01

    Recent reports have brought back the acetylcholine synthesizing enzyme, choline acetyltransferase in the mainstream research in dementia and the cholinergic anti-inflammatory pathway. Here we report, a specific strategy for the design of novel ChAT ligands based on molecular docking, Hologram Quantitative Structure Activity Relationship (HQSAR) and lead optimization. Molecular docking was performed on a series of ChAT inhibitors to decipher the molecular fingerprint of their interaction with the active site of ChAT. Then robust statistical fragment HQSAR models were developed. A library of novel ligands was generated based on the pharmacophoric and shape similarity scoring function, and evaluated in silico for their molecular interactions with ChAT. Ten of the top scoring invented compounds are reported here. We confirmed the activity of α-NETA, the only commercially available ChAT inhibitor, and one of the seed compounds in our model, using a new simple colorimetric ChAT assay (IC50 ~ 88 nM). In contrast, α-NETA exhibited an IC50 of ~30 μM for the ACh-degrading cholinesterases. In conclusion, the overall results may provide useful insight for discovering novel ChAT ligands and potential positron emission tomography tracers as in vivo functional biomarkers of the health of central cholinergic system in neurodegenerative disorders, such as Alzheimer's disease.

  3. In-silico design of computational nucleic acids for molecular information processing.

    Science.gov (United States)

    Ramlan, Effirul Ikhwan; Zauner, Klaus-Peter

    2013-05-07

    Within recent years nucleic acids have become a focus of interest for prototype implementations of molecular computing concepts. During the same period the importance of ribonucleic acids as components of the regulatory networks within living cells has increasingly been revealed. Molecular computers are attractive due to their ability to function within a biological system; an application area extraneous to the present information technology paradigm. The existence of natural information processing architectures (predominately exemplified by protein) demonstrates that computing based on physical substrates that are radically different from silicon is feasible. Two key principles underlie molecular level information processing in organisms: conformational dynamics of macromolecules and self-assembly of macromolecules. Nucleic acids support both principles, and moreover computational design of these molecules is practicable. This study demonstrates the simplicity with which one can construct a set of nucleic acid computing units using a new computational protocol. With the new protocol, diverse classes of nucleic acids imitating the complete set of boolean logical operators were constructed. These nucleic acid classes display favourable thermodynamic properties and are significantly similar to the approximation of successful candidates implemented in the laboratory. This new protocol would enable the construction of a network of interconnecting nucleic acids (as a circuit) for molecular information processing.

  4. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-05-05

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  5. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M.

    2016-05-01

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  6. Bioprocess-centered molecular design (BMD) for the efficient production of an interfacially active peptide.

    Science.gov (United States)

    Morreale, Giacomo; Lee, Eun Gyo; Jones, Daniel B; Middelberg, Anton P J

    2004-09-30

    The efficient expression and purification of an interfacially active peptide (mLac21) was achieved by using bioprocess-centered molecular design (BMD), wherein key bioprocess considerations are addressed during the initial molecular biology work. The 21 amino acid mLac21 peptide sequence is derived from the lac repressor protein and is shown to have high affinity for the oil-water interface, causing a substantial reduction in interfacial tension following adsorption. The DNA coding for the peptide sequence was cloned into a modified pET-31(b) vector to permit the expression of mLac21 as a fusion to ketosteroid isomerase (KSI). Rational iterative molecular design, taking into account the need for a scaleable bioprocess flowsheet, led to a simple and efficient bioprocess yielding mLac21 at 86% purity following ion exchange chromatography (and >98% following chromatographic polishing). This case study demonstrates that it is possible to produce acceptably pure peptide for potential commodity applications using common scaleable bioprocess unit operations. Moreover, it is shown that BMD is a powerful strategy that can be deployed to reduce bioseparation complexity.

  7. Tuning Cellular Uptake of Molecular Probes by Rational Design of Their Assembly into Supramolecular Nanoprobes.

    Science.gov (United States)

    Lock, Lye Lin; Reyes, Claudia D; Zhang, Pengcheng; Cui, Honggang

    2016-03-16

    Intracellular sensing of pathologically relevant biomolecules could provide essential information for accurate evaluation of disease staging and progression, yet the poor cellular uptake of water-soluble molecular probes limits their use as protease sensors. In other cases such as extracellular sensing, cellular uptake should be effectively inhibited. Self-assembly of molecular probes into supramolecular nanoprobes presents a potential strategy to alter their interaction mechanisms with cells to promote or reduce their cellular uptake. Here, we report on the design, synthesis, and assembly of peptide-based molecular beacons into supramolecular protease sensors of either spherical or filamentous shapes. We found that positively charged spherical nanobeacons demonstrate much higher cellular uptake efficiency than its monomeric form, thus making them most suitable for intracellular sensing of the lysosomal protease cathepsin B. Our results also suggest that assembly into filamentous nanobeacons significantly reduces their internalization by cancer cells, an important property that can be utilized for probing extracellular protease activities. These studies provide important guiding principles for rational design of supramolecular nanoprobes with tunable cellular uptake characteristics.

  8. Remedial action plan and site design for stabilization of the inactive uranium processing site at Naturita, Colorado. Remedial Action Selection Report, Appendix B of Attachment 2: Geology report, Final

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    The uranium processing site near Naturita, Colorado, is one of 24 inactive uranium mill sites designated to be cleaned up by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA), 42 USC {section} 7901 et seq. Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE`s remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). Included in the RAP is this Remedial Action Selection Report (RAS), which describes the proposed remedial action for the Naturita site. An extensive amount of data and supporting information has been generated and evaluated for this remedial action. These data and supporting information are not incorporated into this single document but are included or referenced in the supporting documents. The RAP consists of this RAS and four supporting documents or attachments. This Attachment 2, Geology Report describes the details of geologic, geomorphic, and seismic conditions at the Dry Flats disposal site.

  9. De novo design of caseinolytic protein proteases inhibitors based on pharmacophore and 2D molecular fingerprints.

    Science.gov (United States)

    Wu, Guanzhong; Zhang, Zhen; Chen, Hong; Lin, Kejiang

    2015-06-01

    Caseinolytic protein proteases (ClpP) are large oligomeric protein complexes that contribute to cell homeostasis as well as virulence regulation in bacteria. Inhibitors of ClpP can significantly attenuate the capability to produce virulence factors of the bacteria. In this work, we developed a workflow to expand the chemical space of potential ClpP inhibitors based on a set of β-lactones. In our workflow, an artificial pharmacophore model was generated based on HipHop and HYPOGEN method. A de novo compound library based on molecular fingerprints was constructed and virtually screened by the pharmacophore model. The results were further investigated by molecular docking study. The workflow successfully achieved potential ClpP inhibitors. It could be applied to design more novel potential ClpP inhibitors and provide theoretical basis for the further optimization of the hit compounds.

  10. Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.

    Science.gov (United States)

    Ye, Lianbao; Ou, Xiaomin; Tian, Yuanxin; Yu, Bangwei; Luo, Yan; Feng, Binghong; Lin, Hansen; Zhang, Jiajie; Wu, Shuguang

    2013-07-01

    Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 μM in TR-FRET-based assay and IC50 value of 5.45 μM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.

  11. Picturing Urban Green Attachments

    DEFF Research Database (Denmark)

    Blok, Anders; Meilvang, Marie Leth

    2015-01-01

    in the plural’ in the city. In particular, we stress the role assumed in such engagements by various image-making practices, as means for activists to express, share and render publicly visible a range of embodied urban attachments. Pragmatic sociology, we conclude, may contribute to a novel understanding......In this article, we explore the cultural-political tensions and ambiguities of urban ecology, by way of following how activists move and translate between ‘familiar’ and ‘public’ engagements in the green city. Empirically, we locate our exploration in and around Nordhavnen (The North Harbor...... of urban politics as inclusive learning processes, more hospitable to a wider diversity of familiar attachments to cities and their ecologies....

  12. Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory.

    Science.gov (United States)

    Mrugalla, Florian; Kast, Stefan M

    2016-09-01

    Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

  13. Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory

    Science.gov (United States)

    Mrugalla, Florian; Kast, Stefan M.

    2016-09-01

    Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

  14. The Folding of de Novo Designed Protein DS119 via Molecular Dynamics Simulations.

    Science.gov (United States)

    Wang, Moye; Hu, Jie; Zhang, Zhuqing

    2016-04-26

    As they are not subjected to natural selection process, de novo designed proteins usually fold in a manner different from natural proteins. Recently, a de novo designed mini-protein DS119, with a βαβ motif and 36 amino acids, has folded unusually slowly in experiments, and transient dimers have been detected in the folding process. Here, by means of all-atom replica exchange molecular dynamics (REMD) simulations, several comparably stable intermediate states were observed on the folding free-energy landscape of DS119. Conventional molecular dynamics (CMD) simulations showed that when two unfolded DS119 proteins bound together, most binding sites of dimeric aggregates were located at the N-terminal segment, especially residues 5-10, which were supposed to form β-sheet with its own C-terminal segment. Furthermore, a large percentage of individual proteins in the dimeric aggregates adopted conformations similar to those in the intermediate states observed in REMD simulations. These results indicate that, during the folding process, DS119 can easily become trapped in intermediate states. Then, with diffusion, a transient dimer would be formed and stabilized with the binding interface located at N-terminals. This means that it could not quickly fold to the native structure. The complicated folding manner of DS119 implies the important influence of natural selection on protein-folding kinetics, and more improvement should be achieved in rational protein design.

  15. Molecular design and evaluation of biodegradable polymers using a statistical approach.

    Science.gov (United States)

    Lewitus, Dan Y; Rios, Fabian; Rojas, Ramiro; Kohn, Joachim

    2013-11-01

    The challenging paradigm of bioresorbable polymers, whether in drug delivery or tissue engineering, states that a fine-tuning of the interplay between polymer properties (e.g., thermal, degradation), and the degree of cell/tissue replacement and remodeling is required. In this paper we describe how changes in the molecular architecture of a series of terpolymers allow for the design of polymers with varying glass transition temperatures and degradation rates. The effect of each component in the terpolymers is quantified via design of experiment (DoE) analysis. A linear relationship between terpolymer components and resulting Tg (ranging from 34 to 86 °C) was demonstrated. These findings were further supported with mass-per-flexible-bond analysis. The effect of terpolymer composition on the in vitro degradation of these polymers revealed molecular weight loss ranging from 20 to 60 % within the first 24 h. DoE modeling further illustrated the linear (but reciprocal) relationship between structure elements and degradation for these polymers. Thus, we describe a simple technique to provide insight into the structure property relationship of degradable polymers, specifically applied using a new family of tyrosine-derived polycarbonates, allowing for optimal design of materials for specific applications.

  16. Molecular Design and Evaluation of Biodegradable Polymers Using a Statistical Approach

    Science.gov (United States)

    Lewitus, Dan; Rios, Fabian; Rojas, Ramiro; Kohn, Joachim

    2013-01-01

    The challenging paradigm of bioresorbable polymers, whether in drug delivery or tissue engineering, states that a fine-tuning of the interplay between polymer properties (e.g., thermal, degradation), and the degree of cell/tissue replacement and remodeling is required. In this paper we describe how changes in the molecular architecture of a series of terpolymers allow for the design of polymers with varying glass transition temperatures and degradation rates. The effect of each component in the terpolymers is quantified via design of experiment (DoE) analysis. A linear relationship between terpolymer components and resulting Tg (ranging from 34 to 86 °C) was demonstrated. These findings were further supported with mass-per-flexible-bond (MPFB) analysis. The effect of terpolymer composition on the in vitro degradation of these polymers revealed molecular weight loss ranging from 20 to 60% within the first 24 hours. DoE modeling further illustrated the linear (but reciprocal) relationship between structure elements and degradation for these polymers. Thus, we describe a simple technique to provide insight into the structure property relationship of degradable polymers, specifically applied using a new family of tyrosine-derived polycarbonates, allowing for optimal design of materials for specific applications. PMID:23888354

  17. PathogenMIPer: a tool for the design of molecular inversion probes to detect multiple pathogens

    Directory of Open Access Journals (Sweden)

    Akhras Michael

    2006-11-01

    Full Text Available Abstract Background Here we describe PathogenMIPer, a software program for designing molecular inversion probe (MIP oligonucleotides for use in pathogen identification and detection. The software designs unique and specific oligonucleotide probes targeting microbial or other genomes. The tool tailors all probe sequence components (including target-specific sequences, barcode sequences, universal primers and restriction sites and combines these components into ready-to-order probes for use in a MIP assay. The system can harness the genetic variability available in an entire genome in designing specific probes for the detection of multiple co-infections in a single tube using a MIP assay. Results PathogenMIPer can accept sequence data in FASTA file format, and other parameter inputs from the user through a graphical user interface. It can design MIPs not only for pathogens, but for any genome for use in parallel genomic analyses. The software was validated experimentally by applying it to the detection of human papilloma virus (HPV as a model system, which is associated with various human malignancies including cervical and skin cancers. Initial tests of laboratory samples using the MIPs developed by the PathogenMIPer to recognize 24 different types of HPVs gave very promising results, detecting even a small viral load of single as well as multiple infections (Akhras et al, personal communication. Conclusion PathogenMIPer is a software for designing molecular inversion probes for detection of multiple target DNAs in a sample using MIP assays. It enables broader use of MIP technology in the detection through genotyping of pathogens that are complex, difficult-to-amplify, or present in multiple subtypes in a sample.

  18. Design of a Comprehensive Biochemistry and Molecular Biology Experiment: Phase Variation Caused by Recombinational Regulation of Bacterial Gene Expression

    Science.gov (United States)

    Sheng, Xiumei; Xu, Shungao; Lu, Renyun; Isaac, Dadzie; Zhang, Xueyi; Zhang, Haifang; Wang, Huifang; Qiao, Zheng; Huang, Xinxiang

    2014-01-01

    Scientific experiments are indispensable parts of Biochemistry and Molecular Biology. In this study, a comprehensive Biochemistry and Molecular Biology experiment about "Salmonella enterica" serovar Typhi Flagellar phase variation has been designed. It consisted of three parts, namely, inducement of bacterial Flagellar phase variation,…

  19. Molecular Design and Functional Control of Novel Self-Oscillating Polymers

    Directory of Open Access Journals (Sweden)

    Ryo Yoshida

    2010-02-01

    Full Text Available If we could realize an autonomous polymer system driven under biological conditions by a tailor-made molecular design, human beings could create unprecedented biomimetic functions and materials such as heartbeats, autonomous peristaltic pumps, etc. In order to achieve this objective, we have investigated the molecular design of such a polymer system. As a result, we were the first to demonstrate a self-oscillating polymer system driven in a solution where only malonic acid existed, which could convert the chemical energy of the Belousov-Zhabotinsky (BZ reaction into a change in the conformation of the polymer chain. To cause the self-oscillation in solution, we have attempted to construct a built-in system where the required BZ system substrates other than the organic acid are incorporated into the polymer itself. That is, the novel polymer chain incorporated the metal catalyst of the BZ reaction, a pH-control site and an oxidant supply site at the same time. As a result of introducing the pH control and oxidant supply sites into the conventional-type self-oscillating polymer chain, the novel polymer chain caused aggregation-disaggregation self-oscillations in the solution. We clarified that the period of the self-oscillation of the novel self-oscillating polymer chain was proportional to the concentration of the malonic acid. Therefore, the concentration of the malonic acid can be determined by measuring the period of the novel self-oscillating polymer solution. In this review, we introduce the detailed molecular design of the novel self-oscillating polymer chain and its self-oscillating behavior. Moreover, we report an autonomous self-oscillating polymer gel actuator that causes a bending-stretching motion under the constant conditions.

  20. Prediction of mutant activity and its application in molecular design of tumor necrosis factor-a

    Institute of Scientific and Technical Information of China (English)

    唐卫东; 奚涛; 王波; 郭冬林; 徐贤秀; 朱德煦

    1997-01-01

    Two models for prediction of the activity and stability of site-directed mutagenesis on tumor necrosis factor-α are established. The models are based on straightforward structural considerations, which do not require the elaboration of site-directed mutagenesis on the protein core and the hydrophobic surface area by analyzing the properties of the mutated amino acid residues. The reliabilities of the models have been tested by analyzing the mutants of tumor necrosis factor-α (TNF-α) whose two leucine residues (L29, L157) were mutated. Based on these models, a TNF-α mutant with high activity was created by molecular design.

  1. Molecular design chemical structure generation from the properties of pure organic compounds

    CERN Document Server

    Horvath, AL

    1992-01-01

    This book is a systematic presentation of the methods that have been developed for the interpretation of molecular modeling to the design of new chemicals. The main feature of the compilation is the co-ordination of the various scientific disciplines required for the generation of new compounds. The five chapters deal with such areas as structure and properties of organic compounds, relationships between structure and properties, and models for structure generation. The subject is covered in sufficient depth to provide readers with the necessary background to understand the modeling

  2. No Strings Attached: Open Source Solutions

    Science.gov (United States)

    Fredricks, Kathy

    2009-01-01

    Imagine downloading a new software application and not having to worry about licensing, finding dollars in the budget, or incurring additional maintenance costs. Imagine finding a Web design tool in the public domain--free for use. Imagine major universities that provide online courses with no strings attached. Imagine online textbooks without a…

  3. Molecular Design of Semiconducting Polymers for High-Performance Organic Electrochemical Transistors.

    Science.gov (United States)

    Nielsen, Christian B; Giovannitti, Alexander; Sbircea, Dan-Tiberiu; Bandiello, Enrico; Niazi, Muhammad R; Hanifi, David A; Sessolo, Michele; Amassian, Aram; Malliaras, George G; Rivnay, Jonathan; McCulloch, Iain

    2016-08-17

    The organic electrochemical transistor (OECT), capable of transducing small ionic fluxes into electronic signals in an aqueous environment, is an ideal device to utilize in bioelectronic applications. Currently, most OECTs are fabricated with commercially available conducting poly(3,4-ethylenedioxythiophene) (PEDOT)-based suspensions and are therefore operated in depletion mode. Here, we present a series of semiconducting polymers designed to elucidate important structure-property guidelines required for accumulation mode OECT operation. We discuss key aspects relating to OECT performance such as ion and hole transport, electrochromic properties, operational voltage, and stability. The demonstration of our molecular design strategy is the fabrication of accumulation mode OECTs that clearly outperform state-of-the-art PEDOT-based devices, and show stability under aqueous operation without the need for formulation additives and cross-linkers.

  4. Molecular design, synthesis and cell based HCV replicon assay of novel benzoxazole derivatives.

    Science.gov (United States)

    Ismail, M A H; Adel, M; Ismail, N S M; Abouzid, K A M

    2013-03-01

    Hepatitis C virus inhibitors based on benzoxazole scaffold were designed based on molecular modeling simulation study including docking into the NS5B polymerase active site. Several compounds showed significant high simulation docking scores relative to the assigned benzimidazole lead compound. The designed compounds were synthesized, structurally elucidated and their antiviral activity was evaluated through cell-based replicon in cultured Huh 5-2 cells. A number of the synthesized compounds showed significant inhibitory activity ranging from (52.2% inhibition up to 98% at<50 µg/mL). N-Benzyl-2-phenylbenzo[1,3]oxazole-5-carboxamide (8b) and N-Phenethyl-2-phenylbenzo[1,3] oxazole-5-carboxamide (8c) demonstrated genuine HCV inhibitory activity with EC50 values of 41.6 and 24.5 µg/mL respectively.

  5. Molecular Design of Semiconducting Polymers for High-Performance Organic Electrochemical Transistors

    KAUST Repository

    Nielsen, Christian B.

    2016-07-22

    The organic electrochemical transistor (OECT), capable of transducing small ionic fluxes into electronic signals in an aqueous envi-ronment, is an ideal device to utilize in bioelectronic applications. Currently, most OECTs are fabricated with commercially availa-ble conducting poly(3,4-ethylenedioxythiophene) (PEDOT)-based suspensions and are therefore operated in depletion mode. Here, we present a series of semiconducting polymers designed to elucidate important structure-property guidelines required for accumulation mode OECT operation. We discuss key aspects relating to OECT performance such as ion and hole transport, elec-trochromic properties, operational voltage and stability. The demonstration of our molecular design strategy is the fabrication of accumulation mode OECTs that clearly outperform state-of-the-art PEDOT based devices, and show stability under aqueous oper-ation without the need for formulation additives and cross-linkers.

  6. Design of Skin Penetration Enhancers Using Replacement Methods for the Selection of the Molecular Descriptors

    Directory of Open Access Journals (Sweden)

    Beshoy Abdelmalek

    2012-07-01

    Full Text Available Transdermal delivery of certain drugs is challenging because of skin barrier resistance. This study focuses on the implementation of feature-selection algorithms to design chemical penetration enhancers. A database, consisting of 145 polar and nonpolar chemicals, was chosen for the investigation. Replacement, enhanced replacement and stepwise algorithms were applied to identify relevant structural properties of these compounds. The descriptors were calculated using Molecular Modeling Pro™ Plus. Based on the coefficient of determination, the replacement methods outperformed the stepwise approach in selecting the features that best correlated with the flux enhancement ratio. An artificial neural network model was built to map a subset of descriptors from sixty-one nonpolar enhancers onto the output vector. The R2 value improved from 0.68, for a linear model, to 0.74, which shows that the improved framework might be effective in the design of compounds with user-defined properties.

  7. Halogen-directed drug design for Alzheimer's disease: a combined density functional and molecular docking study.

    Science.gov (United States)

    Rahman, Adhip; Ali, Mohammad Tuhin; Shawan, Mohammad Mahfuz Ali Khan; Sarwar, Mohammed Golam; Khan, Mohammad A K; Halim, Mohammad A

    2016-01-01

    A series of halogen-directed donepezil drugs has been designed to inhibit acetyl cholinesterase (AChE). Density Functional theory (DFT) has been employed to optimize the chair as well as boat conformers of the parent drug and modified ligands at B3LYP/MidiX and B3LYP/6-311G + (d,p) level of theories. Charge distribution, dipole moment, enthalpy, free energy and molecular orbitals of these ligands are also investigated to understand how the halogen-directed modifications impact the ligand structure and govern the non-bonding interactions with the receptors. Molecular docking calculation has been performed to understand the similarities and differences between the binding modes of unmodified and halogenated chair-formed ligands. Molecular docking indicated donepezil and modified ligands had non-covalent interactions with hydrophobic gorges and anionic subsites of AChE. The -CF3-directed ligand possessed the most negative binding affinity. Non-covalent interactions within the ligand-receptor systems were found to be mostly hydrophobic and π- stacking type. F, Cl and -CF3 containing ligands emerge as effective and selective AChE inhibitors, which can strongly interact with the two active sites of AChE. In addition, we have also investigated selected pharmacokinetic parameters of the parent and modified ligands.

  8. New mimetic peptides inhibitors of Αβ aggregation. Molecular guidance for rational drug design.

    Science.gov (United States)

    Barrera Guisasola, Exequiel E; Andujar, Sebastián A; Hubin, Ellen; Broersen, Kerensa; Kraan, Ivonne M; Méndez, Luciana; Delpiccolo, Carina M L; Masman, Marcelo F; Rodríguez, Ana M; Enriz, Ricardo D

    2015-05-01

    A new series of mimetic peptides possessing a significant Aβ aggregation modulating effect was reported here. These compounds were obtained based on a molecular modelling study which allowed us to perform a structural-based virtual selection. Monitoring Aβ aggregation by thioflavin T fluorescence and transmission electron microscopy revealed that fibril formation was significantly decreased upon prolonged incubation in presence of the active compounds. Dot blot analysis suggested a decrease of soluble oligomers strongly associated with cognitive decline in Alzheimer's disease. For the molecular dynamics simulations, we used an Aβ42 pentameric model where the compounds were docked using a blind docking technique. To analyze the dynamic behaviour of the complexes, extensive molecular dynamics simulations were carried out in explicit water. We also measured parameters or descriptors that allowed us to quantify the effect of these compounds as potential inhibitors of Aβ aggregation. Thus, significant alterations in the structure of our Aβ42 protofibril model were identified. Among others we observed the destruction of the regular helical twist, the loss of a stabilizing salt bridge and the loss of a stabilizing hydrophobic interaction in the β1 region. Our results may be helpful in the structural identification and understanding of the minimum structural requirements for these molecules and might provide a guide in the design of new aggregation modulating ligands.

  9. Molecular design and control of fullerene-based bi-thermoelectric materials.

    Science.gov (United States)

    Rincón-García, Laura; Ismael, Ali K; Evangeli, Charalambos; Grace, Iain; Rubio-Bollinger, Gabino; Porfyrakis, Kyriakos; Agraït, Nicolás; Lambert, Colin J

    2016-03-01

    Molecular junctions are a versatile test bed for investigating nanoscale thermoelectricity and contribute to the design of new cost-effective environmentally friendly organic thermoelectric materials. It was suggested that transport resonances associated with discrete molecular levels could play a key role in thermoelectric performance, but no direct experimental evidence has been reported. Here we study single-molecule junctions of the endohedral fullerene Sc3N@C80 connected to gold electrodes using a scanning tunnelling microscope. We find that the magnitude and sign of the thermopower depend strongly on the orientation of the molecule and on applied pressure. Our calculations show that Sc3N inside the fullerene cage creates a sharp resonance near the Fermi level, whose energetic location, and hence the thermopower, can be tuned by applying pressure. These results reveal that Sc3N@C80 is a bi-thermoelectric material, exhibiting both positive and negative thermopower, and provide an unambiguous demonstration of the importance of transport resonances in molecular junctions.

  10. The Design and Transformation of Biofundamentals: A Nonsurvey Introductory Evolutionary and Molecular Biology Course.

    Science.gov (United States)

    Klymkowsky, Michael W; Rentsch, Jeremy D; Begovic, Emina; Cooper, Melanie M

    2016-01-01

    Many introductory biology courses amount to superficial surveys of disconnected topics. Often, foundational observations and the concepts derived from them and students' ability to use these ideas appropriately are overlooked, leading to unrealistic expectations and unrecognized learning obstacles. The result can be a focus on memorization at the expense of the development of a meaningful framework within which to consider biological phenomena. About a decade ago, we began a reconsideration of what an introductory course should present to students and the skills they need to master. The original Web-based course's design presaged many of the recommendations of the Vision and Change report; in particular, a focus on social evolutionary mechanisms, stochastic (evolutionary and molecular) processes, and core ideas (cellular continuity, evolutionary homology, molecular interactions, coupled chemical reactions, and molecular machines). Inspired by insights from the Chemistry, Life, the Universe & Everything general chemistry project, we transformed the original Web version into a (freely available) book with a more unified narrative flow and a set of formative assessments delivered through the beSocratic system. We outline how student responses to course materials are guiding future course modifications, in particular a more concerted effort at helping students to construct logical, empirically based arguments, explanations, and models.

  11. Attachment: Theoretical Development and Critique

    Science.gov (United States)

    Slater, Ruth

    2007-01-01

    Zeanah argues that ethological attachment theory, as outlined by John Bowlby, has provided one of the most important frameworks for understanding crucial risk and protective factors in social and emotional development. However, although attachment theory and the notion of attachment disorders have influenced such initiatives, many psychologists,…

  12. Attachment Theory: Retrospect and Prospect.

    Science.gov (United States)

    Bretherton, Inge

    1985-01-01

    Provides overview of attachment theory as parented by John Bowlby in "Attachment and Loss". Uses two major concepts from this work to interpret refinements and elaborations of attachment theory attibuted to Mary Ainsworth. Considers how recent insights into development of socioemotional understanding and development of event…

  13. Adopting Children with Attachment Problems.

    Science.gov (United States)

    Hughes, Daniel A.

    1999-01-01

    Notes that attachment behavior in infants is a facet of normal child development, and that children with attachment problems require special attention during and after the adoption process. Presents actions needed to increase the probability that such children can be successfully adopted, detailed attachment patterns, and parenting strategies and…

  14. Attachment Theory: Retrospect and Prospect.

    Science.gov (United States)

    Bretherton, Inge

    1985-01-01

    Provides overview of attachment theory as parented by John Bowlby in "Attachment and Loss". Uses two major concepts from this work to interpret refinements and elaborations of attachment theory attibuted to Mary Ainsworth. Considers how recent insights into development of socioemotional understanding and development of event representation can be…

  15. Design and synthesis of molecular donors for solution-processed high-efficiency organic solar cells.

    Science.gov (United States)

    Coughlin, Jessica E; Henson, Zachary B; Welch, Gregory C; Bazan, Guillermo C

    2014-01-21

    Organic semiconductors incorporated into solar cells using a bulk heterojunction (BHJ) construction show promise as a cleaner answer to increasing energy needs throughout the world. Organic solar cells based on the BHJ architecture have steadily increased in their device performance over the past two decades, with power conversion efficiencies reaching 10%. Much of this success has come with conjugated polymer/fullerene combinations, where optimized polymer design strategies, synthetic protocols, device fabrication procedures, and characterization methods have provided significant advancements in the technology. More recently, chemists have been paying particular attention to well-defined molecular donor systems due to their ease of functionalization, amenability to standard organic purification and characterization methods, and reduced batch-to-batch variability compared to polymer counterparts. There are several critical properties for efficient small molecule donors. First, broad optical absorption needs to extend towards the near-IR region to achieve spectral overlap with the solar spectrum. Second, the low lying highest occupied molecular orbital (HOMO) energy levels need to be between -5.2 and -5.5 eV to ensure acceptable device open circuit voltages. Third, the structures need to be relatively planar to ensure close intermolecular contacts and high charge carrier mobilities. And last, the small molecule donors need to be sufficiently soluble in organic solvents (≥10 mg/mL) to facilitate solution deposition of thin films of appropriate uniformity and thickness. Ideally, these molecules should be constructed from cost-effective, sustainable building blocks using established, high yielding reactions in as few steps as possible. The structures should also be easy to functionalize to maximize tunability for desired properties. In this Account, we present a chronological description of our thought process and design strategies used in the development of highly

  16. Current Tools and Methods in Molecular Dynamics (MD) Simulations for Drug Design.

    Science.gov (United States)

    Hernández-Rodríguez, Maricarmen; Rosales-Hernández, Martha C; Mendieta-Wejebe, Jessica E; Martínez-Archundia, Marlet; Basurto, José Correa

    2016-01-01

    Molecular Dynamics (MD) simulations is a computational method that employs Newton's laws to evaluate the motions of water, ions, small molecules, and macromolecules or more complex systems, for example, whole viruses, to reproduce the behavior of the biological environment, including water molecules and lipid membranes. Specifically, structural motions, such as those that are dependent of the temperature and solute/ solvent are very important to study the recognition pattern of ligandprotein or protein-protein complexes, in that sense, MD simulations are very useful because these motions can be modeled using this methodology. Furthermore, MD simulations for drug design provide insights into the structural cavities required to design novel structures with higher affinity to the target. Also, the employment of MD simulations to drug design can help to refine the three-dimensional (3D) structure of targets in order to obtain a better sampling of the binding poses and more reliable affinity values with better structural advantages, because they incorporate some biological conditions that include structural motions compared to traditional docking procedures. This work analyzes the concepts and applicability of MD simulations for drug design because molecular structural motions are considered, and these help to identify hot spots, decipher structural details in the reported protein sites, as well as to eliminate sites that could be structural artifacts which could be originated from the structural characterization conditions from MD. Moreover, better free energy values for protein ligand recognition can also be obtained, and these can be validated under experimental procedures due to the robustness of the MD simulation methods.

  17. A multiscale simulation technique for molecular electronics: design of a directed self-assembled molecular n-bit shift register memory device.

    Science.gov (United States)

    Lambropoulos, Nicholas A; Reimers, Jeffrey R; Crossley, Maxwell J; Hush, Noel S; Silverbrook, Kia

    2013-12-20

    A general method useful in molecular electronics design is developed that integrates modelling on the nano-scale (using quantum-chemical software) and on the micro-scale (using finite-element methods). It is applied to the design of an n-bit shift register memory that could conceivably be built using accessible technologies. To achieve this, the entire complex structure of the device would be built to atomic precision using feedback-controlled lithography to provide atomic-level control of silicon devices, controlled wet-chemical synthesis of molecular insulating pillars above the silicon, and controlled wet-chemical self-assembly of modular molecular devices to these pillars that connect to external metal electrodes (leads). The shift register consists of n connected cells that read data from an input electrode, pass it sequentially between the cells under the control of two external clock electrodes, and deliver it finally to an output device. The proposed cells are trimeric oligoporphyrin units whose internal states are manipulated to provide functionality, covalently connected to other cells via dipeptide linkages. Signals from the clock electrodes are conveyed by oligoporphyrin molecular wires, and μ-oxo porphyrin insulating columns are used as the supporting pillars. The developed multiscale modelling technique is applied to determine the characteristics of this molecular device, with in particular utilization of the inverted region for molecular electron-transfer processes shown to facilitate latching and control using exceptionally low energy costs per logic operation compared to standard CMOS shift register technology.

  18. Integration of Molecular Dynamics Based Predictions into the Optimization of De Novo Protein Designs: Limitations and Benefits.

    Science.gov (United States)

    Carvalho, Henrique F; Barbosa, Arménio J M; Roque, Ana C A; Iranzo, Olga; Branco, Ricardo J F

    2017-01-01

    Recent advances in de novo protein design have gained considerable insight from the intrinsic dynamics of proteins, based on the integration of molecular dynamics simulations protocols on the state-of-the-art de novo protein design protocols used nowadays. With this protocol we illustrate how to set up and run a molecular dynamics simulation followed by a functional protein dynamics analysis. New users will be introduced to some useful open-source computational tools, including the GROMACS molecular dynamics simulation software package and ProDy for protein structural dynamics analysis.

  19. Computer Aided Drug Design for Multi-Target Drug Design: SAR /QSAR, Molecular Docking and Pharmacophore Methods.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B; Ghasemi, Fatemeh

    2017-01-01

    Multi-target drugs against particular multiple targets get better protection, resistance profiles and curative influence by cooperative rules of a key beneficial target with resistance behavior and compensatory elements. Computational techniques can assist us in the efforts to design novel drugs (ligands) with a preferred bioactivity outline and alternative bioactive molecules at an early stage. A number of in silico methods have been explored extensively in order to facilitate the investigation of individual target agents and to propose a selective drug. A different, progressively more significant field which is used to predict the bioactivity of chemical compounds is the data mining method. Some of the previously mentioned methods have been investigated for multi-target drug design (MTDD) to find drug leads interact simultaneously with multiple targets. Several cheminformatics methods and structure-based approaches try to extract information from units working cooperatively in a biomolecular system to fulfill their task. To dominate the difficulties of the experimental specification of ligand-target structures, rational methods, namely molecular docking, SAR and QSAR are vital substitutes to obtain knowledge for each structure in atomic insight. These procedures are logically successful for the prediction of binding affinity and have shown promising potential in facilitating MTDD. Here, we review some of the important features of the multi-target therapeutics discoveries using the computational approach, highlighting the SAR, QSAR, docking and pharmacophore methods to discover interactions between drug-target that could be leveraged for curative benefits. A summary of each, followed by examples of its applications in drug design has been provided. Computational efficiency of each method has been represented according to its main strengths and limitations.

  20. Theoretical descriptions of electron transport through single molecules: Developing design tools for molecular electronic devices

    Science.gov (United States)

    Carroll, Natalie R.

    There are vast numbers of organic compounds that could be considered for use in molecular electronics. Hence there is a need for efficient and economical screening tools. Here we develop theoretical methods to describe electron transport through individual molecules, the ultimate goal of which is to establish design tools for molecular electronic devices. To successfully screen a compound for its use as a device component requires a proper representation of the quantum mechanics of electron transmission. In this work we report the development of tools for the description of electron transmission that are: Charge self-consistent, valid in the presence of a finite applied potential field and (in some cases) explicitly time-dependent. In addition, the tools can be extended to any molecular system, including biosystems, because they are free of restrictive parameterizations. Two approaches are explored: (1) correlation of substituent parameter values (sigma), (commonly found in organic chemistry textbooks) to properties associated with electron transport, (2) explicit tracking of the time evolution of the wave function of a nonstationary electron. In (1) we demonstrate that the a correlate strongly with features of the charge migration process, establishing them as useful indicators of electronic properties. In (2) we employ a time-dependent description of electron transport through molecular junctions. To date, the great majority of theoretical treatments of electron transport in molecular junctions have been of the time-independent variety. Time dependence, however, is critical to such properties as switching speeds in binary computer components and alternating current conductance, so we explored methods based on time-dependent quantum mechanics. A molecular junction is modeled as a single molecule sandwiched between two clusters of close-packed metal atoms or other donor and acceptor groups. The time dependence of electron transport is investigated by initially

  1. Computer-aided Molecular Design of Compounds Targeting Histone Modifying Enzymes.

    Science.gov (United States)

    Andreoli, Federico; Del Rio, Alberto

    2015-01-01

    Growing evidences show that epigenetic mechanisms play crucial roles in the genesis and progression of many physiopathological processes. As a result, research in epigenetic grew at a fast pace in the last decade. In particular, the study of histone post-translational modifications encountered an extraordinary progression and many modifications have been characterized and associated to fundamental biological processes and pathological conditions. Histone modifications are the catalytic result of a large set of enzyme families that operate covalent modifications on specific residues at the histone tails. Taken together, these modifications elicit a complex and concerted processing that greatly contribute to the chromatin remodeling and may drive different pathological conditions, especially cancer. For this reason, several epigenetic targets are currently under validation for drug discovery purposes and different academic and industrial programs have been already launched to produce the first pre-clinical and clinical outcomes. In this scenario, computer-aided molecular design techniques are offering important tools, mainly as a consequence of the increasing structural information available for these targets. In this mini-review we will briefly discuss the most common types of known histone modifications and the corresponding operating enzymes by emphasizing the computer-aided molecular design approaches that can be of use to speed-up the efforts to generate new pharmaceutically relevant compounds.

  2. Molecular Design of Doped Polymers for Thermoelectric Systems-Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Chabinyc, Michael L. [University of California, Santa Barbara; Hawker, Craig J. [University of California, Santa Barbara

    2013-10-09

    The self-assembly of organic semiconducting molecules and polymers is critical for their electrical properties. This project addressed the design of organic semiconductors with novel synthetic building blocks for proton-dopable conducting materials and the molecular order and microstructure of high performance semiconducting polymers blended with charge transfer dopants. Novel azulene donor-acceptor materials were designed and synthesized with unique electronic effects upon protonation to generate charged species in solution. The microstructure and optical properties of these derivatives were examined to develop structure-property relationships. Studies of the microstructure of blends of charge transfer doped semiconducting polymers revealed highly ordered conductive phases in blends. The molecular packing of one blend was studied in detail using a combination of solid-state NMR and x-ray scattering revealing that dopant incorporation is unlikely to be random as assumed in transport models. Studies of the electrical properties of these highly ordered blends revealed a universal trend between the thermopower and electrical conductivity of semiconducting polymers that is independent of the doping mechanism.

  3. Molecular interactions in biomineralized hydroxyapatite amino acid modified nanoclay: In silico design of bone biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Katti, Dinesh R., E-mail: Dinesh.Katti@ndsu.edu; Sharma, Anurag; Ambre, Avinash H.; Katti, Kalpana S.

    2015-01-01

    A simulations driven approach to design of a novel biomaterial nanocomposite system is described in this study. Nanoclays modified with amino acids (OMMT) were used to mineralize hydroxyapatite (HAP), mimicking biomineralization. Representative models of organically modified montmorillonite clay (OMMT) and OMMT-hydroxyapatite (OMMT-HAP) were constructed using molecular dynamics and validated using X-ray Diffraction (XRD), Fourier Transforms Infrared (FTIR) spectroscopy and Transmission Electron Microscopy (TEM). Attractive interactions exist between Ca atoms of HAP and C=O group of aminovaleric acid, indicating chelate formation in OMMT-HAP. Interaction energy maps describe molecular interactions among different constituents and their quantitative contributions in the OMMT and OMMT-HAP systems at both parallel and perpendicular orientations. High attractive and high repulsive interactions were found between PO{sub 4}{sup 3−} and MMT clay as well as aminovaleric molecules in OMMT-HAP perpendicular and parallel models. Large non-bonded interactions in OMMT-HAP indicate influence of neighboring environment on PO{sub 4}{sup 3−} in in situ HAPclay. Extensive hydrogen bonds were observed between functional hydrogen atoms of modifier and MMT clay in OMMT-HAP as compared to OMMT. Thus, HAP interacts with clay through the aminovaleric acid. This computational study provides a framework for materials design and selection for biomaterials used in tissue engineering and other areas of regenerative medicine. - Highlights: • Representative models of a hybrid nanoclay-hydroxyapatite biomaterial are built. • Interaction energy maps are constructed using a molecular dynamics. • Quantitative interactions between the three components of the biomaterial are found. • The modeling and experimental approach provides insight into the complex nanomaterial.

  4. A distance-dependent metal-enhanced fluorescence sensing platform based on molecular beacon design.

    Science.gov (United States)

    Zhou, Zhenpeng; Huang, Hongduan; Chen, Yang; Liu, Feng; Huang, Cheng Zhi; Li, Na

    2014-02-15

    A new metal-enhanced fluorescence (MEF) based platform was developed on the basis of distance-dependent fluorescence quenching-enhancement effect, which combined the easiness of Ag-thiol chemistry with the MEF property of noble-metal structures as well as the molecular beacon design. For the given sized AgNPs, the fluorescence enhancement factor was found to increase with a d(6) dependency in agreement with fluorescence resonance energy transfer mechanism at shorter distance and decrease with a d(-3) dependency in agreement with plasmonic enhancement mechanism at longer distance between the fluorophore and the AgNP surface. As a proof of concept, the platform was demonstrated by a sensitive detection of mercuric ions, using thymine-containing molecular beacon to tune silver nanoparticle (AgNP)-enhanced fluorescence. Mercuric ions were detected via formation of a thymine-mercuric-thymine structure to open the hairpin, facilitating fluorescence recovery and AgNP enhancement to yield a limit of detection of 1 nM, which is well below the U.S. Environmental Protection Agency regulation of the Maximum Contaminant Level Goal (10nM) in drinking water. Since the AgNP functioned as not only a quencher to reduce the reagent blank signal but also an enhancement substrate to increase fluorescence of the open hairpin when target mercuric ions were present, the quenching-enhancement strategy can greatly improve the detection sensitivity and can in principle be a universal approach for various targets when combined with molecular beacon design.

  5. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Bowsher, James, E-mail: james.bowsher@duke.edu; Giles, William; Yin, Fang-Fang [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Yan, Susu [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Roper, Justin [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2014-01-15

    Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

  6. Report of the APSAC task force on attachment therapy, reactive attachment disorder, and attachment problems.

    Science.gov (United States)

    Chaffin, Mark; Hanson, Rochelle; Saunders, Benjamin E; Nichols, Todd; Barnett, Douglas; Zeanah, Charles; Berliner, Lucy; Egeland, Byron; Newman, Elana; Lyon, Tom; LeTourneau, Elizabeth; Miller-Perrin, Cindy

    2006-02-01

    Although the term attachment disorder is ambiguous, attachment therapies are increasingly used with children who are maltreated, particularly those in foster care or adoptive homes. Some children described as having attachment disorders show extreme disturbances. The needs of these children and their caretakers are real. How to meet their needs is less clear. A number of attachment-based treatment and parenting approaches purport to help children described as attachment disordered. Attachment therapy is a young and diverse field, and the benefits and risks of many treatments remain scientifically undetermined. Controversies have arisen about potentially harmful attachment therapy techniques used by a subset of attachment therapists. In this report, the Task Force reviews the controversy and makes recommendations for assessment, treatment, and practices. The report reflects American Professional Society on the Abuse of Children's (APSAC) position and also was endorsed by the American Psychological Association's Division 37 and the Division 37 Section on Child Maltreatment.

  7. Remedial Action Plan and Site Design for Stabilization of the Inactive Uranium Mill Tailings Site, Maybell, Colorado. Remedial action selection report: Attachment 2, Geology report, Final

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    The Maybell uranium mill tailings site is 25 miles (mi) (40 kilometers [km]) west of the town of Craig, Colorado, in Moffat County, in the northwestern part of the state. The unincorporated town of Maybell is 5 road mi (8 km) southwest of the site. The designated site covers approximately 110 acres (ac) (45 hectares [ha]) and consists of a concave-shaped tailings pile and rubble from the demolition of the mill buildings buried in the former mill area. Contaminated materials at the Maybell processing site include the tailings pile, which has an average depth of 20 feet (ft) (6 meters [m]) and contains 2.8 million cubic yards (yd{sup 3}) (2.1 million cubic meters [m{sup 3}]) of tailings. The former mill processing area is on the north side of the site and contains 20,000 yd{sup 3} (15,000 m{sup 3}) of contaminated demolition debris. Off-pile contamination is present and includes areas adjacent to the tailings pile, as well as contamination dispersed by wind and surface water flow. The volume of off-pile contamination to be placed in the disposal cell is 550,000 yd{sup 3} (420,000 m{sup 3}). The total volume of contaminated materials to be disposed of as part of the remedial action is estimated to be 3.37 million yd{sup 3} (2.58 million m{sup 3}). Information presented in this Final Remedial Action Plan (RAP) and referenced in supporting documents represents the current disposal cell design features and ground water compliance strategy proposed by the US Department of Energy (DOE) for the Maybell, Colorado, tailings site. Both the disposal cell design and the ground water compliance strategy have changed from those proposed prior to the preliminary final RAP document as a result of prudent site-specific technical evaluations.

  8. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Falls City, Texas. Remedial action selection report, attachment 2, geology report; attachment 3, groundwater hydrology report; and attachment 4, water resources protection strategy. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-09-01

    The uranium processing site near Falls City, Texas, was one of 24 inactive uranium mill sites designated to be remediated by the U.S. Department of Energy (DOE) under Title I of the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). The UMTRCA requires that the U.S. Nuclear Regulatory Commission (NRC) concur with the DOE`s remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the U.S. Environmental Protection Agency (EPA). The RAP, which includes this summary remedial action selection report (RAS), serves a two-fold purpose. First, it describes the activities proposed by the DOE to accomplish long-term stabilization and control of the residual radioactive materials at the inactive uranium processing site near Falls City, Texas. Second, this document and the remainder of the RAP, upon concurrence and execution by the DOE, the State of Texas, and the NRC, becomes Appendix B of the Cooperative Agreement between the DOE and the State of Texas.

  9. Design of Molecular Solar Cells via Feedback from Soft X-ray Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Himpsel, Franz J. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-12

    Spectroscopy with soft X-rays was used to develop new materials and novel designs for solar cells and artificial photosynthesis. In order to go beyond the widely-used trial-and-error approach of gradually improving a particular design, we started from the most general layout of a solar cell (or a photo-electrochemical device) and asked which classes of materials are promising for best performance. For example, the most general design of a solar cell consists of a light absorber, an electron donor, and an electron acceptor. These are characterized by four energy levels, which were measured by a combination of spectroscopic X-ray techniques. Tuning synchrotron radiation to the absorption edges of specific elements provided element- and bond-selectivity. The spectroscopic results were complemented by state-of-the-art calculations of the electronic states. These helped explaining the observed energy levels and the orbitals associated with them. The calculations were extended to a large class of materials (for example thousands of porphyrin dye complexes) in order to survey trends in the energy level structure. A few highlights serve as examples: 1) Organic molecules combining absorber, donor, and acceptor with atomic precision. 2) Exploration of highly p-doped diamond films as inert, transparent electron donors. 3) Surface-sensitive characterization of nanorod arrays used as photoanodes in water splitting. 4) Computational design of molecular complexes for efficient solar cells using two photons.

  10. Design of new inhibitors for H5N1 avian influenza using a molecular dynamics simulation

    Science.gov (United States)

    Park, Jin Woo; Jo, Won Ho

    2008-03-01

    Recently, there has been a growing interest in the treatment of H5N1 avian influenza. One of the most widely used antiviral agents is oseltamivir. However, it has been reported that oseltamivir is not as effective against the neuraminidase subtype N1 as it is against subtypes N2 and N9. In our research we addressed this problem by designing new inhibitors and these altered inhibitor's binding affinities were calculated. In this study, we introduced chemical groups to the existing oseltamivir, so to fit into the newly discovered cavity in the subtype N1. When the binding strengths of the oseltamivir and the newly designed inhibitors for N1 were calculated to examine the drug efficiency through a molecular dynamics simulation, then compared with each other, it was found that one of the designed molecules exhibited a strong binding affinity, with more than twice the binding strength than that of oseltamivir. Since the aforementioned designed inhibitor appears to have the possibility for oral activity according to the criteria of human oral bioavailability, we propose that the inhibitor is a promising antiviral drug for H5N1 avian influenza.

  11. Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design

    Science.gov (United States)

    Ishikawa, Toshihisa; Tamura, Ai; Saito, Hikaru; Wakabayashi, Kanako; Nakagawa, Hiroshi

    2005-10-01

    In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

  12. A Rational Design Strategy for the Selective Activity Enhancement of a Molecular Chaperone toward a Target Substrate.

    Science.gov (United States)

    Aprile, Francesco A; Sormanni, Pietro; Vendruscolo, Michele

    2015-08-18

    Molecular chaperones facilitate the folding and assembly of proteins and inhibit their aberrant aggregation. They thus offer several opportunities for biomedical and biotechnological applications, as for example they can often prevent protein aggregation more effectively than other therapeutic molecules, including small molecules and antibodies. Here we present a method of designing molecular chaperones with enhanced activity against specific amyloidogenic substrates while leaving unaltered their functions toward other substrates. The method consists of grafting onto a molecular chaperone a peptide designed to bind specifically an epitope in the target substrate. We illustrate this strategy by describing Hsp70 variants with increased affinities for α-synuclein and Aβ42 but otherwise unaltered affinities for other substrates. These designed variants inhibit protein aggregation and disaggregate preformed fibrils significantly more effectively than wild-type Hsp70 indicating that the strategy presented here provides a possible route for tailoring rationally molecular chaperones for specific purposes.

  13. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 2, Geology report. Revised final report

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-01

    Detailed investigations of geologic, geomorphic, and seismic conditions at the Bodo Canyon disposal site were conducted. The purpose of these investigations was basic site characterization and identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies, such as analyses of hydrologic and liquefaction hazards, used the data developed in these studies. The geomorphic analysis was employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65 kilometer radius of the site, provided the basis for seismic design parameters. The scope of work performed included the following: Compilation and analysis of previous published and unpublished geologic literature and maps; Review of historical and instrumental earthquake data; Review of site-specific subsurface geologic data, including lithologic and geophysical logs of exploratory boreholes advanced in the site area; Photogeologic interpretations of existing conventional aerial photographs; and, Ground reconnaissance and mapping of the site region.

  14. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Gunnison, Colorado. Attachment 5, Supplemental radiological data: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1992-10-01

    Diffusion coefficients for radon gas in earthen materials are required to design suitable radon-barrier covers for uranium tailings impoundments and other materials that emit radon gas. Many early measurements of radon diffusion coefficients relied on the differences in steady-state radon fluxes measured from radon source before and after installation of a cover layer of the material being tested. More recent measurements have utilized the small-sample transient (SST) technique for greater control on moistures and densities of the test soils, greater measurement precision, and reduced testing time and costs. Several of the project sites for the US Department of Energy`s Uranium Mill Tailings Remedial Action (UMTRA) Program contain radiologically contaminated subsurface material composed predominantly of cobbles, gravels andsands. Since remedial action designs require radon diffusion coefficients for the source materials as well as the cover materials, these cobbly and gravelly materials also must be tested. This report contains the following information: a description of the test materials used and the methods developed to conduct the SST radon diffusion measurements on cobbly soils; the protocol for conducting radon diffusion tests oncobbly soils; the results of measurements on the test samples; and modifications to the FITS computer code for analyzing the time-dependent radon diffusion data.

  15. Remedial Action Plan and Site design for stabilization of the inactive Uranium Mill Tailings sites at Slick Rock, Colorado: Revision 1. Remedial action selection report, Attachment 2, geology report, Attachment 3, ground water hydrology report, Attachment 4, water resources protection strategy. Final

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    The Slick Rock uranium mill tailings sites are located near the small community of Slick Rock, in San Miguel County, Colorado. There are two designated Uranium Mill Tailings Remedial Action (UMTRA) Project sites at Slick Rock: the Union Carbide site and the North Continent site. Both sites are adjacent to the Dolores River. The sites contain former mill building concrete foundations, tailings piles, demolition debris, and areas contaminated by windblown and waterborne radioactive materials. The total estimated volume of contaminated materials is approximately 621,000 cubic yards (475,000 cubic meters). In addition to the contamination at the two processing site areas, 13 vicinity properties were contaminated. Contamination associated with the UC and NC sites has leached into ground water. Pursuant to the requirements of the Uranium Mill Tailings Radiation Control Act (UMTRCA) (42 USC {section}7901 et seq.), the proposed remedial action plan (RAP) will satisfy the final US Environmental Protection Agency (EPA) standards in 40 CFR Part 192 (60 FR 2854) for cleanup, stabilization, and control of the residual radioactive material (RRM) (tailings and other contaminated materials) at the disposal site at Burro Canyon. The requirements for control of the RRM (Subpart A) will be satisfied by the construction of an engineered disposal cell. The proposed remedial action will consist of relocating the uranium mill tailings, contaminated vicinity property materials, demolition debris, and windblown/weaterborne materials to a permanent repository at the Burro Canyon disposal site. The site is approximately 5 road mi (8 km) northeast of the mill sites on land recently transferred to the DOE by the Bureau of Land Management.

  16. A strategy of designing the ligand of antibody affinity chromatography based on molecular dynamics simulation.

    Science.gov (United States)

    Dai, Lu; Li, Weikang; Sun, Fei; Li, Baizhi; Li, Hongrui; Zhang, Hongxing; Zheng, Qingchuan; Liang, Chongyang

    2016-09-01

    Designing affinity ligands has always been the development focus of affinity chromatography. Previous antibody affinity ligand designs were mostly based on the crystal structure of protein A (UniProt code number: P38507), and the antibody-binding domains were modified according to the properties of amino acid residues. Currently, more effective bioinformatic prediction and experimental validation has been used to improve the design of antibody affinity ligands. In the present study, the complex crystal structure (the domain D of protein A and the Fab segment of IgM, PDB code: 1DEE) was used as the model. The vital site that inhibits the binding between domain D and IgM was estimated by means of molecular dynamics (MD) simulation, then MM-GBSA calculations were used to design a mutant of domain D (K46E) for improving affinity on the above vital site. The binding analysis using Biacore showed the association and dissociation parameters of K46E mutant that were optimized with IgM. The affinity increase of K46E mutant preferred for IgM, the affinity order is K46E tetramer (KD=6.02×10(-9)M)>K46E mutant (KD=6.66×10(-8)M)>domain D (KD=2.17×10(-7)M). Similar results were obtained when the optimized ligands were immobilized to the chromatography medium. A complete designing strategy was validated in this study, which will provide a novel insight into designing new ligands of antibody affinity chromatography media.

  17. Attachment is a dynamic system

    Directory of Open Access Journals (Sweden)

    Zlatka Cugmas

    2003-04-01

    Full Text Available On the basis of the study of recent scientific literature about the development of attachment, the author answers the following questions: which are the postulates the theory of attachment has about the stability of the patterns of attachment, which level of stability in the patterns of attachment from infancy to adulthood these studies illuminate and which factors significantly influence the (instability of the patterns of attachment in time. The theory of attachment assumes that normal circumstances elicit stability. Changes, however, can be the result of important events influencing the sensitivity of the object of attachment. Agreement has not yet been reached regarding the percentage of stability in the patterns of attachment. There is more agreement regarding attachment in adulthood than that in childhood. The results depend on the size and characteristics of the subjects of the research, the measuring instruments, type of data analysis etc. The author concludes that attachment is a dynamic system influenced by significant changes in life (the cognitive development of the child, external care, parents' divorce, different stressful situations. As the influence of stressful events on the individual person' s quality of attachment is examined, it is necessary to consider also his/her temperamental characteristics, role of other people in their lives, etc.

  18. Attachment Theory in Tourism

    Directory of Open Access Journals (Sweden)

    Maximiliano Korstanje

    2007-01-01

    Full Text Available The following work is intended to a revision on attachment theory. The postulates of the theory of the sure base point that the system of exploration meets in narrow relation the system of conducts of attachment and the figure of the keepers. The conducts that characterize and symbolize the relation of the adult with the environment are carried back to the early age, in the moment in which the child develops the affective capacity. What difference does exist between someone who decides to journey to England and that one that one decides to travel to Mar del Plata? How it is possible to study this topic of on a manner trustworthy? These three questions were key to begin the investigation. Nevertheless, the matter began to find certain limitations linked to the methodology that had to be in use. It is possible to use careless they on the leisure scope, a theory which still demonstrates certain inconsistencies in its own clinical application?

  19. DMB-375S电机轴螺旋键槽铣胎的改进设计%Improved Design of Double Sprial Keyways Milling Attachment of Type DMB-375S Motor Shaft

    Institute of Scientific and Technical Information of China (English)

    冯革

    2001-01-01

    DMB-375S电机轴铁芯键槽为大导程双螺旋键槽。在立式铣床上使用靠模胎具加工。胎具存在刚性差、精度低、操作不便的问题。为了提高加工精度和生产效率,对原胎具进行改进设计,采用挂轮进给、分度头旋转的运动方式进行铣削。分析FW160型分度头的传动系统图,得出分度头的定数取决于1:40的蜗轮传动,其它的均为1:1传动,如将1:1的螺旋齿轮传动改为蜗轮蜗杆传动即可大大提高分度头的定数,从而实现大导程螺旋键槽的加工。该胎具具有刚性好、精度高、操作简便的优点,选择适当的挂轮还可扩展其加工范围。%The keyways of the motor shaft of type DMB- 375S are two longpitch spir al slots.They are produced with profiling attachment in vertical miller.But the atta chment has some problems such as poor rigidity,low precision and hard to be used. For improving working precision and efficiency,The original attachment was redesigned, cutting with gear feed and graduator rot ation. According to the c alculating result of gears rate,this method is available since its few t ransmission links and compact structure.Analysing the transmission system drawwi ng of type FW160 graduator, we can easily know that its rate is depends on worm ge ars ra te 1:40,and other's is 1:1.If the helix gears with rate 1:1 can be changed to wo rm g ears,the rate of graduator will be increased greatly.So the long pitch keyways c an be worked out.The attachment designed in this new method has good rigidity, high precision, an d is easy to be operated. If to use the suitable gear change, its working range can be expanded.

  20. Parental incarceration, attachment and child psychopathology.

    Science.gov (United States)

    Murray, Joseph; Murray, Lynne

    2010-07-01

    Theory and evidence relating parental incarceration, attachment, and psychopathology are reviewed. Parental incarceration is a strong risk factor for long-lasting psychopathology, including antisocial and internalizing outcomes. Parental incarceration might threaten children's attachment security because of parent-child separation, confusing communication about parental absence, restricted contact with incarcerated parents, and unstable caregiving arrangements. Parental incarceration can also cause economic strain, reduced supervision, stigma, home and school moves, and other negative life events for children. Thus, there are multiple possible mechanisms whereby parental incarceration might increase risk for child psychopathology. Maternal incarceration tends to cause more disruption for children than paternal incarceration and may lead to greater risk for insecure attachment and psychopathology. Children's prior attachment relations and other life experiences are likely to be of great importance for understanding children's reactions to parental incarceration. Several hypotheses are presented about how prior insecure attachment and social adversity might interact with parental incarceration and contribute to psychopathology. Carefully designed longitudinal studies, randomized controlled trials, and cross-national comparative research are required to test these hypotheses.

  1. Improved Attachment in a Hybrid Inflatable Pressure Vessel

    Science.gov (United States)

    Johnson, Christopher J.; Patterson, Ross; Spexarth, Gary R.

    2010-01-01

    The vessel is a hybrid that comprises an inflatable shell attached to a rigid structure. The inflatable shell is, itself, a hybrid that comprises (1) a pressure bladder restrained against expansion by (2) a restraint layer that comprises a web of straps made from high-strength polymeric fabrics. The present improvements are intended to overcome deficiencies in those aspects of the original design that pertain to attachment of the inflatable shell to the rigid structure. In a typical intended application, such attachment(s) would be made at one or more window or hatch frames to incorporate the windows or hatches as integral parts of the overall vessel.

  2. Probing the molecular design of hyper-branched aryl polyesters towards lubricant applications.

    Science.gov (United States)

    Robinson, Joshua W; Zhou, Yan; Bhattacharya, Priyanka; Erck, Robert; Qu, Jun; Bays, J Timothy; Cosimbescu, Lelia

    2016-01-01

    We report novel polymeric materials that may be used as viscosity index improvers (VII) for lubricant applications. Our efforts included probing the comb-burst hyper-branched aryl polyester architecture for beneficial viscosity and friction behavior when utilized as an additive in a group I oil. The monomer was designed as to undergo polymerization via polycondensation within the architectural construct (AB2), typical of hyperbranched polymers. The monomer design was comprised of aliphatic arms (12 or 16 methylenes) to provide the necessary lipophilicity to achieve solubility in a non-polar medium. Once polymerized, via catalyst and heat, the surface alcohols were functionalized with fatty acids (lauric and palmitic). Controlling the aliphatic nature of the internal arms and peripheral end-groups provided four unique flexible polymer designs. Changing the reaction time and concentration provided opportunities to investigate the influence of molecular weight and branching density on oil-solubility, viscosity, and friction. Oil-solubility was found to decrease with fewer internal carbons, but the number of internal carbons appears to have little influence on the bulk solution viscosity. At concentrations of 2 wt % in a group I base oil, these polymer additives demonstrated an improved viscosity index and reduced friction coefficient, validating the basic approach.

  3. Probing the molecular design of hyper-branched aryl polyesters towards lubricant applications

    Science.gov (United States)

    Robinson, Joshua W.; Zhou, Yan; Bhattacharya, Priyanka; Erck, Robert; Qu, Jun; Bays, J. Timothy; Cosimbescu, Lelia

    2016-01-01

    We report novel polymeric materials that may be used as viscosity index improvers (VII) for lubricant applications. Our efforts included probing the comb-burst hyper-branched aryl polyester architecture for beneficial viscosity and friction behavior when utilized as an additive in a group I oil. The monomer was designed as to undergo polymerization via polycondensation within the architectural construct (AB2), typical of hyperbranched polymers. The monomer design was comprised of aliphatic arms (12 or 16 methylenes) to provide the necessary lipophilicity to achieve solubility in a non-polar medium. Once polymerized, via catalyst and heat, the surface alcohols were functionalized with fatty acids (lauric and palmitic). Controlling the aliphatic nature of the internal arms and peripheral end-groups provided four unique flexible polymer designs. Changing the reaction time and concentration provided opportunities to investigate the influence of molecular weight and branching density on oil-solubility, viscosity, and friction. Oil-solubility was found to decrease with fewer internal carbons, but the number of internal carbons appears to have little influence on the bulk solution viscosity. At concentrations of 2 wt % in a group I base oil, these polymer additives demonstrated an improved viscosity index and reduced friction coefficient, validating the basic approach.

  4. Custom-Designed Molecular Scissors for Site-Specific Manipulation of the Plant and Mammalian Genomes

    Science.gov (United States)

    Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

    Zinc finger nucleases (ZFNs) are custom-designed molecular scissors, engineered to cut at specific DNA sequences. ZFNs combine the zinc finger proteins (ZFPs) with the nonspecific cleavage domain of the FokI restriction enzyme. The DNA-binding specificity of ZFNs can be easily altered experimentally. This easy manipulation of the ZFN recognition specificity enables one to deliver a targeted double-strand break (DSB) to a genome. The targeted DSB stimulates local gene targeting by several orders of magnitude at that specific cut site via homologous recombination (HR). Thus, ZFNs have become an important experimental tool to make site-specific and permanent alterations to genomes of not only plants and mammals but also of many other organisms. Engineering of custom ZFNs involves many steps. The first step is to identify a ZFN site at or near the chosen chromosomal target within the genome to which ZFNs will bind and cut. The second step is to design and/or select various ZFP combinations that will bind to the chosen target site with high specificity and affinity. The DNA coding sequence for the designed ZFPs are then assembled by polymerase chain reaction (PCR) using oligonucleotides. The third step is to fuse the ZFP constructs to the FokI cleavage domain. The ZFNs are then expressed as proteins by using the rabbit reticulocyte in vitro transcription/translation system and the protein products assayed for their DNA cleavage specificity.

  5. Design of biomimetic catalysts by molecular imprinting in synthetic polymers: the role of transition state stabilization.

    Science.gov (United States)

    Wulff, Günter; Liu, Junqiu

    2012-02-21

    The impressive efficiency and selectivity of biological catalysts has engendered a long-standing effort to understand the details of enzyme action. It is widely accepted that enzymes accelerate reactions through their steric and electronic complementarity to the reactants in the rate-determining transition states. Thus, tight binding to the transition state of a reactant (rather than to the corresponding substrate) lowers the activation energy of the reaction, providing strong catalytic activity. Debates concerning the fundamentals of enzyme catalysis continue, however, and non-natural enzyme mimics offer important additional insight in this area. Molecular structures that mimic enzymes through the design of a predetermined binding site that stabilizes the transition state of a desired reaction are invaluable in this regard. Catalytic antibodies, which can be quite active when raised against stable transition state analogues of the corresponding reaction, represent particularly successful examples. Recently, synthetic chemistry has begun to match nature's ability to produce antibody-like binding sites with high affinities for the transition state. Thus, synthetic, molecularly imprinted polymers have been engineered to provide enzyme-like specificity and activity, and they now represent a powerful tool for creating highly efficient catalysts. In this Account, we review recent efforts to develop enzyme models through the concept of transition state stabilization. In particular, models for carboxypeptidase A were prepared through the molecular imprinting of synthetic polymers. On the basis of successful experiments with phosphonic esters as templates to arrange amidinium groups in the active site, the method was further improved by combining the concept of transition state stabilization with the introduction of special catalytic moieties, such as metal ions in a defined orientation in the active site. In this way, the imprinted polymers were able to provide both an

  6. Molecular origins of optoelectronic properties in coumarin dyes: toward designer solar cell and laser applications.

    Science.gov (United States)

    Liu, Xiaogang; Cole, Jacqueline M; Waddell, Paul G; Lin, Tze-Chia; Radia, Jignesh; Zeidler, Anita

    2012-01-12

    Coumarin derivatives are used in a wide range of applications, such as dye-sensitized solar cells (DSCs) and dye lasers, and have therefore attracted considerable research interest. In order to understand the molecular origins of their optoelectronic properties, molecular structures for 29 coumarin laser dyes are statistically analyzed. To this end, data for 25 compounds were taken from the Cambridge Structural Database and compared with data for four new crystal structures of coumarin laser dyes [Coumarin 487 (C(19)H(23)NO(2)), Coumarin 498 (C(16)H(17)NO(4)S), Coumarin 510 (C(20)H(18)N(2)O(2)), and Coumarin 525 (C(22)H(18)N(2)O(3))], which are reported herein. The competing contributions of different resonance states to the bond lengths of the 4- and 7-substituted coumarin laser dyes are computed based on the harmonic oscillator stabilization energy model. Consequently, a positive correlation between the contribution of the para-quinoidal resonance state and the UV-vis peak absorption wavelength of these coumarins is revealed. Furthermore, the perturbations of optoelectronic properties, owing to chemical substituents in these coumarin laser dyes, are analyzed: it is found that their UV-vis peak absorption and lasing wavelengths experience a red shift, as the electron-donating strength of the 7-position substituent increases and/or the electron-withdrawing strength of the 3- or 4-position substituent rises; this conclusion is corroborated by quantum-chemical calculations. It is also revealed that the closer the relevant substituents align with the direction of the intramolecular charge transfer (ICT), the larger the spectral shifts and the higher the molar extinction coefficients of coumarin laser dyes. These findings are important for understanding the ICT mechanism in coumarins. Meanwhile, all structure-property correlations revealed herein will enable knowledge-based molecular design of coumarins for dye lasers and DSC applications.

  7. Design of potentially active ligands for SH2 domains by molecular modeling methods

    Directory of Open Access Journals (Sweden)

    Hurmach V. V.

    2014-07-01

    Full Text Available Search for new chemical structures possessing specific biological activity is a complex problem that needs the use of the latest achievements of molecular modeling technologies. It is well known that SH2 domains play a major role in ontogenesis as intermediaries of specific protein-protein interactions. Aim. Developing an algorithm to investigate the properties of SH2 domain binding, search for new potential active compounds for the whole SH2 domains class. Methods. In this paper, we utilize a complex of computer modeling methods to create a generic set of potentially active compounds targeting universally at the whole class of SH2 domains. A cluster analysis of all available three-dimensional structures of SH2 domains was performed and general pharmacophore models were formulated. The models were used for virtual screening of collection of drug-like compounds provided by Enamine Ltd. Results. The design technique for library of potentially active compounds for SH2 domains class was proposed. Conclusions. The original algorithm of SH2 domains research with molecular docking method was developed. Using our algorithm, the active compounds for SH2 domains were found.

  8. When biomolecules meet graphene: from molecular level interactions to material design and applications.

    Science.gov (United States)

    Li, Dapeng; Zhang, Wensi; Yu, Xiaoqing; Wang, Zhenping; Su, Zhiqiang; Wei, Gang

    2016-12-01

    Graphene-based materials have attracted increasing attention due to their atomically-thick two-dimensional structures, high conductivity, excellent mechanical properties, and large specific surface areas. The combination of biomolecules with graphene-based materials offers a promising method to fabricate novel graphene-biomolecule hybrid nanomaterials with unique functions in biology, medicine, nanotechnology, and materials science. In this review, we focus on a summarization of the recent studies in functionalizing graphene-based materials using different biomolecules, such as DNA, peptides, proteins, enzymes, carbohydrates, and viruses. The different interactions between graphene and biomolecules at the molecular level are demonstrated and discussed in detail. In addition, the potential applications of the created graphene-biomolecule nanohybrids in drug delivery, cancer treatment, tissue engineering, biosensors, bioimaging, energy materials, and other nanotechnological applications are presented. This review will be helpful to know the modification of graphene with biomolecules, understand the interactions between graphene and biomolecules at the molecular level, and design functional graphene-based nanomaterials with unique properties for various applications.

  9. Molecular design, synthesis and physical properties of novel Cytisine-derivatives - Experimental and theoretical study

    Science.gov (United States)

    Ivanova, Bojidarka; Spiteller, Michael

    2013-02-01

    The paper presented a comprehensive theoretical and experimental study on the molecular drugs-design, synthesis, isolation, physical spectroscopic and mass spectrometric elucidation of novel functionalization derivatives of Cytisine (Cyt), using nucleosidic residues. Since these alkaloids have established biochemical profile, related the binding affinity of the nicotinic acetylcholine receptors (nAChRs), particularly α7 sub-type, the presented correlation between the molecular structure and properties allowed to evaluated the highlights of the biochemical hypothesises related the Schizophrenia. The anticancer activity of α7 subtype agonists and the crucial role of the nucleoside-based medications in the cancer therapy provided opportunity for further study on the biochemical relationship between Schizophrenia and few kinds of cancers, which has been hypothesized recently. The physical electronic absorptions (EAs), circular dichroic (CD) and Raman spectroscopic (RS) properties as well as mass spectrometric (MS) data, obtained using electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) methods under the positive single (MS) and tandem (MS/MS) modes of operation are discussed. Taking into account reports on a fatal intoxication of Cyt, the presented data would be of interest in the field of forensic chemistry, through development of highly selective and sensitive analytical protocols. Quantum chemical method is used to predict the physical properties of the isolated alkaloids, their affinity to the receptor loop and gas-phase stabilized species, observed mass spectrometrically.

  10. Which strategy for molecular probe design? An answer from the integration of spectroscopy and QM modeling.

    Science.gov (United States)

    Marini, Alberto; Muñoz-Losa, Aurora; Pucci, Andrea; Ruggeri, Giacomo; Mennucci, Benedetta

    2010-08-21

    With this study we show that the maturity reached by quantum-mechanical (QM) modeling has allowed a new analytical approach to the design of molecular probes. In this approach, the strategy is to integrate suited computational tools with multi-spectroscopic measurements to identify specific signals for the characterization of the molecular probe with respect to the perturbation used and the environmental conditions applied. The application of the strategy to a typical optical probe (2-acetylanthracene) has allowed the identification of specific IR and NMR signals for the characterization of the conformational states in both solid and solution states. This analysis has been successively extended to the investigation of specific optical signals. In particular we have shown that the introduction of a substituent in specific positions of the aromatic structure induces a different perturbation in the different excited states of the precursor anthracene with consequent differentiations of the states with respect to their solvent sensitivity (both in terms of bulk and specific effects). Finally, the integration of simulated and experimental emission spectra has revealed a possible isomerization in the excited state with resulting change of the conformational state in the absorbing and the emitting species.

  11. Computer-aided molecular design of solvents for accelerated reaction kinetics.

    Science.gov (United States)

    Struebing, Heiko; Ganase, Zara; Karamertzanis, Panagiotis G; Siougkrou, Eirini; Haycock, Peter; Piccione, Patrick M; Armstrong, Alan; Galindo, Amparo; Adjiman, Claire S

    2013-11-01

    Solvents can significantly alter the rates and selectivity of liquid-phase organic reactions, often hindering the development of new synthetic routes or, if chosen wisely, facilitating routes by improving rates and selectivities. To address this challenge, a systematic methodology is proposed that quickly identifies improved reaction solvents by combining quantum mechanical computations of the reaction rate constant in a few solvents with a computer-aided molecular design (CAMD) procedure. The approach allows the identification of a high-performance solvent within a very large set of possible molecules. The validity of our CAMD approach is demonstrated through application to a classical nucleophilic substitution reaction for the study of solvent effects, the Menschutkin reaction. The results were validated successfully by in situ kinetic experiments. A space of 1,341 solvents was explored in silico, but required quantum-mechanical calculations of the rate constant in only nine solvents, and uncovered a solvent that increases the rate constant by 40%.

  12. Development of a Confocal Optical System Design for Molecular Imaging Applications of Biochip

    Directory of Open Access Journals (Sweden)

    Guoliang Huang

    2007-01-01

    Full Text Available A novel confocal optical system design and a dual laser confocal scanner have been developed to meet the requirements of highly sensitive detection of biomolecules on microarray chips, which is characterized by a long working distance (wd>3.0 mm, high numerical aperture (NA=0.72, and only 3 materials and 7 lenses used. This confocal optical system has a high scanning resolution, an excellent contrast and signal-to-noise ratio, and an efficiency of collected fluorescence of more than 2-fold better than that of other commercial confocal biochip scanners. The scanner is as equally good for the molecular imaging detection of enclosed biochips as for the detection of biological samples on a slide surface covered with a cover-slip glass. Some applications of gene and protein imagings using the dual laser confocal scanner are described.

  13. Molecular design and ordering effects in π-functional materials for transistor and solar cell applications

    KAUST Repository

    Beaujuge, Pierre

    2011-12-21

    Organic electronics are broadly anticipated to impact the development of flexible thin-film device technologies. Among these, solution-processable π-conjugated polymers and small molecules are proving particularly promising in field-effect transistors and bulk heterojunction solar cells. This Perspective analyzes some of the most exciting strategies recently suggested in the design and structural organization of π-functional materials for transistor and solar cell applications. Emphasis is placed on the interplay between molecular structure, self-assembling properties, nanoscale and mesoscale ordering, and device efficiency parameters. A critical look at the various approaches used to optimize both materials and device performance is provided to assist in the identification of new directions and further advances. © 2011 American Chemical Society.

  14. Principles and design of a Zeeman-Sisyphus decelerator for molecular beams

    CERN Document Server

    Fitch, N J

    2016-01-01

    We explore a technique for decelerating molecules using a static magnetic field and optical pumping. Molecules travel through a spatially varying magnetic field and are repeatedly pumped into a weak-field seeking state as they move towards each strong field region, and into a strong-field seeking state as they move towards weak field. The method is time-independent and so is suitable for decelerating both pulsed and continuous molecular beams. By using guiding magnets at each weak field region, the beam can be simultaneously guided and decelerated. By tapering the magnetic field strength in the strong field regions, and exploiting the Doppler shift, the velocity distribution can be compressed during deceleration. We develop the principles of this deceleration technique, provide a realistic design, use numerical simulations to evaluate its performance for a beam of CaF, and compare this performance to other deceleration methods.

  15. Lessons from Nature: A Bio-Inspired Approach to Molecular Design.

    Science.gov (United States)

    Cook, Sarah A; Hill, Ethan A; Borovik, A S

    2015-07-14

    Metalloproteins contain actives sites with intricate structures that perform specific functions with high selectivity and efficiency. The complexity of these systems complicates the study of their function and the understanding of the properties that give rise to their reactivity. One approach that has contributed to the current level of understanding of their biological function is the study of synthetic constructs that mimic one or more aspects of the native metalloproteins. These systems allow individual contributions to the structure and function to be analyzed and also permit spectroscopic characterization of the metal cofactors without complications from the protein environment. This Current Topic is a review of synthetic constructs as probes for understanding the biological activation of small molecules. These topics are developed from the perspective of seminal molecular design breakthroughs from the past that provide the foundation for the systems used today.

  16. Design, preparation, surface recognition properties, and characteristics of icariin molecularly imprinted polymers

    Directory of Open Access Journals (Sweden)

    Xiaohe Jia

    2015-12-01

    Full Text Available Icariin molecularly imprinted polymers (MIPs were prepared by precipitation polymerization. Prior to the polymerization, computer simulation was performed to sketchily choose the suitable functional monomer and the corresponding polymerization solvent. The optimized synthesis parameters, including the functional monomer acrylamide, the mixture of methanol and acetonitrile (V:V = 3:1 as the polymerization solvent, and the reaction molar ratio (1:6:80 of template molecule, functional monomer and cross-linker, were respectively obtained by single factor analysis and orthogonal design methods. The results of the adsorption experiments showed that the resultant MIPs exhibited good adsorption and recognition abilities to icariin. Scatchard analysis illustrated that the homogeneous binding sites only for icariin molecules were formed in the prepared MIPs.

  17. Molecular design principles underlying β-strand swapping in the adhesive dimerization of cadherins.

    Science.gov (United States)

    Vendome, Jeremie; Posy, Shoshana; Jin, Xiangshu; Bahna, Fabiana; Ahlsen, Goran; Shapiro, Lawrence; Honig, Barry

    2011-06-01

    Cell adhesion by classical cadherins is mediated by dimerization of their EC1 domains through the 'swapping' of N-terminal β-strands. We use molecular simulations, measurements of binding affinities and X-ray crystallography to provide a detailed picture of the structural and energetic factors that control the adhesive dimerization of cadherins. We show that strand swapping in EC1 is driven by conformational strain in cadherin monomers that arises from the anchoring of their short N-terminal strand at one end by the conserved Trp2 and at the other by ligation to Ca(2+) ions. We also demonstrate that a conserved proline-proline motif functions to avoid the formation of an overly tight interface where affinity differences between different cadherins, crucial at the cellular level, are lost. We use these findings to design site-directed mutations that transform a monomeric EC2-EC3 domain cadherin construct into a strand-swapped dimer.

  18. An integrated molecular modeling approach for in silico design of new tetracyclic derivatives as ALK inhibitors.

    Science.gov (United States)

    Peddi, Saikiran Reddy; Sivan, Sree Kanth; Manga, Vijjulatha

    2016-10-01

    Anaplastic lymphoma kinase (ALK), a promising therapeutic target for treatment of human cancers, is a receptor tyrosine kinase that instigates the activation of several signal transduction pathways. In the present study, in silico methods have been employed in order to explore the structural features and functionalities of a series of tetracyclic derivatives displaying potent inhibitory activity toward ALK. Initially docking was performed using GLIDE 5.6 to probe the bioactive conformation of all the compounds and to understand the binding modes of inhibitors. The docking results revealed that ligand interaction with Met 1199 plays a crucial role in binding of inhibitors to ALK. Further to establish a robust 3D-QSAR model using CoMFA and CoMSIA methods, the whole dataset was divided into three splits. Model obtained from Split 3 showed high accuracy ([Formula: see text] of 0.700 and 0.682, [Formula: see text] of 0.971 and 0.974, [Formula: see text] of 0.673 and 0.811, respectively for CoMFA and CoMSIA). The key structural requirements for enhancing the inhibitory activity were derived from CoMFA and CoMSIA contours in combination with site map analysis. Substituting small electronegative groups at Position 8 by replacing either morpholine or piperidine rings and maintaining hydrophobic character at Position 9 in tetracyclic derivatives can enhance the inhibitory potential. Finally, we performed molecular dynamics simulations in order to investigate the stability of protein ligand interactions and MM/GBSA calculations to compare binding free energies of co-crystal ligand and newly designed molecule N1. Based on the coherence of outcome of various molecular modeling studies, a set of 11 new molecules having potential predicted inhibitory activity were designed.

  19. Host-guest interaction and structural ordering in polymeric nanoassemblies: Influence of molecular design.

    Science.gov (United States)

    Antoniuk, Iurii; Plazzotta, Beatrice; Wintgens, Véronique; Volet, Gisèle; Nielsen, Thorbjørn T; Pedersen, Jan Skov; Amiel, Catherine

    2017-02-24

    Host-guest nanoassemblies made from spontaneous self-association of host and guest polymers in aqueous solutions have been studied. The specific motivation behind this work was to clarify the impact of the molecular design of the polymers on the interactions between them and on the inner structure of the resulting nanoassemblies. The polymers were composed of a dextran backbone, functionalized with either pendant β-cyclodextrin (CD) or adamantyl (Ada). Those groups were connected to the backbone either directly or with hydrophilic polyethylene glycol (PEG) spacers. To study the impact of those spacers we have proposed a synthetic pathway to new guest polymers. The latter relied on the use of thiol-substituted dextrans as a scaffold, which is subsequently transformed into PEG-Ada grafted guest polymers via nucleophile-mediated thiol-click reaction. Surface plasmon resonance (SPR) studies evidenced strong mutual affinities between the host and guest polymers and showed that the stoichiometry was close to the ideal one (CD/Ada = 1/1) when PEG spacers were introduced. The structure of the nanoassemblies was studied by a combination of dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). The nature of the individual host or guest polymers has a strong impact on the size and internal structure of the resulting nanoassemblies. The presence of PEG spacers in the polymers led to smaller and less compact nanoassemblies, as evidenced by their large correlation length values (4-20nm compared to 2nm without PEG spacers). At the same time, all types of nanoassemblies appear to have radial density distribution with denser cores and pending polymer chains at the periphery. This study, centered on the influence of the molecular design on the host-guest interactions and structural ordering in polymeric nanoassemblies, will help to tailor host-guest nanoassemblies with attractive drug delivery profiles.

  20. Molecular modeling study for inhibition mechanism of human chymase and its application in inhibitor design.

    Directory of Open Access Journals (Sweden)

    Mahreen Arooj

    Full Text Available Human chymase catalyzes the hydrolysis of peptide bonds. Three chymase inhibitors with very similar chemical structures but highly different inhibitory profiles towards the hydrolase function of chymase were selected with the aim of elucidating the origin of disparities in their biological activities. As a substrate (angiotensin-I bound crystal structure is not available, molecular docking was performed to dock the substrate into the active site. Molecular dynamics simulations of chymase complexes with inhibitors and substrate were performed to calculate the binding orientation of inhibitors and substrate as well as to characterize conformational changes in the active site. The results elucidate details of the 3D chymase structure as well as the importance of K40 in hydrolase function. Binding mode analysis showed that substitution of a heavier Cl atom at the phenyl ring of most active inhibitor produced a great deal of variation in its orientation causing the phosphinate group to interact strongly with residue K40. Dynamics simulations revealed the conformational variation in region of V36-F41 upon substrate and inhibitor binding induced a shift in the location of K40 thus changing its interactions with them. Chymase complexes with the most active compound and substrate were used for development of a hybrid pharmacophore model which was applied in databases screening. Finally, hits which bound well at the active site, exhibited key interactions and favorable electronic properties were identified as possible inhibitors for chymase. This study not only elucidates inhibitory mechanism of chymase inhibitors but also provides key structural insights which will aid in the rational design of novel potent inhibitors of the enzyme. In general, the strategy applied in the current study could be a promising computational approach and may be generally applicable to drug design for other enzymes.

  1. The Child Attachment Interview: A Narrative Review

    Science.gov (United States)

    Privizzini, Antonella

    2017-01-01

    Attachment theory promoted an impressive body of research on the psychic developmental processes, resulting in studies on both typical and atypical development. Much of the diffusion of the attachment theory in the clinical field was related to the design of reliable instruments to evaluate the organization of attachment in infancy as well as in adulthood. Until recently, the lack of a suitable instrument to assess attachment in middle childhood as well as in adolescence hindered the expansion of research in these developmental phases during which the parent-child relationship takes on a different, albeit still crucial, role. The Child Attachment Interview (CAI), a measure that was recently designed to assess attachment at a representational level in middle childhood and adolescence, filled the measurement gap. The aim of the current review was to summarize previous empirical investigations concerning CAI in order to (a) provide an overview of the state of current research, (b) identify unanswered questions, and (c) propose future research directions. A narrative review was conducted to map the current research findings by searching for the term “Child Attachment Interview” in the Medline, Scopus, Web of Science, and PsychINFO databases, followed by a search in Mendeley. Limits were set to exclude dissertations, chapters in books, and qualitative or theoretical papers, while empirical studies were included if they used the CAI and were published in English language, peer-reviewed journals by July, 2016. The review, which ultimately included 39 studies meeting the criteria, showed that the CAI is a reliable instrument to assess attachment organization in clinical and non-clinical samples, thus providing a worthwhile contribution to the investigation of the influence of the parent-child relationship beyond infancy and early childhood. Nevertheless, the review pointed out a number of relevant open issues, the most critical of which concerned the CAI coding and

  2. The Child Attachment Interview: A Narrative Review.

    Science.gov (United States)

    Privizzini, Antonella

    2017-01-01

    Attachment theory promoted an impressive body of research on the psychic developmental processes, resulting in studies on both typical and atypical development. Much of the diffusion of the attachment theory in the clinical field was related to the design of reliable instruments to evaluate the organization of attachment in infancy as well as in adulthood. Until recently, the lack of a suitable instrument to assess attachment in middle childhood as well as in adolescence hindered the expansion of research in these developmental phases during which the parent-child relationship takes on a different, albeit still crucial, role. The Child Attachment Interview (CAI), a measure that was recently designed to assess attachment at a representational level in middle childhood and adolescence, filled the measurement gap. The aim of the current review was to summarize previous empirical investigations concerning CAI in order to (a) provide an overview of the state of current research, (b) identify unanswered questions, and (c) propose future research directions. A narrative review was conducted to map the current research findings by searching for the term "Child Attachment Interview" in the Medline, Scopus, Web of Science, and PsychINFO databases, followed by a search in Mendeley. Limits were set to exclude dissertations, chapters in books, and qualitative or theoretical papers, while empirical studies were included if they used the CAI and were published in English language, peer-reviewed journals by July, 2016. The review, which ultimately included 39 studies meeting the criteria, showed that the CAI is a reliable instrument to assess attachment organization in clinical and non-clinical samples, thus providing a worthwhile contribution to the investigation of the influence of the parent-child relationship beyond infancy and early childhood. Nevertheless, the review pointed out a number of relevant open issues, the most critical of which concerned the CAI coding and

  3. Synthesis, Structure and Reactivity of Molecules Attached to Electrode Surfaces.

    Science.gov (United States)

    2014-09-26

    Structure and Reactivity of Molecules Attached to Electrode Surfaces", AFOSR #81-0149 III. REPORTING PERIOD: April 15, 1981 through April 14, 1985 IV...Adsorption .... ............... 17 9. Effect of Surface Roughness on Adsorbate Orientation and Reactivity . 20 10. Ordered/ Disordered Packing in Chemisorbed... reactivity only when present in the edge-pendant orientation. Clearly, molecular orientation (i.e., mode of +. .4 o,, -12- attachment to the surface) is a

  4. Borderline disorder and attachment pathology.

    Science.gov (United States)

    West, M; Keller, A; Links, P; Patrick, J

    1993-02-01

    In this paper, the authors investigate the theoretical and empirical association between dysfunctions of the attachment system and borderline personality disorder. Attachment theory focuses on the maintenance of a sense of safety and security through a close personal relationship with a particular person. Based on a biological behavioural system, functional attachment relationships in adulthood rely on experiences and expectations of security within the relationship. These issues are also important to the definition and dynamics of borderline personality disorder. The dimensions and patterns of reciprocal attachment were compared with other scales measuring components of psychopathology and interpersonal relationships. In a sample of 85 female outpatients, only four of the attachment scales--feared loss, secure base, compulsive care-seeking and angry withdrawal--identified patients with high scores on a measure of borderline disorder. Of these four scales, feared loss had the predominant effect. These empirical results support the hypothesized relationship between dysfunctions of the attachment system and borderline disorder.

  5. Sentence-Level Attachment Prediction

    Science.gov (United States)

    Albakour, M.-Dyaa; Kruschwitz, Udo; Lucas, Simon

    Attachment prediction is the task of automatically identifying email messages that should contain an attachment. This can be useful to tackle the problem of sending out emails but forgetting to include the relevant attachment (something that happens all too often). A common Information Retrieval (IR) approach in analyzing documents such as emails is to treat the entire document as a bag of words. Here we propose a finer-grained analysis to address the problem. We aim at identifying individual sentences within an email that refer to an attachment. If we detect any such sentence, we predict that the email should have an attachment. Using part of the Enron corpus for evaluation we find that our finer-grained approach outperforms previously reported document-level attachment prediction in similar evaluation settings.

  6. Attachment and Outcomes in Life

    Directory of Open Access Journals (Sweden)

    Neslim Guvendeger Doksat

    2016-12-01

    Full Text Available The term and ldquo;attachment and rdquo; is used to imply the bonding between mother and child or the relationship between parents and child. Establishment of secure attachment is the healthiest way for the mental and physical development of the child. Secure attachment system constitutes a protection mechanism from high levels of stress. Insecurely attached children are presented with mental and physical developmental delays and problems in identity formation and personality in the future. To avoid all these, all the requirements of the child by means of affection, nutrition, protection, shelter and health are required to be met in a consistent and healthy way by the caregiver. This review article discuss the term attachment; features associated with insecure attachment and its negative influences in adulthood. [Archives Medical Review Journal 2016; 25(4.000: 489-501

  7. The Nucleotide Capture Region of Alpha Hemolysin: Insights into Nanopore Design for DNA Sequencing from Molecular Dynamics Simulations

    Science.gov (United States)

    Manara, Richard M. A.; Tomasio, Susana; Khalid, Syma

    2015-01-01

    Nanopore technology for DNA sequencing is constantly being refined and improved. In strand sequencing a single strand of DNA is fed through a nanopore and subsequent fluctuations in the current are measured. A major hurdle is that the DNA is translocated through the pore at a rate that is too fast for the current measurement systems. An alternative approach is “exonuclease sequencing”, in which an exonuclease is attached to the nanopore that is able to process the strand, cleaving off one base at a time. The bases then flow through the nanopore and the current is measured. This method has the advantage of potentially solving the translocation rate problem, as the speed is controlled by the exonuclease. Here we consider the practical details of exonuclease attachment to the protein alpha hemolysin. We employ molecular dynamics simulations to determine the ideal (a) distance from alpha-hemolysin, and (b) the orientation of the monophosphate nucleotides upon release from the exonuclease such that they will enter the protein. Our results indicate an almost linear decrease in the probability of entry into the protein with increasing distance of nucleotide release. The nucleotide orientation is less significant for entry into the protein.

  8. The Nucleotide Capture Region of Alpha Hemolysin: Insights into Nanopore Design for DNA Sequencing from Molecular Dynamics Simulations.

    Science.gov (United States)

    Manara, Richard M A; Tomasio, Susana; Khalid, Syma

    2015-01-27

    Nanopore technology for DNA sequencing is constantly being refined and improved. In strand sequencing a single strand of DNA is fed through a nanopore and subsequent fluctuations in the current are measured. A major hurdle is that the DNA is translocated through the pore at a rate that is too fast for the current measurement systems. An alternative approach is "exonuclease sequencing", in which an exonuclease is attached to the nanopore that is able to process the strand, cleaving off one base at a time. The bases then flow through the nanopore and the current is measured. This method has the advantage of potentially solving the translocation rate problem, as the speed is controlled by the exonuclease. Here we consider the practical details of exonuclease attachment to the protein alpha hemolysin. We employ molecular dynamics simulations to determine the ideal (a) distance from alpha-hemolysin, and (b) the orientation of the monophosphate nucleotides upon release from the exonuclease such that they will enter the protein. Our results indicate an almost linear decrease in the probability of entry into the protein with increasing distance of nucleotide release. The nucleotide orientation is less significant for entry into the protein.

  9. Adult attachment and psychosocial functioning

    OpenAIRE

    Pielage, Suzanne Brenda

    2006-01-01

    In the trilogy Attachment, Separation and Loss (1969, 1973, 1980), Bowlby theorized that early experiences with caregivers affect the quality of individuals’ later (romantic) relationships and, consequently, their mental health. The current thesis set out to examine the relationships between adult attachment and psychosocial functioning, predominately in the realm of close relationships. In the first part of the thesis, the focus lay on the assessment of the adult attachment construct. In Cha...

  10. Synthetic Adhesive Attachment Discs based on Spider Pyriform Silk Architecture

    Science.gov (United States)

    Jain, Dharamdeep; Sahni, Vasav; Dhinojwala, Ali

    2014-03-01

    Among the variety of silks produced by spiders, pyriform silk is used in conjunction with the dragline silk to attach webs to different surfaces. Cob weaver spiders employ different architectural patterns to utilize the pyriform silk and form attachment joints with each pattern having a characteristic adhesive performance. The staple pin architecture is a one of the strongest attachment designs employed by spiders to attach their webs. Here we use a synthetic approach to create the a similar patterned architecture attachment discs on aluminum substrate using thermoplastic polyurethane. Measurable pull off forces are generated when the synthetic discs are peeled off a surface. This innovative adhesive strategy can be a source of design in various biomedical applications. Financial Support from National Science Foundation.

  11. Structure Based Drug Design for HIM Protease: From Molecular Modeling to Cheminformatics

    Energy Technology Data Exchange (ETDEWEB)

    Volarath, Patra; Weber, Irene T.; Harrison, Robert W. (GSU)

    2008-06-06

    Significant progress over the past decade in virtual representations of molecules and their physicochemical properties has produced new drugs from virtual screening of the structures of single protein molecules by conventional modeling methods. The development of clinical antiviral drugs from structural data for HIV protease has been a major success in structure based drug design. Techniques for virtual screening involve the ranking of the affinity of potential ligands for the target site on a protein. Two main alternatives have been developed: modeling of the target protein with a series of related ligand molecules, and docking molecules from a database to the target protein site. The computational speed and prediction accuracy will depend on the representation of the molecular structure and chemistry, the search or simulation algorithm, and the scoring function to rank the ligands. Moreover, the general challenges in modern computational drug design arise from the profusion of data, including whole genomes of DNA, protein structures, chemical libraries, affinity and pharmacological data. Therefore, software tools are being developed to manage and integrate diverse data, and extract and visualize meaningful relationships. Current areas of research include the development of searchable chemical databases, which requires new algorithms to represent molecules and search for structurally or chemically similar molecules, and the incorporation of machine learning techniques for data mining to improve the accuracy of predictions. Examples will be presented for the virtual screening of drugs that target HIV protease.

  12. Beyond Fullerenes: Designing Alternative Molecular Electron Acceptors for Solution-Processable Bulk Heterojunction Organic Photovoltaics.

    Science.gov (United States)

    Sauvé, Geneviève; Fernando, Roshan

    2015-09-17

    Organic photovoltaics (OPVs) are promising candidates for providing a low cost, widespread energy source by converting sunlight into electricity. Solution-processable active layers have predominantly consisted of a conjugated polymer donor blended with a fullerene derivative as the acceptor. Although fullerene derivatives have been the acceptor of choice, they have drawbacks such as weak visible light absorption and poor energy tuning that limit overall efficiencies. This has recently fueled new research to explore alternative acceptors that would overcome those limitations. During this exploration, one question arises: what are the important design principles for developing nonfullerene acceptors? It is generally accepted that acceptors should have high electron affinity, electron mobility, and absorption coefficient in the visible and near-IR region of the spectra. In this Perspective, we argue that alternative molecular acceptors, when blended with a conjugated polymer donor, should also have large nonplanar structures to promote nanoscale phase separation, charge separation and charge transport in blend films. Additionally, new material design should address the low dielectric constant of organic semiconductors that have so far limited their widespread application.

  13. Attachment disorganization in different clinical groups: What underpins unresolved attachment?

    Directory of Open Access Journals (Sweden)

    Juen Florian

    2013-01-01

    Full Text Available This paper summarizes findings and clinical implications of research on attachment disorganization in diverse clinical groups. Disorganized/unresolved attachment is overrepresented in these groups compared to healthy control participants, but disorder specific characteristics of this attachment pattern are still poorly understood. The focus of this study was to explore defensive processes in participants whose narratives were classified as disorganized/unresolved using the Adult Attachment Projective Picture System (AAP. Besides the predominance of disorganized attachment, clinical participants demonstrated more “segregated system material” especially in stories representing aloneness and more “Personal Experience material” compared to healthy individuals. Within the disorganized/ unresolved clinical individuals, BPD and PTSD patients showed the highest proportion of attachment disorganization and were less able to use other attachment-related defenses to maintain organized. Furthermore, PTSD patients were emotionally overwhelmed by the projective attachment scenes compared to the other clinical groups as indexed by an incapacity to complete sections of the AAP. BPD and addicted patients were characterized by a high degree of self-other boundary confusion. Depressive and schizophrenic patients showed a high overall defensive intensity to remain organized.

  14. Tetrapodal molecular switches and motors: synthesis and photochemistry.

    Science.gov (United States)

    Chen, Kuang-Yen; Wezenberg, Sander J; Carroll, Gregory T; London, Gábor; Kistemaker, Jos C M; Pijper, Thomas C; Feringa, Ben L

    2014-08-01

    The design, synthesis, and dynamic behavior of a series of novel tetrapodal molecular switches and motors containing common functional groups for attachment to various inorganic and organic surfaces are presented. Using a Diels-Alder reaction, an anthracene unit with four functionalized alkyl substituents ("legs") was coupled to maleimide-functionalized molecular switches or motors under ambient conditions. Terminal functional groups at the "legs" include thioacetates and azides, making these switches and motors ideal candidates for attachment to metallic or alkyne-functionalized surfaces. UV/vis absorption spectroscopy shows that the molecular switches and motors retain their ability to undergo reversible photoinduced and/or thermally induced structural changes after attachment to the tetrapodal anthracene.

  15. Protein Attachment on Nanodiamonds.

    Science.gov (United States)

    Lin, Chung-Lun; Lin, Cheng-Huang; Chang, Huan-Cheng; Su, Meng-Chih

    2015-07-16

    A recent advance in nanotechnology is the scale-up production of small and nonaggregated diamond nanoparticles suitable for biological applications. Using detonation nanodiamonds (NDs) with an average diameter of ∼4 nm as the adsorbents, we have studied the static attachment of three proteins (myoglobin, bovine serum albumin, and insulin) onto the nanoparticles by optical spectroscopy, mass spectrometry, and dynamic light scattering, and electrophoretic zeta potential measurements. Results show that the protein surface coverage is predominantly determined by the competition between protein-protein and protein-ND interactions, giving each protein a unique and characteristic structural configuration in its own complex. Specifically, both myoglobin and bovine serum albumin show a Langmuir-type adsorption behavior, forming 1:1 complexes at saturation, whereas insulin folds into a tightly bound multimer before adsorption. The markedly different adsorption patterns appear to be independent of the protein concentration and are closely related to the affinity of the individual proteins for the NDs. The present study provides a fundamental understanding for the use of NDs as a platform for nanomedical drug delivery.

  16. Substratum interfacial energetic effects on the attachment of marine bacteria

    Science.gov (United States)

    Ista, Linnea Kathryn

    Biofilms represent an ancient, ubiquitous and influential form of life on earth. Biofilm formation is initiated by attachment of bacterial cells from an aqueous suspension onto a suitable attachment substratum. While in certain, well studied cases initial attachment and subsequent biofilm formation is mediated by specific ligand-receptor pairs on the bacteria and attachment substratum, in the open environment, including the ocean, it is assumed to be non-specific and mediated by processes similar to those that drive adsorption of colloids at the water-solid interface. Colloidal principles are studied to determine the molecular and physicochemical interactions involved in the attachment of the model marine bacterium, Cobetia marina to model self-assembled monolayer surfaces. In the simplest application of colloidal principles the wettability of attachment substrata, as measured by the advancing contact angle of water (theta AW) on the surface, is frequently used as an approximation for the surface tension. We demonstrate the applicability of this approach for attachment of C. marina and algal zoospores and extend it to the development of a means to control attachment and release of microorganisms by altering and tuning surface thetaAW. In many cases, however, thetaAW does not capture all the information necessary to model attachment of bacteria to attachment substrata; SAMs with similar thetaAW attach different number of bacteria. More advanced colloidal models of initial bacterial attachment have evolved over the last several decades, with the emergence of the model proposed by van Oss, Chaudhury and Good (VCG) as preeminent. The VCG model enables calculation of interfacial tensions by dividing these into two major interactions thought to be important at biointerfaces: apolar, Lifshitz-van der Waals and polar, Lewis acid-base (including hydrogen bonding) interactions. These interfacial tensions are combined to yield DeltaGadh, the free energy associated with

  17. Modification to the Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Mexican Hat, Utah: Volume 1, Text, Attachments 1--6. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-01-01

    This document provides the modifications to the 1988 Remedial Action Plan (RAP) of the contaminated materials at the Monument Valley, Arizona, and Mexican Hat, Utah. The text detailing the modifications and attachments 1 through 6 are provided with this document. The RAP was developed to serve a two-fold purpose. It presents the activities proposed by the Department of Energy (DOE) to accomplish long-term stabilization and control of the residual radioactive materials (RRM) from Monument Valley, Arizona, and Mexican Hat, Utah, at the Mexican Hat disposal site. It also serves to document the concurrence of both the Navajo Nation and the Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE and the Navajo Nation and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement. This document has been structured to provide a comprehensive understanding of the remedial action proposed for the Monument Valley and Mexican Hat sites. It includes specific design and construction requirements for the remedial action. Pertinent information and data are included with reference given to the supporting documents.

  18. Attachment, caring and prosocial behavior

    NARCIS (Netherlands)

    Erez, Ayelet

    2007-01-01

    The thesis focuses on 5 studies examining the role of adult attachment in volunteering by defining volunteerism as a form of caregiving. By that we suggest an effect of one behavioral system, attachment, on another, caring or prosocial behaviors in individual or group settings. Studies 1 and 2 ex

  19. Collimator design for a dedicated molecular breast imaging-guided biopsy system: Proof-of-concept

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, Amanda L.; Hruska, Carrie B.; Conners, Amy L.; O' Connor, Michael K. [Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 (United States)

    2013-01-15

    Purpose: Molecular breast imaging (MBI) is a dedicated nuclear medicine breast imaging modality that employs dual-head cadmium zinc telluride (CZT) gamma cameras to functionally detect breast cancer. MBI has been shown to detect breast cancers otherwise occult on mammography and ultrasound. Currently, a MBI-guided biopsy system does not exist to biopsy such lesions. Our objective was to consider the utility of a novel conical slant-hole (CSH) collimator for rapid (<1 min) and accurate monitoring of lesion position to serve as part of a MBI-guided biopsy system. Methods: An initial CSH collimator design was derived from the dimensions of a parallel-hole collimator optimized for MBI performed with dual-head CZT gamma cameras. The parameters of the CSH collimator included the collimator height, cone slant angle, thickness of septa and cones of the collimator, and the annular areas exposed at the base of the cones. These parameters were varied within the geometric constraints of the MBI system to create several potential CSH collimator designs. The CSH collimator designs were evaluated using Monte Carlo simulations. The model included a breast compressed to a thickness of 6 cm with a 1-cm diameter lesion located 3 cm from the collimator face. The number of particles simulated was chosen to represent the count density of a low-dose, screening MBI study acquired with the parallel-hole collimator for 10 min after a {approx}150 MBq (4 mCi) injection of Tc-99m sestamibi. The same number of particles was used for the CSH collimator simulations. In the resulting simulated images, the count sensitivity, spatial resolution, and accuracy of the lesion depth determined from the lesion profile width were evaluated. Results: The CSH collimator design with default parameters derived from the optimal parallel-hole collimator provided 1-min images with error in the lesion depth estimation of 1.1 {+-} 0.7 mm and over 21 times the lesion count sensitivity relative to 1-min images

  20. Attachment styles in alcoholic inpatients.

    Science.gov (United States)

    De Rick, Ann; Vanheule, Stijn

    2007-01-01

    Despite the fact that addiction has often been identified as an attachment disorder, empirical studies on this topic are rather scarce. In our study we explore attachment style (secure vs. insecure) in alcoholic inpatients and its relationship with perceived parenting and alcohol-related and psychiatric problems in a sample of 101 alcoholic inpatients (Belgium). Our results reveal that in comparison to the securely-attached group, insecurely-attached alcoholic inpatients perceived their mother as more controlling, reported more severe psychiatric problems in the European Addiction Severity Index, had higher scores on the Beck Depression Inventory, showed more schizotypal and depressive personality traits and had more difficulties with communicating emotions (alexithymia). We argue that it makes sense to differentiate alcoholic inpatients on the basis of attachment style and that both groups (secure/insecure) need different treatment approaches.

  1. Designing and preparation of cytisine alkaloid surface-imprinted material and its molecular recognition characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Baojiao, E-mail: gaobaojiao@126.com [Department of Chemical Engineering, North University of China, Taiyuan 030051 (China); Bi, Concon [Department of Chemical Engineering, North University of China, Taiyuan 030051 (China); Fan, Li [School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China)

    2015-03-30

    Highlights: • An elaborate molecular design was well done for molecule surface-imprinting. • The new method of “pre-graft polymerizing and post-imprinting” was used. • Cytisine molecule surface-imprinted material was prepared. • Cytisine surface-imprinting depends on electrostatic interaction between host–guest. • The imprinted material has special recognition selectivity for template cytisine. - Abstract: Based on molecular design, a cytisine surface-imprinted material was prepared using the new surface-imprinting technique of “pre-graft polymerizing and post-imprinting”. The graft-polymerization of glycidyl methacrylate (GMA) on the surfaces of micron-sized silica gel particles was first performed with a surface-initiating system, preparing the grafted particles PGMA/SiO{sub 2}. Subsequently, a polymer reaction, the ring-opening reaction of the epoxy groups of the grafted PGMA, was conducted with sodium 2,4-diaminobenzene sulfonate (SAS) as reagent, resulting in the functional grafted particles SAS-PGMA/SiO{sub 2}. The adsorption of cytisine on SAS-PGMA/SiO{sub 2} particles reached saturation via strong electrostatic interaction between the sulfonate groups of SAS-PGMA/SiO{sub 2} particles and the protonated N atoms in cytisine molecule. Finally, cytisine surface-imprinting was successfully carried out with glutaraldehyde as crosslinker, obtaining cytisine surface-imprinted material MIP-SASP/SiO{sub 2}. The binding and recognition characteristics of MIP-SASP/SiO{sub 2} towards cytisine were investigated in depth. The experimental results show that there is strong electrostatic interaction between particles and cytisine molecules, and on this basis, cytisine surface-imprinting can be smoothly performed. The surface-imprinted MIP-SASP/SiO{sub 2} has special recognition selectivity and excellent binding affinity for cytisine, and the selectivity coefficients of MIP-SASP/SiO{sub 2} particles for cytisine relative to matrine and oxymatrine, which

  2. Estimation and Uncertainty Analysis of Flammability Properties for Computer-aided molecular design of working fluids for thermodynamic cycles

    OpenAIRE

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    2015-01-01

    Computer Aided Molecular Design (CAMD) is an important tool to generate, test and evaluate promising chemical products. CAMD can be used in thermodynamic cycle for the design of pure component or mixture working fluids in order to improve the heat transfer capacity of the system. The safety assessment of novel working fluids relies on accurate property data. Flammability data like the lower and upper flammability limit (LFL and UFL) play an important role in quantifying the risk of fire and e...

  3. Molecular design driving tetraporphyrin self-assembly on graphite: a joint STM, electrochemical and computational study

    Science.gov (United States)

    El Garah, M.; Santana Bonilla, A.; Ciesielski, A.; Gualandi, A.; Mengozzi, L.; Fiorani, A.; Iurlo, M.; Marcaccio, M.; Gutierrez, R.; Rapino, S.; Calvaresi, M.; Zerbetto, F.; Cuniberti, G.; Cozzi, P. G.; Paolucci, F.; Samorì, P.

    2016-07-01

    Tuning the intermolecular interactions among suitably designed molecules forming highly ordered self-assembled monolayers is a viable approach to control their organization at the supramolecular level. Such a tuning is particularly important when applied to sophisticated molecules combining functional units which possess specific electronic properties, such as electron/energy transfer, in order to develop multifunctional systems. Here we have synthesized two tetraferrocene-porphyrin derivatives that by design can selectively self-assemble at the graphite/liquid interface into either face-on or edge-on monolayer-thick architectures. The former supramolecular arrangement consists of two-dimensional planar networks based on hydrogen bonding among adjacent molecules whereas the latter relies on columnar assembly generated through intermolecular van der Waals interactions. Scanning Tunneling Microscopy (STM) at the solid-liquid interface has been corroborated by cyclic voltammetry measurements and assessed by theoretical calculations to gain multiscale insight into the arrangement of the molecule with respect to the basal plane of the surface. The STM analysis allowed the visualization of these assemblies with a sub-nanometer resolution, and cyclic voltammetry measurements provided direct evidence of the interactions of porphyrin and ferrocene with the graphite surface and offered also insight into the dynamics within the face-on and edge-on assemblies. The experimental findings were supported by theoretical calculations to shed light on the electronic and other physical properties of both assemblies. The capability to engineer the functional nanopatterns through self-assembly of porphyrins containing ferrocene units is a key step toward the bottom-up construction of multifunctional molecular nanostructures and nanodevices.Tuning the intermolecular interactions among suitably designed molecules forming highly ordered self-assembled monolayers is a viable approach to

  4. Design and Synthesis of a Highly Stable Six-hydrogen-bonded Self-assembly Yellowish Green Electroluminescent Molecular Duplex

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    This paper describes the design, synthesis and characterization of a hydrogen-bonded molecular duplex with 1,8-naphthalimide fluorescent pendants. The two oligoamide molecular strands, with complementary hydrogen bond sequences of DDADAA and AADADD, caa form an ultra stable self-assembly duplex. Its molecular structure was confirmed by 1H NMR and ESI-MS, and its photoluminescence properties were determined. The resulting duplex exhibited a dramatically enhanced photoluminescence (PL) quantum efficiency of 63.7% compared to the corresponding 1,8-naphthalimide segment (32.4%), suggesting that the formation of the duplex with larger molecular weight could successfully inhibit the quenching of the fluorescent pendant.This novel duplex is a prospective candidate for new electroluminescent emitter.

  5. Applying universal scaling laws to identify the best molecular design paradigms for second-order nonlinear optics

    CERN Document Server

    Perez-Moreno, Javier; Kuzyk, Mark G

    2016-01-01

    We apply scaling and the theory of the fundamental limits of the second-order molecular susceptibility to identify material classes with ultralarge nonlinear-optical response. Size effects are removed by normalizing all nonlinearities to get intrinsic values so that the scaling behavior of a series of molecular homologues can be determined. Several new figures of merit are proposed that quantify the desirable properties for molecules that can be designed by adding a sequence of repeat units, and used in the assessment of the data. Three molecular classes are found. They are characterized by sub-scaling, nominal scaling, or super-scaling. Super-scaling homologues most efficiently take advantage of increased size. We apply our approach to data currently available in the literature to identify the best super-scaling molecular paradigms with the aim of identifying desirable traits of new materials.

  6. Differential scanning calorimetry in life science: thermodynamics, stability, molecular recognition and application in drug design.

    Science.gov (United States)

    Bruylants, G; Wouters, J; Michaux, C

    2005-01-01

    All biological phenomena depend on molecular recognition, which is either intermolecular like in ligand binding to a macromolecule or intramolecular like in protein folding. As a result, understanding the relationship between the structure of proteins and the energetics of their stability and binding with others (bio)molecules is a very interesting point in biochemistry and biotechnology. It is essential to the engineering of stable proteins and to the structure-based design of pharmaceutical ligands. The parameter generally used to characterize the stability of a system (the folded and unfolded state of the protein for example) is the equilibrium constant (K) or the free energy (deltaG(o)), which is the sum of enthalpic (deltaH(o)) and entropic (deltaS(o)) terms. These parameters are temperature dependent through the heat capacity change (deltaCp). The thermodynamic parameters deltaH(o) and deltaCp can be derived from spectroscopic experiments, using the van't Hoff method, or measured directly using calorimetry. Along with isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) is a powerful method, less described than ITC, for measuring directly the thermodynamic parameters which characterize biomolecules. In this article, we summarize the principal thermodynamics parameters, describe the DSC approach and review some systems to which it has been applied. DSC is much used for the study of the stability and the folding of biomolecules, but it can also be applied in order to understand biomolecular interactions and can thus be an interesting technique in the process of drug design.

  7. Design, Development and Implementation of a Technology Enhanced Hybrid Course on Molecular Symmetry: Students' Outcomes and Attitudes

    Science.gov (United States)

    Antonoglou, L. D.; Charistos, N. D.; Sigalas, M. P.

    2011-01-01

    A hybrid course of Molecular Symmetry and Group Theory which combines traditional face-to-face instruction with an online web enhanced learning environment within a Course Management System was designed, developed, and implemented with a purpose to establish an active and student-centred educational setting. Multi-representational educational…

  8. The Impact of Designing and Evaluating Molecular Animations on How Well Middle School Students Understand the Particulate Nature of Matter

    Science.gov (United States)

    Chang, Hsin-Yi; Quintana, Chris; Krajcik, Joseph S.

    2010-01-01

    In this study, we investigated whether the understanding of the particulate nature of matter by students was improved by allowing them to design and evaluate molecular animations of chemical phenomena. We developed Chemation, a learner-centered animation tool, to allow seventh-grade students to construct flipbook-like simple animations to show…

  9. Towards the design of new and improved drilling fluid additives using molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Richard L. Anderson

    2010-03-01

    Full Text Available During exploration for oil and gas, a technical drilling fluid is used to lubricate the drill bit, maintain hydrostatic pressure, transmit sensor readings, remove rock cuttings and inhibit swelling of unstable clay based reactive shale formations. Increasing environmental awareness and resulting legislation has led to the search for new, improved biodegradable drilling fluid components. In the case of additives for clay swelling inhibition, an understanding of how existing effective additives interact with clays must be gained to allow the design of improved molecules. Owing to the disordered nature and nanoscopic dimension of the interlayer pores of clay minerals, computer simulations have become an increasingly useful tool for studying clay-swelling inhibitor interactions. In this work we briefly review the history of the development of technical drilling fluids, the environmental impact of drilling fluids and the use of computer simulations to study the interactions between clay minerals and swelling inhibitors. We report on results from some recent large-scale molecular dynamics simulation studies on low molecular weight water-soluble macromolecular inhibitor molecules. The structure and interactions of poly(propylene oxide-diamine, poly(ethylene glycol and poly(ethylene oxide-diacrylate inhibitor molecules with montmorillonite clay are studied.Durante a exploração de óleo e gás um fluido de perfuração é usado para lubrificar 'bit' da perfuradora, manter a pressão hidrostática, transmitir sensores de leitura, remover resíduos da rocha e inibir o inchamento da argila instável baseada nas formações dos folhelhos. O aumento das preocupações ambientais bem como a legislação resultante levou à procura de novos fluidos de perfuração com componentes biodegradáveis. No caso dos aditivos para inibir o inchamento das argilas o entendimento das interações entre os aditivos e as argilas tem que ser adquirido para permitir o

  10. Molecular Electrical Doping of Organic Semiconductors: Fundamental Mechanisms and Emerging Dopant Design Rules.

    Science.gov (United States)

    Salzmann, Ingo; Heimel, Georg; Oehzelt, Martin; Winkler, Stefanie; Koch, Norbert

    2016-03-15

    Today's information society depends on our ability to controllably dope inorganic semiconductors, such as silicon, thereby tuning their electrical properties to application-specific demands. For optoelectronic devices, organic semiconductors, that is, conjugated polymers and molecules, have emerged as superior alternative owing to the ease of tuning their optical gap through chemical variability and their potential for low-cost, large-area processing on flexible substrates. There, the potential of molecular electrical doping for improving the performance of, for example, organic light-emitting devices or organic solar cells has only recently been established. The doping efficiency, however, remains conspicuously low, highlighting the fact that the underlying mechanisms of molecular doping in organic semiconductors are only little understood compared with their inorganic counterparts. Here, we review the broad range of phenomena observed upon molecularly doping organic semiconductors and identify two distinctly different scenarios: the pairwise formation of both organic semiconductor and dopant ions on one hand and the emergence of ground state charge transfer complexes between organic semiconductor and dopant through supramolecular hybridization of their respective frontier molecular orbitals on the other hand. Evidence for the occurrence of these two scenarios is subsequently discussed on the basis of the characteristic and strikingly different signatures of the individual species involved in the respective doping processes in a variety of spectroscopic techniques. The critical importance of a statistical view of doping, rather than a bimolecular picture, is then highlighted by employing numerical simulations, which reveal one of the main differences between inorganic and organic semiconductors to be their respective density of electronic states and the doping induced changes thereof. Engineering the density of states of doped organic semiconductors, the Fermi

  11. Transfer of attachment functions and adjustment among young adults in China.

    Science.gov (United States)

    Zhang, Hong; Chan, Darius K-S; Teng, Fei

    2011-01-01

    This study was designed to examine the process of attachment transfer from parents to peers, as well as factors related to this transfer process among Mainland Chinese. A total of 147 Chinese college students (with a mean age of 21.44) completed questionnaires that measured attachment style, attachment transfer, attachment support from various figures, loneliness, positive/negative affects, and self-esteem. Major findings of the current study include the following: (a) Hazan and Shaver's sequential model of attachment transfer was generalized to the Chinese sample; (b) the extent of attachment transfer was found to be associated with participants' emotional states (loneliness and positive affect) and was a significant predictor of these emotional states beyond the effects of attachment style and attachment support. As one of the first studies exploring the phenomenon of attachment transfer among young Chinese adults, conceptual and applied implications of these findings are discussed.

  12. Guidance to Design Grain Boundary Mobility Experiments with Molecular Dynamics and Phase-Field Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Michael R Tonks; Yongfeng Zhang; S.B. Biner; Paul C Millett; Xianming Bai

    2013-02-01

    Quantitative phase-field modeling can play an important role in designing experiments to measure the grain boundary (GB) mobility. In this work, molecular dynamics (MD) simulation is employed to determine the GB mobility using Cu bicrystals. Two grain configurations are considered: a shrinking circular grain and a half loop grain. The results obtained from the half loop configuration approaches asymptotically to that obtained from the circular configuration with increasing half loop width. We then verify the phase- field model by directly comparing to the MD simulation results, obtaining excellent agreement. Next, this phase-field model is used to predict the behavior in a common experimental setup that utilizes a half loop grain configuration in a bicrystal to measure the GB mobility. With a 3D simulation, we identify the two critical times within the experiments to reach an accurate value of the GB mobility. We use a series of 2D simulations to investigate the impact of the notch angle on these two critical times and we identify an angle of 60? as an optimal value. We also show that if the notch does not have a sharp tip, it may immobilize the GB migration indefinitely.

  13. Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation.

    Science.gov (United States)

    Wu, Ming-Yu; Esteban, Gerard; Brogi, Simone; Shionoya, Masahi; Wang, Li; Campiani, Giuseppe; Unzeta, Mercedes; Inokuchi, Tsutomu; Butini, Stefania; Marco-Contelles, Jose

    2016-10-01

    Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the disease symptoms resulting in a moderate improvement in memory and cognitive function without any efficacy in preventing and inhibiting the progression of the pathology. In an effort to obtain disease-modifying anti-Alzheimer's drugs (DMAADs) following the multifactorial nature of AD, we have recently developed multifunctional compounds. We herein describe the design, synthesis, molecular modeling and biological evaluation of a new series of donepezil-related compounds possessing metal chelating properties, and being capable of targeting different enzymatic systems related to AD (cholinesterases, ChEs, and monoamine oxidase A, MAO-A). Among this set of analogues compound 5f showed excellent ChEs inhibition potency and a selective MAO-A inhibition (vs MAO-B) coupled to strong complexing properties for zinc and copper ions, both known to be involved in the progression of AD. Moreover, 5f exhibited moderate antioxidant properties as found by in vitro assessment. This compound represents a novel donepezil-hydroxyquinoline hybrid with DMAAD profile paving the way to the development of a novel class of drugs potentially able to treat AD.

  14. ADVANCED MOLECULAR DESIGN OF BIOPOLYMERS FOR TRANSMUCOSAL AND INTRACELLULAR DELIVERY OF CHEMOTHERAPEUTIC AGENTS AND BIOLOGICAL THERAPEUTICS

    Science.gov (United States)

    Liechty, William B.; Caldorera-Moore, Mary; Phillips, Margaret A.; Schoener, Cody; Peppas, Nicholas A.

    2011-01-01

    Hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli. In this contribution, we outline a multifaceted hydrogel-based approach for expanding the range of therapeutics in oral formulations from classical small-molecule drugs to include proteins, chemotherapeutics, and nucleic acids. Through judicious materials selection and careful design of copolymer composition and molecular architecture, we can engineer systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action. These hydrogel carriers, including complexation hydrogels, tethered hydrogels, interpenetrating networks, nanoscale hydrogels, and hydrogels with decorated structures are investigated for their ability respond to changes in pH, to load and release insulin and fluorescein, and remain non-toxic to Caco-2 cells. Our results suggest these novel hydrogel networks have great potential for controlled delivery of proteins, chemotherapeutics, and nucleic acids. PMID:21699934

  15. A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents

    Institute of Scientific and Technical Information of China (English)

    CHEN JinCan; QIAN Li; SHEN Yong; CHEN LanMei; ZHENG KangCheng

    2008-01-01

    A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis.A new scheme deter-mining outliers by "leave-one-out" (LOO) cross-validation coefficient (q2n-1) was suggested and suc-cessfully used.In the established optimal equation (excluding two outliers), the steric parameter (MRR) and the net charge (QFR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (IgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds.The fitting correlation coefficient (R2) and the cross-validation coefficient (q2) values are 0.883 and 0.797, respectively.It indicates that this model has a significantly statistical quality and an excellent prediction ability.Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.

  16. A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis. A new scheme determining outliers by "leave-one-out" (LOO) cross-validation coefficient (q2n-i) was suggested and successfully used. In the established optimal equation (excluding two outliers), the steric parameter (MRR) and the net charge (QFR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (lgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds. The fitting correlation coefficient (R2) and the cross-validation coefficient (q2) values are 0.883 and 0.797, respectively. It indicates that this model has a significantly statistical quality and an excellent prediction ability. Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.

  17. Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics.

    Science.gov (United States)

    Lau, Wan F; Withka, Jane M; Hepworth, David; Magee, Thomas V; Du, Yuhua J; Bakken, Gregory A; Miller, Michael D; Hendsch, Zachary S; Thanabal, Venkataraman; Kolodziej, Steve A; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S; Love, Robert; Charlton, Maura E; Hughes, Samantha; van Hoorn, Willem P; Mills, James E

    2011-07-01

    Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

  18. Molecular Design of Bioinspired Nanostructures for Biomedical Applications: Synthesis, Self-Assembly and Functional Properties

    Science.gov (United States)

    Xu, Hesheng Victor; Zheng, Xin Ting; Mok, Beverly Yin Leng; Ibrahim, Salwa Ali; Yu, Yong; Tan, Yen Nee

    2016-08-01

    Biomolecules are the nanoscale building blocks of cells, which play multifaceted roles in the critical biological processes such as biomineralization in a living organism. In these processes, the biological molecules such as protein and nucleic acids use their exclusive biorecognition properties enabled from their unique chemical composition, shape and function to initiate a cascade of cellular events. The exceptional features of these biomolecules, coupled with the recent advancement in nanotechnology, have led to the emergence of a new research field that focuses on the molecular design of bioinspired nanostructures that inherit the extraordinary function of natural biomaterials. These “bioinspired” nanostructures could be formulated by biomimetic approaches through either self-assembling of biomolecules or acting as a biomolecular template/precursor to direct the synthesis of nanocomposite. In either situation, the resulting nanomaterials exhibit phenomenal biocompatibility, superb aqueous solubility and excellent colloidal stability, branding them exceptionally desirable for both in vitro and in vivo biomedical applications. In this review, we will present the recent developments in the preparation of “bioinspired” nanostructures through biomimetic self-assembly and biotemplating synthesis, as well as highlight their functional properties and potential applications in biomedical diagnostics and therapeutic delivery. Lastly, we will conclude this topic with some personal perspective on the challenges and future outlooks of the “bioinspired” nanostructures for nanomedicine.

  19. Discovery and design of cyclic peptides as dengue virus inhibitors through structure-based molecular docking

    Institute of Scientific and Technical Information of China (English)

    Sobia Idrees; Usman Ali Ashfaq

    2014-01-01

    Objective:To find potential peptide inhibitors against theNS2B/NS3 protease ofDENV which in turn, can inhibit the viral replication inside host cell.Methods:Cyclic peptides were designed having combination of positively charged amino acids usingChemSketch software and were converted to3D structures.DENVNS3 protein structure was retrieved fromProteinDataBank (PDB) usingPDBId:2FOM.DENVNS3 and cylic peptides were docked usingMOE software after structural optimization.Results:Through molecular docking it was revealed that most of the peptides bound deeply in the binding pocket ofDENVNS2B/NS3 protease an had interactions with catalytic triad.Peptide2 successfully blocked the catalytic triad ofNS2B/NS3 protease. Peptide1, ,4 and6 also had potential interactions with active residues of theNS2B/NS3 protease while all other peptides were in close contact with the active sites ofNS2B/NS3 protease thus, these peptides can serve as a potential drug candidate to stop viral replication.Conclusions:Thus, it can be concluded from the study that these peptides could serve as important inhibitors to inhibit the viral replication and need further in-vitro investigations to confirm their efficacy.

  20. Molecular Design of Ionization-Induced Proton Switching Element Based on Fluorinated DNA Base Pair.

    Science.gov (United States)

    Tachikawa, Hiroto; Kawabata, Hiroshi

    2016-03-10

    To design theoretically the high-performance proton switching element based on DNA base pair, the effects of fluorine substitution on the rate of proton transfer (PT) in the DNA model base pair have been investigated by means of direct ab initio molecular dynamics (AIMD) method. The 2-aminopyridine dimer, (AP)2, was used as the model of the DNA base pair. One of the hydrogen atoms of the AP molecule in the dimer was substituted by a fluorine (F) atom, and the structures of the dimer, expressed by F-(AP)2, were fully optimized at the MP2/6-311++G(d,p) level. The direct AIMD calculations showed that the proton is transferred within the base pair after the vertical ionization. The rates of PT in F-(AP)2(+) were calculated and compared with that of (AP)2(+) without an F atom. It was found that PT rate is accelerated by the F-substitution. Also, the direction of PT between F-AP and AP molecules can be clearly controlled by the position of F-substitution (AP)2 in the dimer.

  1. RNAiFold: a web server for RNA inverse folding and molecular design.

    Science.gov (United States)

    Garcia-Martin, Juan Antonio; Clote, Peter; Dotu, Ivan

    2013-07-01

    Synthetic biology and nanotechnology are poised to make revolutionary contributions to the 21st century. In this article, we describe a new web server to support in silico RNA molecular design. Given an input target RNA secondary structure, together with optional constraints, such as requiring GC-content to lie within a certain range, requiring the number of strong (GC), weak (AU) and wobble (GU) base pairs to lie in a certain range, the RNAiFold web server determines one or more RNA sequences, whose minimum free-energy secondary structure is the target structure. RNAiFold provides access to two servers: RNA-CPdesign, which applies constraint programming, and RNA-LNSdesign, which applies the large neighborhood search heuristic; hence, it is suitable for larger input structures. Both servers can also solve the RNA inverse hybridization problem, i.e. given a representation of the desired hybridization structure, RNAiFold returns two sequences, whose minimum free-energy hybridization is the input target structure. The web server is publicly accessible at http://bioinformatics.bc.edu/clotelab/RNAiFold, which provides access to two specialized servers: RNA-CPdesign and RNA-LNSdesign. Source code for the underlying algorithms, implemented in COMET and supported on linux, can be downloaded at the server website.

  2. Designing metal hydride complexes for water splitting reactions: a molecular electrostatic potential approach.

    Science.gov (United States)

    Sandhya, K S; Suresh, Cherumuttathu H

    2014-08-28

    The hydridic character of octahedral metal hydride complexes of groups VI, VII and VIII has been systematically studied using molecular electrostatic potential (MESP) topography. The absolute minimum of MESP at the hydride ligand (Vmin) and the MESP value at the hydride nucleus (VH) are found to be very good measures of the hydridic character of the hydride ligand. The increasing/decreasing electron donating feature of the ligand environment is clearly reflected in the increasing/decreasing negative character of Vmin and VH. The formation of an outer sphere metal hydride-water complex showing the HH dihydrogen interaction is supported by the location and the value of Vmin near the hydride ligand. A higher negative MESP suggested lower activation energy for H2 elimination. Thus, MESP features provided a way to fine-tune the ligand environment of a metal-hydride complex to achieve high hydridicity for the hydride ligand. The applicability of an MESP based hydridic descriptor in designing water splitting reactions is tested for group VI metal hydride model complexes of tungsten.

  3. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano

    2012-02-01

    Full Text Available Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma, mechanisms of intercellular transference of genetic information (exosomes, and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.

  4. Co-encapsulating nanostructured lipid carriers for transdermal application: from experimental design to the molecular detail.

    Science.gov (United States)

    Vitorino, C; Almeida, J; Gonçalves, L M; Almeida, A J; Sousa, J J; Pais, A A C C

    2013-05-10

    Co-encapsulation of drugs directed at commonly associated diseases provides a convenient means for administration, especially if transdermally delivered. In this work, a comprehensive study for the co-encapsulation of drugs with a differential lipophilicity, olanzapine and simvastatin, and their transdermal delivery in a formulation containing nanostructured lipid carriers (NLC) is presented. Focus is given to the evaluation of a strategy in which NLC and chemical permeation enhancers are combined. It comprises in vitro, in silico and cellular viability approaches. The optimization and rationalization of the systems are carried out using a two-step factorial design. It is shown that the external medium in the NLC dispersion strongly influences permeation. It is also seen that the use of NLC determines a synergistic effect with selected permeation enhancers, thus promoting marked flux enhancement ratios (48 and 21, respectively for olanzapine and simvastatin) relative to the drugs in solution. The developed formulations can be considered non-irritant. A correlation between enhancer positioning in a lipid bilayer, partially governed by a H-bonding phenomenon, and enhancement effect is suggested from molecular dynamics studies and experimental observations.

  5. Attachment relationships and physical activity motivation of college students.

    Science.gov (United States)

    Ullrich-French, Sarah; Smith, Alan L; Cox, Anne E

    2011-08-01

    This study was designed to assess the link of attachment relationships with physical activity motivation. Potential mediators of this link were examined in a cross-sectional study targeting college student physical activity motivation and behaviour. Participants completed self-reports of attachment relationships (with mother, father and best friend), self-determined motivation for physical activity, physical activity behaviour and the hypothesised mediator variables of perceived competence, autonomy and relatedness. The results provide support for the mediating role of these variables in the association of father attachment with self-determined motivation. Meaningful variance in self-determined motivation for physical activity and physical activity behaviour was explained. Overall, attachment relationships appear to be relevant, albeit modestly, to physical activity motivation of college students. The findings support continued efforts to integrate attachment and motivational perspectives in the study of college student health behaviour.

  6. A simple DNA handle attachment method for single molecule mechanical manipulation experiments.

    Science.gov (United States)

    Min, Duyoung; Arbing, Mark A; Jefferson, Robert E; Bowie, James U

    2016-08-01

    Manipulating single molecules and systems of molecules with mechanical force is a powerful technique to examine their physical properties. Applying force requires attachment of the target molecule to larger objects using some sort of molecular tether, such as a strand of DNA. DNA handle attachment often requires difficult manipulations of the target molecule, which can preclude attachment to unstable, hard to obtain, and/or large, complex targets. Here we describe a method for covalent DNA handle attachment to proteins that simply requires the addition of a preprepared reagent to the protein and a short incubation. The handle attachment method developed here provides a facile approach for studying the biomechanics of biological systems.

  7. Development of a model for the rational design of molecular imprinted polymer: Computational approach for combined molecular dynamics/quantum mechanics calculations

    Energy Technology Data Exchange (ETDEWEB)

    Dong Cunku [Department of Chemistry, Harbin Institute of Technology, Harbin 150090 (China); Li Xin, E-mail: lixin@hit.edu.cn [Department of Chemistry, Harbin Institute of Technology, Harbin 150090 (China); Guo Zechong [School of Municipal Environmental Engineering, Harbin Institute of Technology, Harbin 150090 (China); Qi Jingyao, E-mail: jyq@hit.edu.cn [School of Municipal Environmental Engineering, Harbin Institute of Technology, Harbin 150090 (China)

    2009-08-04

    A new rational approach for the preparation of molecularly imprinted polymer (MIP) based on the combination of molecular dynamics (MD) simulations and quantum mechanics (QM) calculations is described in this work. Before performing molecular modeling, a virtual library of functional monomers was created containing forty frequently used monomers. The MD simulations were first conducted to screen the top three monomers from virtual library in each porogen-acetonitrile, chloroform and carbon tetrachloride. QM simulations were then performed with an aim to select the optimum monomer and progen solvent in which the QM simulations were carried out; the monomers giving the highest binding energies were chosen as the candidate to prepare MIP in its corresponding solvent. The acetochlor, a widely used herbicide, was chosen as the target analyte. According to the theoretical calculation results, the MIP with acetochlor as template was prepared by emulsion polymerization method using N,N-methylene bisacrylamide (MBAAM) as functional monomer and divinylbenzene (DVB) as cross-linker in chloroform. The synthesized MIP was then tested by equilibrium-adsorption method, and the MIP demonstrated high removal efficiency to the acetochlor. Mulliken charge distribution and {sup 1}H NMR spectroscopy of the synthesized MIP provided insight on the nature of recognition during the imprinting process probing the governing interactions for selective binding site formation at a molecular level. We think the computer simulation method first proposed in this paper is a novel and reliable method for the design and synthesis of MIP.

  8. Everything You Want To Know about Attachment.

    Science.gov (United States)

    Honig, Alice Sterling

    This paper discusses infant attachment, which it defines as a long-lasting emotional bond revealed when a child under stress seeks out and tries to stay close to a specific figure. The paper addresses: (1) What is attachment? Who are the pioneers in attachment theory?; (2) How do we notice attachment in action?; (3) Is attachment the only…

  9. Direction-specific interactions control crystal growth by oriented attachment

    DEFF Research Database (Denmark)

    Li, Dongsheng; Nielsen, Michael H; Lee, Jonathan R.I.;

    2012-01-01

    The oriented attachment of molecular clusters and nanoparticles in solution is now recognized as an important mechanism of crystal growth in many materials, yet the alignment process and attachment mechanism have not been established. We performed high-resolution transmission electron microscopy...... using a fluid cell to directly observe oriented attachment of iron oxyhydroxide nanoparticles. The particles undergo continuous rotation and interaction until they find a perfect lattice match. A sudden jump to contact then occurs over less than 1 nanometer, followed by lateral atom-by-atom addition...... initiated at the contact point. Interface elimination proceeds at a rate consistent with the curvature dependence of the Gibbs free energy. Measured translational and rotational accelerations show that strong, highly direction-specific interactions drive crystal growth via oriented attachment....

  10. Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

    Science.gov (United States)

    Shah, Dhiral Ashwin

    Intracellular delivery of specific proteins and peptides represents a novel method to influence stem cells for gain-of-function and loss-of-function. Signaling control is vital in stem cells, wherein intricate control of and interplay among critical pathways directs the fate of these cells into either self-renewal or differentiation. The most common route to manipulate cellular function involves the introduction of genetic material such as full-length genes and shRNA into the cell to generate (or prevent formation of) the target protein, and thereby ultimately alter cell function. However, viral-mediated gene delivery may result in relatively slow expression of proteins and prevalence of oncogene insertion into the cell, which can alter cell function in an unpredictable fashion, and non-viral delivery may lead to low efficiency of genetic delivery. For example, the latter case plagues the generation of induced pluripotent stem cells (iPSCs) and hinders their use for in vivo applications. Alternatively, introducing proteins into cells that specifically recognize and influence target proteins, can result in immediate deactivation or activation of key signaling pathways within the cell. In this work, we demonstrate the cellular delivery of functional proteins attached to hydrophobically modified silica (SiNP) nanoparticles to manipulate specifically targeted cell signaling proteins. In the Wnt signaling pathway, we have targeted the phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta) by designing a chimeric protein and delivering it in neural stem cells. Confocal imaging indicates that the SiNP-chimeric protein conjugates were efficiently delivered to the cytosol of human embryonic kidney cells and rat neural stem cells, presumably via endocytosis. This uptake impacted the Wnt signaling cascade, indicated by the elevation of beta-catenin levels, and increased transcription of Wnt target genes, such as c-MYC. The results presented here suggest that

  11. Global sensitivity analysis of computer-aided molecular design problem for the development of novel working fluids for power cycles

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    2016-01-01

    study involving the design of a working fluid for an Organic Ranking Cycle (ORC) design for power generation. Morris Screening is found to be favorable over Monte Carlo based standard regression. Monte Carlo based standard regression cannot be applied, because the current model cannot be sufficiently......This study compares two methods for global sensitivity analysis as a new approach for the identification and ranking of target properties in molecular design problems: A modified Morris Screening technique and Monte Carlo based standard regression. The two methodologies are highlighted in a case...

  12. Attachment of Sulfolobus acidocaldarius cells on coal particles

    Energy Technology Data Exchange (ETDEWEB)

    Chiu-Yu Chen; Skidmore, D.R.

    1988-03-01

    Attachment of the thermophilic microorganism Sulfolobus acidocaldarius was studied on Kentucky No. 9 coal, an Ohio coal mixtures, Ohio No. 6, a European coal designated as Sulzer coal, activated carbon and iron pyrite to define the effects of initial cell density, prior acid leaching, pyrite content, and surface area on rate and extent of preleaching attachment. The results showed that the rate of preleaching attachment was so high that equilibrium was reached in less than 5 min in most cases. Attached cells increased in number with increasing initial cell density. Prior nitric acid leaching of coal reduced the extent of cell adsorption while hydrochloric acid leaching did not affect cell attachment. Some adsorption isotherms fit the Langmuir model. The specific adsorption (cells/cm/sup 3/ coal) increased with increasing surface areas measured by nitrogen adsorption. Pyrite gave the highest extent of cell attachment based on per unit surface area comparison. Adsorption isotherms of a pyrite-selective chemical adsorbate revealed that preleaching attachment of cells was affected further by altered surface properties of the coals and that the concept of selective attachment of cells on pyrite surfaces was also supported. 22 refs., 6 figs., 1 tab.

  13. Computational design of molecular tweezers and cranes with enhanced ion-pi interactions

    OpenAIRE

    Sanchez Lozano, Marta

    2014-01-01

    El objetivo principal de esta tesis ha sido diseño computacional de pinzas y grúas moleculares. Las pinzas y grúas moleculares son motores a escala molecular que permiten el ensamblaje de estructuras complejas, como circuitos eléctricos, manipulando moléculas individuales de forma ordenada. En esta tesis se llevó a cabo el diseño de nuevas pinzas y grúas moleculares con una gran especificidad hacia el sustrato y que posean un mecanismo sencillo de control externo de su operatividad. Un aspect...

  14. Attachment at work and performance.

    Science.gov (United States)

    Neustadt, Elizabeth A; Chamorro-Premuzic, Tomas; Furnham, Adrian

    2011-09-01

    This paper examines the relations between self-reported attachment orientation at work and personality, self-esteem, trait emotional intelligence (aka emotional self-efficacy), and independently assessed career potential and job performance. Self-report data were collected from 211 managers in an international business in the hospitality industry; independent assessments of these managers' job performance and career potential were separately obtained from the organization. A self-report measure of romantic attachment was adapted for application in the work context; a two-factor solution was found for this measure. Secure/autonomous attachment orientation at work was positively related to self-esteem, trait emotional intelligence, extraversion, agreeableness, and conscientiousness, and also to job performance. Not only was secure/autonomous attachment orientation at work statistically predictive of job performance, but the new measure also made a distinct contribution, beyond conscientiousness, to this prediction.

  15. Mapping and measuring place attachment

    DEFF Research Database (Denmark)

    Brown, Greg; Raymond, Christopher Mark; Corcoran, Jonathan

    2015-01-01

    in a regional study in South Australia. Our research objectives were to (1) analyze and present the spatial results of the mapping method as a benchmark for future research, (2) compare mapped place attachment to the more common practice of mapping landscape values in PPGIS that comprise a values home range, (3......-based measures. The area of place attachment is influenced by occupational roles such as farming or conservation, as well as home location, especially in coastal versus non-coastal contexts. The spatial distribution of mapped landscape values or values home range is related to, but not identical to mapped place......The concept of place attachment has been studied extensively across multiple disciplines but only recently with empirical measurement using public participation GIS (PPGIS) and related crowd-sourcing mapping methods. This research trialed a spatially explicit method for identifying place attachment...

  16. Attachment Narratives in Refugee Children

    DEFF Research Database (Denmark)

    De Haene, L.; Dalgård, Nina Thorup; Montgomery, E.

    2013-01-01

    J Trauma Stress. 2013 Jun;26(3):413-7. doi: 10.1002/jts.21820. Attachment narratives in refugee children: interrater reliability and qualitative analysis in pilot findings from a two-site study.......J Trauma Stress. 2013 Jun;26(3):413-7. doi: 10.1002/jts.21820. Attachment narratives in refugee children: interrater reliability and qualitative analysis in pilot findings from a two-site study....

  17. Hydration Free Energy as a Molecular Descriptor in Drug Design: A Feasibility Study.

    Science.gov (United States)

    Zafar, Ayesha; Reynisson, Jóhannes

    2016-05-01

    In this work the idea was investigated whether calculated hydration energy (ΔGhyd ) can be used as a molecular descriptor in defining promising regions of chemical space for drug design. Calculating ΔGhyd using the Density Solvation Model (SMD) in conjunction with the density functional theory (DFT) gave an excellent correlation with experimental values. Furthermore, calculated ΔGhyd correlates reasonably well with experimental water solubility (r(2) =0.545) and also log P (r(2) =0.530). Three compound collections were used: Known drugs (n=150), drug-like compounds (n=100) and simple organic compounds (n=140). As an approximation only molecules, which do not de/protonate at physiological pH were considered. A relatively broad distribution was seen for the known drugs with an average at -15.3 kcal/mol and a standard deviation of 7.5 kcal/mol. Interestingly, much lower averages were found for the drug-like compounds (-7.5 kcal/mol) and the simple organic compounds (-3.1 kcal/mol) with tighter distributions; 4.3 and 3.2 kcal/mol, respectively. This trend was not observed for these collections when calculated log P and log S values were used. The considerable greater exothermic ΔGhyd average for the known drugs clearly indicates in order to develop a successful drug candidate value of ΔGhyd <-5 kcal/mol or less is preferable.

  18. Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives.

    Science.gov (United States)

    Song, Zi-Long; Wang, Mei-Juan; Li, Lanlan; Wu, Dan; Wang, Yu-Han; Yan, Li-Ting; Morris-Natschke, Susan L; Liu, Ying-Qian; Zhao, Yong-Long; Wang, Chih-Ya; Liu, Huanxiang; Goto, Masuo; Liu, Heng; Zhu, Gao-Xiang; Lee, Kuo-Hsiung

    2016-06-10

    In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure-activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π-π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.

  19. Designing and preparation of cytisine alkaloid surface-imprinted material and its molecular recognition characteristics

    Science.gov (United States)

    Gao, Baojiao; Bi, Concon; Fan, Li

    2015-03-01

    Based on molecular design, a cytisine surface-imprinted material was prepared using the new surface-imprinting technique of "pre-graft polymerizing and post-imprinting". The graft-polymerization of glycidyl methacrylate (GMA) on the surfaces of micron-sized silica gel particles was first performed with a surface-initiating system, preparing the grafted particles PGMA/SiO2. Subsequently, a polymer reaction, the ring-opening reaction of the epoxy groups of the grafted PGMA, was conducted with sodium 2,4-diaminobenzene sulfonate (SAS) as reagent, resulting in the functional grafted particles SAS-PGMA/SiO2. The adsorption of cytisine on SAS-PGMA/SiO2 particles reached saturation via strong electrostatic interaction between the sulfonate groups of SAS-PGMA/SiO2 particles and the protonated N atoms in cytisine molecule. Finally, cytisine surface-imprinting was successfully carried out with glutaraldehyde as crosslinker, obtaining cytisine surface-imprinted material MIP-SASP/SiO2. The binding and recognition characteristics of MIP-SASP/SiO2 towards cytisine were investigated in depth. The experimental results show that there is strong electrostatic interaction between particles and cytisine molecules, and on this basis, cytisine surface-imprinting can be smoothly performed. The surface-imprinted MIP-SASP/SiO2 has special recognition selectivity and excellent binding affinity for cytisine, and the selectivity coefficients of MIP-SASP/SiO2 particles for cytisine relative to matrine and oxymatrine, which were used as two contrast alkaloids, are 9.5 and 6.5, respectively.

  20. Pharmacophore modeling for anti-Chagas drug design using the fragment molecular orbital method.

    Directory of Open Access Journals (Sweden)

    Ryunosuke Yoshino

    Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that causes severe human health problems. To develop a new chemotherapeutic agent for the treatment of Chagas disease, we predicted a pharmacophore model for T. cruzi dihydroorotate dehydrogenase (TcDHODH by fragment molecular orbital (FMO calculation for orotate, oxonate, and 43 orotate derivatives.Intermolecular interactions in the complexes of TcDHODH with orotate, oxonate, and 43 orotate derivatives were analyzed by FMO calculation at the MP2/6-31G level. The results indicated that the orotate moiety, which is the base fragment of these compounds, interacts with the Lys43, Asn67, and Asn194 residues of TcDHODH and the cofactor flavin mononucleotide (FMN, whereas functional groups introduced at the orotate 5-position strongly interact with the Lys214 residue.FMO-based interaction energy analyses revealed a pharmacophore model for TcDHODH inhibitor. Hydrogen bond acceptor pharmacophores correspond to Lys43 and Lys214, hydrogen bond donor and acceptor pharmacophores correspond to Asn67 and Asn194, and the aromatic ring pharmacophore corresponds to FMN, which shows important characteristics of compounds that inhibit TcDHODH. In addition, the Lys214 residue is not conserved between TcDHODH and human DHODH. Our analysis suggests that these orotate derivatives should preferentially bind to TcDHODH, increasing their selectivity. Our results obtained by pharmacophore modeling provides insight into the structural requirements for the design of TcDHODH inhibitors and their development as new anti-Chagas drugs.

  1. Designing molecular dynamics simulations to shift populations of the conformational states of calmodulin.

    Directory of Open Access Journals (Sweden)

    Ayse Ozlem Aykut

    Full Text Available We elucidate the mechanisms that lead to population shifts in the conformational states of calcium-loaded calmodulin (Ca(2+-CaM. We design extensive molecular dynamics simulations to classify the effects that are responsible for adopting occupied conformations available in the ensemble of NMR structures. Electrostatic interactions amongst the different regions of the protein and with its vicinal water are herein mediated by lowering the ionic strength or the pH. Amino acid E31, which is one of the few charged residues whose ionization state is highly sensitive to pH differences in the physiological range, proves to be distinctive in its control of population shifts. E31A mutation at low ionic strength results in a distinct change from an extended to a compact Ca(2+-CaM conformation within tens of nanoseconds, that otherwise occur on the time scales of microseconds. The kinked linker found in this particular compact form is observed in many of the target-bound forms of Ca(2+-CaM, increasing the binding affinity. This mutation is unique in controlling C-lobe dynamics by affecting the fluctuations between the EF-hand motif helices. We also monitor the effect of the ionic strength on the conformational multiplicity of Ca(2+-CaM. By lowering the ionic strength, the tendency of nonspecific anions in water to accumulate near the protein surface increases, especially in the vicinity of the linker. The change in the distribution of ions in the vicinal layer of water allows N- and C- lobes to span a wide variety of relative orientations that are otherwise not observed at physiological ionic strength. E31 protonation restores the conformations associated with physiological environmental conditions even at low ionic strength.

  2. Molecular mechanics approach for design and conformational studies of macrocyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rohini,; Akbar, Rifat; Kanungo, B. K., E-mail: b.kanungo@gmail.com [Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal-148106 (India)

    2015-08-28

    Computational Chemistry has revolutionized way of viewing molecules at the quantum mechanical scale by allowing simulating various chemical scenarios that are not possible to study in a laboratory. The remarkable applications of computational chemistry have promoted to design and test of the effectiveness of various methods for searching the conformational space of highly flexible molecules. In this context, we conducted a series of optimization and conformational searches on macrocyclic based ligands, 9N3Me5Ox, (1,4,7-tris(5-methyl-8-hydroxyquinoline)-1,4,7-triazacyclononane) and 12N3Me5Ox, (1,5,9-tris(5-methyl-8-hydroxyquinoline)-1,5,9-triazacyclododecane) and studied their selectivity and coordination behavior with some lanthanide metal ions in molecular mechanics and semiempirical methods. The methods include both systematic and random conformational searches for dihedral angles, torsion angles and Cartesian coordinates. Structural studies were carried out by using geometry optimization, coordination scans and electronic properties were evaluated. The results clearly show that chair-boat conformational isomer of 9N3Me5Ox ligand is more stable due to lower eclipsing ethane interaction and form stronger adduct complexes with lanthanide metal ion. This is because of the fact that, in a central unit of 9N3 of the ligand form six endo type bonds out of nine. The rest of bonds have trans conformation. In contrast, for the adduct of 12N3Me5Ox, two C-C bonds have on eclipsed conformation, and others have synclinal and antiperiplanar confirmations. The distortion of the two eclipsed conformations may affect the yields and the stability of the complexes.

  3. Glucosamine-6-phosphate synthase, a novel target for antifungal agents. Molecular modelling studies in drug design.

    Science.gov (United States)

    Wojciechowski, Marek; Milewski, Sławomir; Mazerski, Jan; Borowski, Edward

    2005-01-01

    Fungal infections are a growing problem in contemporary medicine, yet only a few antifungal agents are used in clinical practice. In our laboratory we proposed the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase (EC 2.6.1.16) as a new target for antifungals. The structure of this enzyme consists of two domains, N-terminal and C-terminal ones, catalysing glutamine hydrolysis and sugar-phosphate isomerisation, respectively. In our laboratory a series of potent selective inhibitors of GlcN-6-P synthase have been designed and synthesised. One group of these compounds, including the most studied N3-(4-methoxyfumaroyl)-l-2,3-diaminopropanoic acid (FMDP), behave like glutamine analogs acting as active-site-directed inactivators, blocking the N-terminal, glutamine-binding domain of the enzyme. The second group of GlcN-6-P synthase inhibitors mimic the transition state of the reaction taking place in the C-terminal sugar isomerising domain. Surprisingly, in spite of the fact that glutamine is the source of nitrogen for a number of enzymes it turned out that the glutamine analogue FMDP and its derivatives are selective against GlcN-6-P synthase and they do not block other enzymes, even belonging to the same family of glutamine amidotransferases. Our molecular modelling studies of this phenomenon revealed that even within the family of related enzymes substantial differences may exist in the geometry of the active site. In the case of the glutamine amidotransferase family the glutamine binding site of GlcN-6-P synthase fits a different region of the glutamine conformational space than other amidotransferases. Detailed analysis of the interaction pattern for the best known, so far, inhibitor of the sugar isomerising domain, namely 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP), allowed us to suggest changes in the structure of the inhibitor that should improve the interaction pattern. The novel ligand was designed and synthesised. Biological experiments confirmed

  4. Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals.

    Science.gov (United States)

    Kobayashi, Hisataka; Longmire, Michelle R; Ogawa, Mikako; Choyke, Peter L

    2011-09-01

    In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references).

  5. Reactive Attachment Disorder of Infancy or Early Childhood

    OpenAIRE

    Richters, Dr. Margot Moser; Volkmar, Dr. Fred R.

    1994-01-01

    Since its introduction into DSM-Ill, reactive attachment disorder has stood curiously apart from other diagnoses for two reasons: it remains the only diagnosis designed for infants, and it requires the presence of a specific etiology. This paper describes the pattern of disturbances demonstrated by some children who meet DSM-Ill-R criteria for reactive attachment disorder. Three suggestions are made: (1) the sensitivity and specificity of the diagnostic concept may be enhanced by including cr...

  6. Theoretical design of the cyclic lipopeptide nanotube as a molecular channel in the lipid bilayer, molecular dynamics and quantum mechanics approach.

    Science.gov (United States)

    Khavani, Mohammad; Izadyar, Mohammad; Housaindokht, Mohammad Reza

    2015-10-14

    In this article, cyclic peptides (CP) with lipid substituents were theoretically designed. The dynamical behavior of the CP dimers and the cyclic peptide nanotube (CPNT) without lipid substituents in the solution (water and chloroform) during the 50 ns molecular dynamic (MD) simulations has been investigated. As a result, the CP dimers and CPNT in a non-polar solvent are more stable than in a polar solvent and CPNT is a good container for non-polar small molecules such as chloroform. The effect of the lipid substituents on the CP dimers and CPNT has been investigated in the next stage of our studies. Accordingly, these substituents increase the stability of the CP dimers and CPNT, significantly, in polar solvents. MM-PBSA and MM-GBSA calculations confirm that substitution has an important effect on the stability of the CP dimers and CPNT. Finally, the dynamical behavior of CPNT with lipid substituents in a fully hydrated DMPC bilayer shows the high ability of this structure for molecule transmission across the lipid membrane. This structure is stable enough to be used as a molecular channel. DFT calculations on the CP dimers in the gas phase, water and chloroform, indicate that H-bond formation is the driving force for dimerization. CP dimers are more stable in the gas phase in comparison to in solution. HOMO-LUMO orbital analysis indicates that the interaction of the CP units in the dimer structures is due to the molecular orbital interactions between the NH and CO groups.

  7. Long-term oxytocin administration enhances the experience of attachment.

    Science.gov (United States)

    Bernaerts, Sylvie; Prinsen, Jellina; Berra, Emmely; Bosmans, Guy; Steyaert, Jean; Alaerts, Kaat

    2017-04-01

    The neuropeptide 'oxytocin' (OT) is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. Previous studies showed that a single-dose of exogenously administered OT can affect trust and feelings of attachment insecurity. With the present study, we explored the effects of two weeks of daily OT administration on measures of state and trait attachment using a double-blind between-subjects randomized placebo-controlled design. In 40 healthy young adult men state and trait attachment were assessed before and after two weeks of daily intranasal OT (24 IU) or placebo using the State Adult Attachment Scale and the Inventory of Parent and Peer Attachment. Mood, social responsiveness and quality of life were additionally assessed as secondary outcome measures. Reductions in attachment avoidance and increases in reports of attachment toward peers were reported after two weeks of OT treatment. Further, treatment-induced changes were most pronounced for participants with less secure attachment towards their peers. indicating that normal variance at baseline modulated treatment response. OT treatment was additionally associated with changes in mood, indicating decreases in feelings of tension and (tentatively) anger in the OT group, not in the placebo group. Further, at the end of the two-week trial, both treatment groups (OT, placebo) reported to experience an increase in social responsiveness and quality of life, but the effects were only specific to the OT-treatment in terms of reports on 'social motivation'. In summary, the observed improvements on state and trait dimensions of attachment after a multiple-dose treatment with OT provide further evidence in support of a pivotal role of OT in promoting the experience of attachment.

  8. Molecular Cloning of cpcU and Heterodimeric Bilin Lyase Activity Analysis of CpcU and CpcS for Attachment of Phycocyanobilin to Cys-82 on the β-Subunit of Phycocyanin in Arthrospira platensis FACHB314

    Directory of Open Access Journals (Sweden)

    Fei Wu

    2016-03-01

    Full Text Available A new bilin lyase gene cpcU was cloned from Arthrospira platensis FACHB314 to study the assembly of the phycocyanin β-Subunit. Two recombinant plasmids, one contained the phycocyanobilin (PCB producing genes (hoxI and pcyA, while the other contained the gene of the β-Subunit of phycobiliprotein (cpcB and the lyase gene (cpcU, cpcS, or cpcU/S were constructed and separately transferred into Escherichia coli in order to test the activities of relevant lyases for catalyzing PCB addition to CpcB during synthesizing fluorescent β-PC of A. platensis FACHB314. The fluorescence intensity examination showed that Cys-82 maybe the active site for the β-Subunit binding to PCBs and the attachment could be carried out by CpcU, CpcS, or co-expressed cpcU/S in A. platensis FACHB314.

  9. Molecular Cloning of cpcU and Heterodimeric Bilin Lyase Activity Analysis of CpcU and CpcS for Attachment of Phycocyanobilin to Cys-82 on the β-Subunit of Phycocyanin in Arthrospira platensis FACHB314.

    Science.gov (United States)

    Wu, Fei; Zang, Xiaonan; Zhang, Xuecheng; Zhang, Ran; Huang, Xiaoyun; Hou, Lulu; Jiang, Minjie; Liu, Chang; Pang, Chunhong

    2016-03-16

    A new bilin lyase gene cpcU was cloned from Arthrospira platensis FACHB314 to study the assembly of the phycocyanin β-Subunit. Two recombinant plasmids, one contained the phycocyanobilin (PCB) producing genes (hoxI and pcyA), while the other contained the gene of the β-Subunit of phycobiliprotein (cpcB) and the lyase gene (cpcU, cpcS, or cpcU/S) were constructed and separately transferred into Escherichia coli in order to test the activities of relevant lyases for catalyzing PCB addition to CpcB during synthesizing fluorescent β-PC of A. platensis FACHB314. The fluorescence intensity examination showed that Cys-82 maybe the active site for the β-Subunit binding to PCBs and the attachment could be carried out by CpcU, CpcS, or co-expressed cpcU/S in A. platensis FACHB314.

  10. Site-specific integration of the temperate bacteriophage phi adh into the Lactobacillus gasseri chromosome and molecular characterization of the phage (attP) and bacterial (attB) attachment sites.

    Science.gov (United States)

    Raya, R R; Fremaux, C; De Antoni, G L; Klaenhammer, T R

    1992-01-01

    The temperate bacteriophage phi adh integrates its genome into the chromosomal DNA of Lactobacillus gasseri ADH by a site-specific recombination process. Southern hybridization analysis of BclI-digested genomic DNA from six relysogenized derivatives of the prophage-cured strain NCK102 displayed phage-chromosomal junction fragments identical to those of the lysogenic parent. The phi adh attachment site sequence, attP, was located within a 365-bp EcoRI-HindIII fragment of phage phi adh. This fragment was cloned and sequenced. DNA sequence analysis revealed striking features common to the attachment sites of other site-specific recombination systems: five direct repeats of the sequence TGTCCCTTTT(C/T) and a 14-bp inverted repeat. Oligonucleotides derived from the sequence of the attP-containing fragment enabled us to amplify predicted junction fragment sequences and thus to identify attL, attR, and attB. The core region was defined as the 16-bp sequence TACACTTCTTAGGAGG. Phage-encoded functions essential for site-specific insertion of phage phi adh were located in a 4.5-kb BclI fragment. This fragment was cloned in plasmid pSA34 to generate the insertional vector pTRK182. Plasmid pTRK182 was introduced into L. gasseri NCK102 by electroporation. Hybridization analysis showed that a single copy of pTRK182 had integrated at the attB site of the NCK102 erythromycin-resistant transformants. This is the first site-specific recombination system described in lactobacilli, as well as the first attP-based site-specific integration vector constructed for L. gasseri ADH. Images PMID:1512192

  11. 多机电力系统中光伏发电厂附加稳定器的设计%Design of astabilizer attached to a grid-connected PV power plant in a multi-machine power system

    Institute of Scientific and Technical Information of China (English)

    杜文娟; 王海风; 曹军

    2011-01-01

    在未来电力系统中,光伏发电厂将是一种重要的可再生电源.光伏发电厂接入未来电力系统将会影响输电系统稳定运行和控制.提出一种多机电力系统中光伏发电厂稳定器的设计新方法.首先搭建接入电网的光伏发电厂局部线性化模型.给出在光伏发电厂接入地点附近线路上发生低频功率振荡与附加稳定器控制的关系.在此局部线性化模型基础上,演示如何使用经典的相位补偿法设计附加稳定器,向线路低频功率振荡提供正阻尼.该方法无需获得和验证全多机电力系统的运行和参数信息,就能进行稳定器的设计,是一种简单、局部化的设计方法.实例分析验证了该方法的有效性,即通过在光伏发电厂上附加稳定器,可以有效帮助提高电力系统的稳定性.%Photovoltaic (PV) generation will be one of the main renewable power sources in future power systems.Grid connection of PV generation can facilitate efficient and large-scale applications,which can affect significantly the operation and control of power transmission in future.This paper presents a novel method to design a stabilizer attached to a grid-connected PV power plant in a multi-machine power system.Firstly in the paper,a localized model of the grid-connected PV power plant is derived.The model gives the relationship between power oscillations along the transmission lines where the PV power plant is connected and the stabilizing control of the stabilizer.Based on the localized model,it is demonstrated that the conventional phase compensation method can be applied to design the stabilizer to provide positive damping to the line power oscillations.Hence the proposed application of the phase compensation method to design the stabilizer is both simple and localized,as it does not need to obtain and validate the information and parameters of the entire multi-machine power system.In the paper,an example fourmachine power system

  12. The impact of molecular dynamics on drug design: applications for the characterization of ligand-macromolecule complexes.

    Science.gov (United States)

    Mortier, Jérémie; Rakers, Christin; Bermudez, Marcel; Murgueitio, Manuela S; Riniker, Sereina; Wolber, Gerhard

    2015-06-01

    Among all tools available to design new drugs, molecular dynamics (MD) simulations have become an essential technique. Initially developed to investigate molecular models with a limited number of atoms, computers now enable investigations of large macromolecular systems with a simulation time reaching the microsecond range. The reviewed articles cover four years of research to give an overview on the actual impact of MD on the current medicinal chemistry landscape with a particular emphasis on studies of ligand-protein interactions. With a special focus on studies combining computational approaches with data gained from other techniques, this review shows how deeply embedded MD simulations are in drug design strategies and articulates what the future of this technique could be.

  13. Design of a nanomechanical fluid control valve based on functionalized silicon cantilevers: coupling molecular mechanics with classical engineering design

    OpenAIRE

    Santiago D. Solares; Blanco, Mario; Goddard, William A.

    2004-01-01

    Process engineering design relies on a host of mechanical devices that enable transport phenomena to take place under controlled conditions. These devices include pipes, valves, pumps, chemical reactors, heat exchangers, packed columns, etc. Mass, energy, and momentum transfer will also be essential phenomena in nanoprocess engineering, particularly at the interface between micro- and nanodevices. Control valves are one of the most fundamental components. In this paper we explore the design o...

  14. Cladding Attachment Over Thick Exterior Insulating Sheathing

    Energy Technology Data Exchange (ETDEWEB)

    Baker, P. [Building Science Corporation, Somerville, MA (United States); Eng, P. [Building Science Corporation, Somerville, MA (United States); Lepage, R. [Building Science Corporation, Somerville, MA (United States)

    2014-01-01

    The addition of insulation to the exterior of buildings is an effective means of increasing the thermal resistance of both wood framed walls as well as mass masonry wall assemblies. For thick layers of exterior insulation (levels greater than 1.5 inches), the use of wood furring strips attached through the insulation back to the structure has been used by many contractors and designers as a means to provide a convenient cladding attachment location (Straube and Smegal 2009, Pettit 2009, Joyce 2009, Ueno 2010). The research presented in this report is intended to help develop a better understanding of the system mechanics involved and the potential for environmental exposure induced movement between the furring strip and the framing. BSC sought to address the following research questions: 1.What are the relative roles of the mechanisms and the magnitudes of the force that influence the vertical displacement resistance of the system? 2.Can the capacity at a specified deflection be reliably calculated using mechanics based equations? 3.What are the impacts of environmental exposure on the vertical displacement of furring strips attached directly through insulation back to a wood structure?

  15. Cladding Attachment Over Thick Exterior Insulating Sheathing

    Energy Technology Data Exchange (ETDEWEB)

    Baker, P.; Eng, P.; Lepage, R.

    2014-01-01

    The addition of insulation to the exterior of buildings is an effective means of increasing the thermal resistance of both wood framed walls as well as mass masonry wall assemblies. For thick layers of exterior insulation (levels greater than 1.5 inches), the use of wood furring strips attached through the insulation back to the structure has been used by many contractors and designers as a means to provide a convenient cladding attachment location (Straube and Smegal 2009, Pettit 2009, Joyce 2009, Ueno 2010). The research presented in this report is intended to help develop a better understanding of the system mechanics involved and the potential for environmental exposure induced movement between the furring strip and the framing. BSC sought to address the following research questions: 1. What are the relative roles of the mechanisms and the magnitudes of the force that influence the vertical displacement resistance of the system? 2. Can the capacity at a specified deflection be reliably calculated using mechanics based equations? 3. What are the impacts of environmental exposure on the vertical displacement of furring strips attached directly through insulation back to a wood structure?

  16. Rational design of two-dimensional molecular donor-acceptor nanostructure arrays

    Science.gov (United States)

    Zhang, Jia Lin; Zhong, Shu; Zhong, Jian Qiang; Niu, Tian Chao; Hu, Wen Ping; Wee, Andrew Thye Shen; Chen, Wei

    2015-02-01

    The construction of long-range ordered organic donor-acceptor nanostructure arrays over microscopic areas supported on solid substrates is one of the most challenging tasks towards the realization of molecular nanodevices. They can also be used as ideal model systems to understand light induced charge transfer, charge separation and energy conversion processes and mechanisms at the nanometer scale. The aim of this paper is to highlight recent advances and progress in this topic. Special attention is given to two different strategies for the construction of organic donor-acceptor nanostructure arrays, namely (i) molecular self-assembly on artificially patterned or pre-defined molecular surface nanotemplates and (ii) molecular nanostructure formation steered via directional and selective intermolecular interactions. The interfacial charge transfer and the energy level alignment of these donor-acceptor nanostructures are also discussed.

  17. Use of the adult attachment projective picture system in psychodynamic psychotherapy with a severely traumatized patient.

    Science.gov (United States)

    George, Carol; Buchheim, Anna

    2014-01-01

    The following case study is presented to facilitate an understanding of how the attachment information evident from Adult Attachment Projective Picture System (AAP) assessment can be integrated into a psychodynamic perspective in making therapeutic recommendations that integrate an attachment perspective. The Adult Attachment Projective Picture System (AAP) is a valid representational measure of internal representations of attachment based on the analysis of a set of free response picture stimuli designed to systematically activate the attachment system (George and West, 2012). The AAP provides a fruitful diagnostic tool for psychodynamic-oriented clinicians to identify attachment-based deficits and resources for an individual patient in therapy. This paper considers the use of the AAP with a traumatized patient in an inpatient setting and uses a case study to illustrate the components of the AAP that are particularly relevant to a psychodynamic conceptualization. The paper discusses also attachment-based recommendations for intervention.

  18. Molecular mechanisms and design principles for promiscuous inhibitors to avoid drug resistance: lessons learned from HIV-1 protease inhibition.

    Science.gov (United States)

    Shen, Yang; Radhakrishnan, Mala L; Tidor, Bruce

    2015-02-01

    Molecular recognition is central to biology and ranges from highly selective to broadly promiscuous. The ability to modulate specificity at will is particularly important for drug development, and discovery of mechanisms contributing to binding specificity is crucial for our basic understanding of biology and for applications in health care. In this study, we used computational molecular design to create a large dataset of diverse small molecules with a range of binding specificities. We then performed structural, energetic, and statistical analysis on the dataset to study molecular mechanisms of achieving specificity goals. The work was done in the context of HIV-1 protease inhibition and the molecular designs targeted a panel of wild-type and drug-resistant mutant HIV-1 protease structures. The analysis focused on mechanisms for promiscuous binding to bind robustly even to resistance mutants. Broadly binding inhibitors tended to be smaller in size, more flexible in chemical structure, and more hydrophobic in nature compared to highly selective ones. Furthermore, structural and energetic analyses illustrated mechanisms by which flexible inhibitors achieved binding; we found ligand conformational adaptation near mutation sites and structural plasticity in targets through torsional flips of asymmetric functional groups to form alternative, compensatory packing interactions or hydrogen bonds. As no inhibitor bound to all variants, we designed small cocktails of inhibitors to do so and discovered that they often jointly covered the target set through mechanistic complementarity. Furthermore, using structural plasticity observed in experiments, and potentially in simulations, is suggested to be a viable means of designing adaptive inhibitors that are promiscuous binders.

  19. Analog series-based scaffolds: computational design and exploration of a new type of molecular scaffolds for medicinal chemistry

    Science.gov (United States)

    Dimova, Dilyana; Stumpfe, Dagmar; Hu, Ye; Bajorath, Jürgen

    2016-01-01

    Aim: Computational design of and systematic search for a new type of molecular scaffolds termed analog series-based scaffolds. Materials & methods: From currently available bioactive compounds, analog series were systematically extracted, key compounds identified and new scaffolds isolated from them. Results: Using our computational approach, more than 12,000 scaffolds were extracted from bioactive compounds. Conclusion: A new scaffold definition is introduced and a computational methodology developed to systematically identify such scaffolds, yielding a large freely available scaffold knowledge base.

  20. Electron attachment to indole and related molecules

    Energy Technology Data Exchange (ETDEWEB)

    Modelli, Alberto, E-mail: alberto.modelli@unibo.it [Dipartimento di Chimica “G. Ciamician”, Universitá di Bologna, via Selmi 2, 40126 Bologna (Italy); Centro Interdipartimentale di Ricerca in Scienze Ambientali (CIRSA), Universitá di Bologna, via S. Alberto 163, 48123 Ravenna (Italy); Jones, Derek, E-mail: d.jones@isof.cnr.it [ISOF, Istituto per la Sintesi Organica e la Fotoreattività, C.N.R., via Gobetti 101, 40129 Bologna (Italy); Pshenichnyuk, Stanislav A., E-mail: sapsh@anrb.ru [Institute of Molecule and Crystal Physics, Ufa Research Centre, Russian Academy of Sciences, Prospekt Oktyabrya 151, 450075 Ufa (Russian Federation)

    2013-11-14

    Gas-phase formation of temporary negative ion states via resonance attachment of low-energy (0–6 eV) electrons into vacant molecular orbitals of indoline (I), indene (II), indole (III), 2-methylen-1,3,3-trimethylindoline (IV), and 2,3,3-trimethyl-indolenine (V) was investigated for the first time by electron transmission spectroscopy (ETS). The description of their empty-level structures was supported by density functional theory and Hartree-Fock calculations, using empirically calibrated linear equations to scale the calculated virtual orbital energies. Dissociative electron attachment spectroscopy (DEAS) was used to measure the fragment anion yields generated through dissociative decay channels of the parent molecular anions of compounds I-V, detected with a mass filter as a function of the incident electron energy in the 0–14 eV energy range. The vertical and adiabatic electron affinities were evaluated at the B3LYP/6-31+G(d) level as the anion/neutral total energy difference. The same theoretical method is also used for evaluation of the thermodynamic energy thresholds for production of the negative fragments observed in the DEA spectra. The loss of a hydrogen atom from the parent molecular anion ([M-H]{sup −}) provides the most intense signal in compounds I-IV. The gas-phase DEAS data can provide support for biochemical reaction mechanisms in vivo involving initial hydrogen abstraction from the nitrogen atom of the indole moiety, present in a variety of biologically important molecules.

  1. "New drug" designations for new therapeutic entities: new active substance, new chemical entity, new biological entity, new molecular entity.

    Science.gov (United States)

    Branch, Sarah K; Agranat, Israel

    2014-11-13

    This Perspective addresses ambiguities in designations of "new drugs" intended as new therapeutic entities (NTEs). Designation of an NTE as a new drug is significant, as it may confer regulatory exclusivity, an important incentive for development of novel compounds. Such designations differ between jurisdictions according to their drug laws and drug regulations. Chemical, biological, and innovative drugs are addressed in turn. The terms new chemical entity (NCE), new molecular entity (NME), new active substance (NAS), and new biological entity (NBE) as applied in worldwide jurisdictions are clarified. Differences between them are explored through case studies showing why new drugs have different periods of exclusivity in different jurisdictions or none at all. Finally, this Perspective recommends that in future, for the purpose of new drug compilations, NME is used for a new chemical drug, NBE for a new biological drug, and the combined designation NTE should refer to either an NME or an NBE.

  2. Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal Farnesoid X Receptor (FXR) Antagonists: Molecular Basis of FXR Antagonism.

    Science.gov (United States)

    Huang, Huang; Si, Pei; Wang, Lei; Xu, Yong; Xu, Xin; Zhu, Jin; Jiang, Hualiang; Li, Weihua; Chen, Lili; Li, Jian

    2015-07-01

    Farnesoid X receptor (FXR) plays an important role in the regulation of cholesterol, lipid, and glucose metabolism. Recently, several studies on the molecular basis of FXR antagonism have been reported. However, none of these studies employs an FXR antagonist with nonsteroidal scaffold. On the basis of our previously reported FXR antagonist with a trisubstituted isoxazole scaffold, a novel nonsteroidal FXR ligand was designed and used as a lead for structural modification. In total, 39 new trisubstituted isoxazole derivatives were designed and synthesized, which led to pharmacological profiles ranging from agonist to antagonist toward FXR. Notably, compound 5s (4'-[(3-{[3-(2-chlorophenyl)-5-(2-thienyl)isoxazol-4-yl]methoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid), containing a thienyl-substituted isoxazole ring, displayed the best antagonistic activity against FXR with good cellular potency (IC50 =12.2 ± 0.2 μM). Eventually, this compound was used as a probe in a molecular dynamics simulation assay. Our results allowed us to propose an essential molecular basis for FXR antagonism, which is consistent with a previously reported antagonistic mechanism; furthermore, E467 on H12 was found to be a hot-spot residue and may be important for the future design of nonsteroidal antagonists of FXR.

  3. Nano-design of quantum dot-based photocatalysts for hydrogen generation using advanced surface molecular chemistry

    KAUST Repository

    Yu, Weili

    2015-01-01

    Efficient photocatalytic hydrogen generation in a suspension system requires a sophisticated nano-device that combines a photon absorber with effective redox catalysts. This study demonstrates an innovative molecular linking strategy for fabricating photocatalytic materials that allow effective charge separation of excited carriers, followed by efficient hydrogen evolution. The method for the sequential replacement of ligands with appropriate molecules developed in this study tethers both quantum dots (QDs), as photosensitizers, and metal nanoparticles, as hydrogen evolution catalysts, to TiO2 surfaces in a controlled manner at the nano-level. Combining hydrophobic and hydrophilic interactions on the surface, CdSe-ZnS core-shell QDs and an Au-Pt alloy were attached to TiO2 without overlapping during the synthesis. The resultant nano-photocatalysts achieved substantially high-performance visible-light-driven photocatalysis for hydrogen evolution. All syntheses were conducted at room temperature and in ambient air, providing a promising route for fabricating visible-light-responsive photocatalysts.

  4. Pyrroloaryls and pyrroloheteroaryls: Inhibitors of the HIV fusion/attachment, reverse transcriptase and integrase.

    Science.gov (United States)

    Patel, Rahul V; Park, Se Won

    2015-09-01

    Heterocyclic compounds execute a very important role in drug design and discovery. This article provides the basic milestones of the research for pyrroloaryl and pyrroloheteroaryl based components targeting HIV viral replication cycle. Anti-HIV activity is elaborated for several classes of pyrrolo-compounds as pyrrolopyridines, pyrrolopyrimidines, pyrrolopyridazines, pyrrolobenzodiazepinones, pyrrolobenzothiazepines, pyrrolobenzoxazepinones, pyrrolophenanthridines, pyrroloquinoxalines, pyrrolotriazines, pyrroloquinolines, pyrrolopyrazinones, pyrrolothiatriazines, arylthiopyrroles and pyrrolopyrazolones targeting two essential HIV enzymes, reverse transcriptase and integrase as well as attachment/fusion of HIV virons to the host CD-4 cell. Such attempts were resulted in a discovery of highly potent anti-HIV agents suitable for clinical trials, for example, BMS-378806, BMS-585248, BMS-626529, BMS-663068, BMS-488043 and BMS-663749, etc. as anti-HIV attachment agents, triciribine, QX432, BI-1 and BI-2 as HIV RT inhibitors which are in preclinical or clinical development. Mechanism of action of compounds presented in this article towards the suppression of HIV attachment/fusion as well as against the activities of HIV enzymes reverse transcriptase and integrase has been discussed. Relationships of new compounds' molecular framework and HIV viral target has been overviewed in order to facilitate further construction of promising anti-HIV agents in future drug discovery process.

  5. Hamiltonian Dynamics of Preferential Attachment

    CERN Document Server

    Zuev, Konstantin; Krioukov, Dmitri

    2015-01-01

    Prediction and control of network dynamics are grand-challenge problems in network science. The lack of understanding of fundamental laws driving the dynamics of networks is among the reasons why many practical problems of great significance remain unsolved for decades. Here we study the dynamics of networks evolving according to preferential attachment, known to approximate well the large-scale growth dynamics of a variety of real networks. We show that this dynamics is Hamiltonian, thus casting the study of complex networks dynamics to the powerful canonical formalism, in which the time evolution of a dynamical system is described by Hamilton's equations. We derive the explicit form of the Hamiltonian that governs network growth in preferential attachment. This Hamiltonian turns out to be nearly identical to graph energy in the configuration model, which shows that the ensemble of random graphs generated by preferential attachment is nearly identical to the ensemble of random graphs with scale-free degree d...

  6. Rational Design of Molecular Gelator - Solvent Systems Guided by Solubility Parameters

    Science.gov (United States)

    Lan, Yaqi

    Self-assembled architectures, such as molecular gels, have attracted wide interest among chemists, physicists and engineers during the past decade. However, the mechanism behind self-assembly remains largely unknown and no capability exists to predict a priori whether a small molecule will gelate a specific solvent or not. The process of self-assembly, in molecular gels, is intricate and must balance parameters influencing solubility and those contrasting forces that govern epitaxial growth into axially symmetric elongated aggregates. Although the gelator-gelator interactions are of paramount importance in understanding gelation, the solvent-gelator specific (i.e., H-bonding) and nonspecific (dipole-dipole, dipole-induced and instantaneous dipole induced forces) intermolecular interactions are equally important. Solvent properties mediate the self-assembly of molecular gelators into their self-assembled fibrillar networks. Herein, solubility parameters of solvents, ranging from partition coefficients (logP), to Henry's law constants (HLC), to solvatochromic ET(30) parameters, to Kamlet-Taft parameters (beta, alpha and pi), to Hansen solubility parameters (deltap, deltad, deltah), etc., are correlated with the gelation ability of numerous classes of molecular gelators. Advanced solvent clustering techniques have led to the development of a priori tools that can identify the solvents that will be gelled and not gelled by molecular gelators. These tools will greatly aid in the development of novel gelators without solely relying on serendipitous discoveries.

  7. Attachment Processes in Eating Disorder and Depression.

    Science.gov (United States)

    Cole-Detke, Holland; Kobak, Roger

    1996-01-01

    Examines the relationship between attachment strategies and symptom reporting among college women (N=61). The Adult Attachment Interview (AAI) was administered and interview transcripts were rated with the Attachment Interview Q-Sort. Findings support the hypothesis that secondary or defensive attachment strategies predispose individuals toward…

  8. Attachment to Inanimate Objects and Early Childcare: A Twin Study

    Directory of Open Access Journals (Sweden)

    Keren eFortuna

    2014-05-01

    Full Text Available Extensive nonmaternal childcare plays an important role in children's development. This study examined a potential coping mechanism for dealing with daily separation from caregivers involved in childcare experience—children's development of attachments toward inanimate objects. We employed the twin design to estimate relative environmental and genetic contributions to the presence of object attachment, and assess whether childcare explains some of the environmental variation in this developmental phenomenon. Mothers reported about 1122 3-year-old twin pairs. Variation in object attachment was accounted for by heritability (48% and shared environment (48%, with childcare quantity accounting for 2.2% of the shared environment effect. Children who spent half-days in childcare were significantly less likely to attach to objects relative to children who attended full-day childcare.

  9. Light-driven rotary molecular motors without point chirality: a minimal design.

    Science.gov (United States)

    Wang, Jun; Oruganti, Baswanth; Durbeej, Bo

    2017-03-08

    A fundamental requirement for achieving photoinduced unidirectional rotary motion about an olefinic bond in a molecular motor is that the potential energy surface of the excited state is asymmetric with respect to clockwise and counterclockwise rotations. In most available light-driven rotary molecular motors, such asymmetry is guaranteed by the presence of a stereocenter. Here, we present non-adiabatic molecular dynamics simulations based on multiconfigurational quantum chemistry to demonstrate that this chiral feature is not essential for inducing unidirectional rotary motion in molecules that incorporate a cyclohexenylidene moiety into a protonated Schiff-base framework. Rather, the simulations show that it is possible to exploit the intrinsic asymmetry of the puckered cyclohexenylidene to control the direction of photoinduced rotation.

  10. Structural Interfaces and Attachments in Biology

    CERN Document Server

    Birman, Victor; Genin, Guy

    2013-01-01

    Attachment of dissimilar materials in engineering and surgical practice is a perennial challenge. Bimaterial attachment sites are common locations for injury, repeated injury, and mechanical failure. Nature presents several highly effective solutions to the challenge of bimaterial attachment that differ from those found in engineering practice. Structural Interfaces and Attachments in Biology describes the attachment of dissimilar materials from multiple perspectives. The text will simultaneously elucidate natural bimaterial attachments and outline engineering principles underlying successful attachments to the communities of tissue engineers and surgeons. Included an in-depth analysis of the biology of attachments in the body and mechanisms by which robust attachments are formed, a review of current concepts of attaching dissimilar materials in surgical practice and a discussion of bioengineering approaches that are currently being developed. This book also: Provides the first comprehensive treatment of phys...

  11. Remote handling assessment of attachment concepts for DEMO blanket segments

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, Daniel, E-mail: daniel.iglesias@ccfe.ac.uk [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Bastow, Roger; Cooper, Dave; Crowe, Robert; Middleton-Gear, Dave [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Sibois, Romain [VTT, Technical Research Centre of Finland, Industrial Systems, ROViR, Tampere (Finland); Carloni, Dario [Institute of Neutron Physics and Reactor Technology, Karlsruhe Institute of Technology (KIT) (Germany); Vizvary, Zsolt; Crofts, Oliver [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Harman, Jon [EFDA Close Support Unit Garching, Boltzmannstaße 2, D-85748 Garching bei München (Germany); Loving, Antony [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom)

    2015-10-15

    Highlights: • Challenges are identified for the remote handling of blanket segments’ attachments. • Two attachment design approaches are assessed for remote handling (RH) feasibility. • An alternative is proposed, which potentially simplifies and speeds-up RH operations. • Up to three different assemblies are proposed for the remote handling of the attachments. • Proposed integrated design of upper port is compatible with the attachment systems. - Abstract: The replacement strategy of the massive Multi-Module Blanket Segments (MMS) is a key driver in the design of several DEMO systems. These include the blankets themselves, the vacuum vessel (VV) and its ports and the Remote Maintenance System (RMS). Common challenges to any blanket attachment system have been identified, such as the need for applying a preload to the MMS manifold, the effects of the decay heat and several uncertainties related to permanent deformations when removing the blanket segments after service. The WP12 kinematics of the MMS in-vessel transportation was adapted to the requirements of each of the supports during 2013 and 2014 design activities. The RM equipment envisaged for handling attachments and earth connections may be composed of up to three different assemblies. An In-Vessel Mover at the divertor level handles the lower support and earth bonding, and could stabilize the MMS during transportation. A Shield Plug crane with a 6 DoF manipulator operates the upper attachment and earth straps. And a Vertical Maintenance Crane is responsible for the in-vessel MMS transportation and can handle the removable upper support pins. A final proposal is presented which can potentially reduce the number of required systems, at the same time that speeds-up the RMS global operations.

  12. Self-assembly, redox activity, and charge transport of functional surface nano-architectures by molecular design

    Science.gov (United States)

    Skomski, Daniel

    Surface-assisted molecular self-assembly is a promising strategy to program the structure and chemical state of atoms and molecules in nano-architectures to achieve a specific function. The experiments described in this thesis demonstrate that the design and programming of basic organic components leads to desired characteristics by self-assembly. The fabrication of uniform single-site metal centers at surfaces, important for high selectivity in next-generation catalysts, was accomplished by coordination to redox non-innocent phenanthroline and tetrazine-based ligands. These examples were the first demonstrating tuning of the metal oxidation state in surface coordination architectures through rational ligand design. The molecular-scale coordination architectures were the first formed from chromium and vanadium, and the first from platinum in a non-porphyrin system. The first mixed valence metal-ligand surface structure was fabricated that attained the same ligand coordination number for all metal sites. A new surface reaction method was demonstrated between an inexpensive sodium chloride reagent and carboxylate ligands. High-temperature, molecular-resolution microscopy and spectroscopy of the ordered metal-organic structures demonstrated thermal stability up to 300 °C, the highest molecular-level thermal stability in organic surface nanostructures yet achieved, making such systems potential candidates for moderate-temperature catalytic reactions. Molecular self-assembly was expanded into organic semiconductor thin films. In a two-component, bi-layered system, hydrogen bonding between carboxylates and carboxylic acid-substituted thiophenes was utilized, yielding the first real-space images of phenyl-thiophene stacking. In a one-component system, multiple donor-acceptor pi-pi contacts between phenyltriazole building blocks accomplished assembly of flat-lying molecules from a surface with molecular-scale precision through more than twenty molecular layers. Sufficient

  13. How the Molecular Packing Affects the Room Temperature Phosphorescence in Pure Organic Compounds: Ingenious Molecular Design, Detailed Crystal Analysis, and Rational Theoretical Calculations.

    Science.gov (United States)

    Xie, Yujun; Ge, Yuwei; Peng, Qian; Li, Conggang; Li, Qianqian; Li, Zhen

    2017-02-21

    Long-lived phosphorescence at room temperature (RTP) from pure organic molecules is rare. Recent research reveals various crystalline organic molecules can realize RTP with lifetimes extending to the magnitude of second. There is little research on how molecular packing affecting RTP. Three compounds are designed with similar optical properties in solution, but tremendously different solid emission characteristics. By investigating the molecular packing arrangement in single crystals, it is found that the packing style of the compact face to face favors of long phosphorescence lifetime and high photoluminescence efficiency, with the lifetime up to 748 ms observed in the crystal of CPM ((9H-carbazol-9-yl)(phenyl)methanone). Theoretical calculation analysis also reveals this kind of packing style can remarkably reduce the singlet excited energy level and prompt electron communication between dimers. Surprisingly, CPM has two very similar single crystals, labeled as CPM and CPM-A, with almost identical crystal data, and the only difference is that molecules in CPM-A crystal take a little looser packing arrangement. X-ray diffraction and cross-polarization under magic spinning (13) C NMR spectra double confirm that they are different crystals. Interestingly, CPM-A crystal shows negligible RTP compared to the CPM crystal, once again proving that the packing style is critical to the RTP property.

  14. Bio-rational design of photosystem Ⅱ inhibitors (Ⅷ)——Molecular design, synthesis and inhibitory activity of acrylates (acrylamides)

    Institute of Scientific and Technical Information of China (English)

    刘华银; 沙印林; 谭惠芬; 杨华铮; 来鲁华

    1999-01-01

    Molecular modeling of acrylates (acrylamides) with D1 protein of Pisum sativum is presented. Studies show that the binding force mainly includes H-bond interaction, Van der Waals and π-ring stacking interaction. It was found that SER 268 in D1 protein might be an important binding site. It is important for high inhibitory activity of compounds whether an electronegative atom in alkyl of ester linkage could make H-bond interaction with SER 268 in D1 protein. Thus some new acrylates (acrylamides) were designed and synthesized, Bioassay indicated that these new compounds showed expected Hill reaction inhibitory activity.

  15. WEAVING THE FABRIC OF ATTACHMENT

    Directory of Open Access Journals (Sweden)

    Lindsay Stewart

    2011-09-01

    Full Text Available This article is the Keynote Address given at the 5th International Integrative Psychotherapy Association Conference in Vichy, France, April 21, 2011. In the article author describes development of secure attachment with the help of the case study.

  16. Adult attachment and psychosocial functioning

    NARCIS (Netherlands)

    Pielage, Suzanne Brenda

    2006-01-01

    In the trilogy Attachment, Separation and Loss (1969, 1973, 1980), Bowlby theorized that early experiences with caregivers affect the quality of individuals’ later (romantic) relationships and, consequently, their mental health. The current thesis set out to examine the relationships between adult a

  17. Design, synthesis, crystal structure, insecticidal activity, molecular docking, and QSAR studies of novel N3-substituted imidacloprid derivatives.

    Science.gov (United States)

    Wang, Mei-Juan; Zhao, Xiao-Bo; Wu, Dan; Liu, Ying-Qian; Zhang, Yan; Nan, Xiang; Liu, Huanxiang; Yu, Hai-Tao; Hu, Guan-Fang; Yan, Li-Ting

    2014-06-18

    Three novel series of N3-substituted imidacloprid derivatives were designed and synthesized, and their structures were identified on the basis of satisfactory analytical and spectral ((1)H NMR, (13)C NMR, MS, elemental analysis, and X-ray) data. Preliminary bioassays indicated that all of the derivatives exhibited significant insecticidal activities against Aphis craccivora, with LC50 values ranging from 0.00895 to 0.49947 mmol/L, and the insecticidal activities of some of them were comparable to those of the control imidacloprid. Some key structural features related to their insecticidal activities were identified, and the binding modes between target compounds and nAChR model were also further explored by molecular docking. By comparing the interaction features of imidacloprid and compound 26 with highest insecticidal activity, the origin of the high insecticidal activity of compound 26 was identified. On the basis of the conformations generated by molecular docking, a satisfactory 2D-QSAR model with six selected descriptors was built using genetic algorithm-multiple linear regression (GA-MLR) method. The analysis of the built model showed the molecular size, shape, and the ability to form hydrogen bond were important for insecticidal potency. The information obtained in the study will be very helpful for the design of new derivatives with high insecticidal activities.

  18. Sensitivity analysis of Computer-aided molecular design problem for the development of novel working fluids for power cycles

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    allows the ranking ofsignificance of properties and also the identification of a set of properties which are relevant for the design of a workingfluids.In this study the CAMD problem for the development of novel working fluids for organic Rankine cycles (ORC) isformulated as a mathematical optimization...... technical tool to convert this waste heat into usable energy. So far the low-temperature heat cannot be utilized efficiently for electricity generation.In order to optimize the heat transfer process and the power generation, the influence of the working fluid, the cycledesigns and the operating conditions...... is vital. Multi-criteria database search and Computer Aided Molecular Design(CAMD) can be applied to generate, test and evaluate promising pure component/mixture candidate as process fluids to help optimize cycle design and performance. The problem formulation for the development of novel working fluids...

  19. Designing and Implementing a Hands-On, Inquiry-Based Molecular Biology Course

    Science.gov (United States)

    Regassa, Laura B.; Morrison-Shetlar, Alison I.

    2007-01-01

    Inquiry-based learning was used to enhance an undergraduate molecular biology course at Georgia Southern University, a primarily undergraduate institution in rural southeast Georgia. The goal was to use a long-term, in-class project to accelerate higher-order thinking, thereby enabling students to problem solve and apply their knowledge to novel…

  20. Preparation of melamine molecularly imprinted polymer by computer-aided design.

    Science.gov (United States)

    Wang, Yan; Liu, Jun-Bo; Tang, Shan-Shan; Jin, Rui-Fa

    2015-08-01

    Melamine was chosen as template, methacrylic acid was chosen as functional monomer, and divinylbenzene, ethylene glycol dimethacrylate, trimethylolpropane trimethylacrylate were chosen as cross-linking agents, respectively. The WB97XD/6-31G(d, p) method was used to calculate the geometry optimization of the different imprinting ratios, the action sites, the bonding situation, and the optimization of the cross-linking agents. The nature of the imprinting effect was also studied by the atoms in molecules theory. The theoretical results showed that melamine interacts with methacrylic acid by hydrogen bonding, and the melamine molecularly imprinted polymers with a molar ratio of 1:6 have the most hydrogen bonds and the most stable structure. Divinylbenzene is the best cross-linking agent for the melamine molecularly imprinted polymers. The melamine molecularly imprinted polymers were synthesized by precipitation polymerization. The results showed that the maximum adsorption capacity for molecularly imprinted polymers towards melamine is 19.84 mg/g, and the adsorption quantity of the polymers to melamine is obviously higher than that of cyromazine, cyanuric acid, and trithiocyanuric in milk. This study could provide theoretical and experimental references for the screening of the imprinting ratio and the cross-linking agent for the given template and monomer system.

  1. Fundamental Energetic Materials Initiative: Combat Safe Energetic Ingredients Based on Molecular Design and Crystal Morphology

    Science.gov (United States)

    2011-11-30

    loading conditions at the molecular and crystal levels. Replace one of the six bulk commodity chemicals currently used in all military propellant and...tetrazocine (HMX), nitroglycerin (NG), nitrocellulose (NC)) is the only way to achieve IM compliance. B. M. Rice and J. J. Hare, “A Quantum Mechanical

  2. New mimetic peptides inhibitors of ABeta aggregation. Molecular guidance for rational drug design

    NARCIS (Netherlands)

    Barrera Guisasola, E.E.; Andujar, S.; Hubin, E.; Broersen, K.; Kraan, Y.M.; Mendez, L.; Delpiccolo, C.M.L.; Masman, M.F.; Rodriguez, A.M.; Enriz, R.D.

    2015-01-01

    A new series of mimetic peptides possessing a significant Aβ aggregation modulating effect was reported here. These compounds were obtained based on a molecular modelling study which allowed us to perform a structural-based virtual selection. Monitoring Aβ aggregation by thioflavin T fluorescence an

  3. New mimetic peptides inhibitors of Aβ aggregation. Molecular guidance for rational drug design

    NARCIS (Netherlands)

    Barrera Guisasola, E.E.; Andujar, S.; Hubin, E.; Broersen, K.; Kraan, Y.M.; Mendez, L.; Delpiccolo, C.M.L.; Masman, M.F.; Rodriguez, A.M.; Enriz, R.D.

    2015-01-01

    A new series of mimetic peptides possessing a significant Aβ aggregation modulating effect was reported here. These compounds were obtained based on a molecular modelling study which allowed us to perform a structural-based virtual selection. Monitoring Aβ aggregation by thioflavin T fluorescence an

  4. Molecular dynamics simulations in rational protein design : Stabilisation of fusarium solani pisi cutinase against anionic surfactants

    NARCIS (Netherlands)

    Creveld, Lucia Deborah

    2001-01-01

    Cutinases are enxymes with a molecular mass of 22-25 kDa that supposedly degrade ester bonds of the cutin polymer in the plant cell wall. They are serine esterases, also able to hydrolyse a wide variety of synthetic esters and triacylglycerols. As cutinase is an efficient catalyst both in solution a

  5. Dissociative electron attachment studies on acetone

    Energy Technology Data Exchange (ETDEWEB)

    Prabhudesai, Vaibhav S., E-mail: vaibhav@tifr.res.in; Tadsare, Vishvesh; Ghosh, Sanat; Gope, Krishnendu; Davis, Daly; Krishnakumar, E. [Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005 (India)

    2014-10-28

    Dissociative electron attachment (DEA) to acetone is studied in terms of the absolute cross section for various fragment channels in the electron energy range of 0–20 eV. H{sup −} is found to be the most dominant fragment followed by O{sup −} and OH{sup −} with only one resonance peak between 8 and 9 eV. The DEA dynamics is studied by measuring the angular distribution and kinetic energy distribution of fragment anions using Velocity Slice Imaging technique. The kinetic energy and angular distribution of H{sup −} and O{sup −} fragments suggest a many body break-up for the lone resonance observed. The ab initio calculations show that electron is captured in the multi-centered anti-bonding molecular orbital which would lead to a many body break-up of the resonance.

  6. Design of optimal laser pulses to control molecular rovibrational excitation in a heteronuclear diatomic molecule

    Indian Academy of Sciences (India)

    Sitansh Sharma; Gabriel G Balint-Kurti; Harjinder Singh

    2012-01-01

    Optimal control theory in combination with time-dependent quantum dynamics is employed to design laser pulses which can perform selective vibrational and rotational excitations in a heteronuclear diatomic system. We have applied the conjugate gradient method for the constrained optimization of a suitably designed functional incorporating the desired objectives and constraints. Laser pulses designed for several excitation processes of the molecule were able to achieve predefined dynamical goals with almost 100% yield.

  7. Structure-based design and synthesis of small molecular inhibitors disturbing the interaction of MLL1-WDR5.

    Science.gov (United States)

    Li, Dong-Dong; Chen, Wei-Lin; Xu, Xiao-Li; Jiang, Fen; Wang, Lei; Xie, Yi-Yue; Zhang, Xiao-Jin; Guo, Xiao-Ke; You, Qi-Dong; Sun, Hao-Peng

    2016-08-01

    MLL1 complex catalyzes the methylation of H3K4, and plays important roles in the development of acute leukemia harboring MLL fusion proteins. Targeting MLL1-WDR5 protein-protein interaction (PPI) to inhibit the activity of histone methyltransferase of MLL1 complex is a novel strategy for treating of acute leukemia. WDR5-47 (IC50 = 0.3 μM) was defined as a potent small molecule to disturb the interaction of MLL1-WDR5. Here, we described structure-based design and synthesis of small molecular inhibitors to block MLL1-WDR5 PPI. Especially, compound 23 (IC50 = 104 nM) was the most potent small molecular, and about 3-times more potent than WDR5-47. We also discussed the SAR of these series of compounds with docking study, which may stimulate more potent compounds.

  8. Design of efficient molecular organic light-emitting diodes by a high-throughput virtual screening and experimental approach

    Science.gov (United States)

    Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D.; Duvenaud, David; MacLaurin, Dougal; Blood-Forsythe, Martin A.; Chae, Hyun Sik; Einzinger, Markus; Ha, Dong-Gwang; Wu, Tony; Markopoulos, Georgios; Jeon, Soonok; Kang, Hosuk; Miyazaki, Hiroshi; Numata, Masaki; Kim, Sunghan; Huang, Wenliang; Hong, Seong Ik; Baldo, Marc; Adams, Ryan P.; Aspuru-Guzik, Alán

    2016-10-01

    Virtual screening is becoming a ground-breaking tool for molecular discovery due to the exponential growth of available computer time and constant improvement of simulation and machine learning techniques. We report an integrated organic functional material design process that incorporates theoretical insight, quantum chemistry, cheminformatics, machine learning, industrial expertise, organic synthesis, molecular characterization, device fabrication and optoelectronic testing. After exploring a search space of 1.6 million molecules and screening over 400,000 of them using time-dependent density functional theory, we identified thousands of promising novel organic light-emitting diode molecules across the visible spectrum. Our team collaboratively selected the best candidates from this set. The experimentally determined external quantum efficiencies for these synthesized candidates were as large as 22%.

  9. Design, synthesis and decoration of molecular scaffolds for exploitation in the production of alkaloid-like libraries.

    Science.gov (United States)

    Craven, Philip; Aimon, Anthony; Dow, Mark; Fleury-Bregeot, Nicolas; Guilleux, Rachel; Morgentin, Remy; Roche, Didier; Kalliokoski, Tuomo; Foster, Richard; Marsden, Stephen P; Nelson, Adam

    2015-06-01

    The design, synthesis and decoration of six small molecule libraries is described. Each library was inspired by structures embedded in the framework of specific alkaloid natural products. The development of optimised syntheses of the required molecular scaffolds is described, in which reactions including Pd-catalysed aminoarylation and diplolar cycloadditions have been exploited as key steps. The synthesis of selected exemplar screening compounds is also described. In five cases, libraries were subsequently nominated for production on the basis of the scope and limitations of the validation work, as well as predicted molecular properties. In total, the research has led to the successful synthesis of >2500 novel alkaloid-like compounds for addition to the screening collection (the Joint European Compound Library, JECL) of the European Lead Factory.

  10. Design considerations and computer modeling related to the development of molecular scaffolds and peptide mimetics for combinatorial chemistry.

    Science.gov (United States)

    Hruby, V J; Shenderovich, M; Lam, K S; Lebl, M

    1996-10-01

    A critical issue in drug discovery utilizing combinatorial chemistry as part of the discovery process is the choice of scaffolds to be used for a proper presentation, in a three-dimensional space, of the critical elements of structure necessary for molecular recognition (binding) and information transfer (agonist/ antagonist). In the case of polypeptide ligands, considerations related to the properties of various backbone structures (alpha-helix, beta-sheets, etc.; phi, psi space) and those related to three-dimensional presentation of side-chain moieties (topography; chi (chi) space) must be addressed, although they often present quite different elements in the molecular recognition puzzle. We have addressed aspects of this problem by examining the three-dimensional structures of chemically different scaffolds at various distances from the scaffold to evaluate their putative diversity. We find that chemically diverse scaffolds can readily become topographically similar. We suggest a topographical approach involving design in chi space to deal with these problems.

  11. Molecular self-assembly: Design, synthesis, and characterization of peptidic materials for bio- and nano-technologies

    Science.gov (United States)

    Lamm, Matthew S.

    The research presented in this dissertation focuses on the design, synthesis, and characterization of amphiphilic peptides capable of self-assembling into beta-sheet fibrils under specific aqueous solution conditions. The peptide design consists of two beta-sheet forming strands of alternating valine and lysine residues, flanking a central tetrapeptide sequence that contains a diproline. Depending on the chirality of the prolines the peptide can assume either an intramolecularly folded or an extended conformation in the self-assembled state. For the peptide where intramolecular folding is designed against, the self-assembled nanostructure was found to exhibit a unique, nontwisted laminated morphology. Experimental techniques including transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, Fourier transform infra-red spectroscopy and x-ray diffraction were employed to characterize the self-assembled structure and kinetics. With the understanding of the self-assembly process gained from these first peptides, other peptide sequences were rationally designed to assemble with a desired nanostructure. For example, the effect of peptide strand length in conserving the laminated morphology and controlling the fibril height was investigated. In addition, other peptides were designed so as to affect the self-assembled nanostructure by enforcing a parallel versus anti-parallel beta-sheet or by disrupting the registry of laminating beta-sheet filaments. In some cases, the peptides assembled into structures predicted by the initial design while other peptides assembled into unexpected fibril morphologies. The major conclusions from the research on these peptides is that the diproline sequence plays an important role in disrupting the beta-strand twist thereby resulting in a nontwisted laminated morphology. However, when the flanking beta-strands become long enough, the effect of the diproline sequence becomes diminished and the fibrils do

  12. Solid state photochemistry. Subpanel A-2(a): Design of molecular precursors for electronic materials

    Energy Technology Data Exchange (ETDEWEB)

    Wells, R.L. [Duke Univ., Durham, NC (United States)

    1996-09-01

    Recent achievements of synthetic chemistry in the field of electronic materials are presented in three categories; viz, precursor design for improved processing, new chemistry for selective growth, and new growth techniques. This is followed by a discussion of challenges and opportunities in two general areas designated as composition and structure, and growth and processing.

  13. Computational design and multivariate optimization of an electrochemical metoprolol sensor based on molecular imprinting in combination with carbon nanotubes.

    Science.gov (United States)

    Nezhadali, Azizollah; Mojarrab, Maliheh

    2016-06-14

    This work describes the development of an electrochemical sensor based on a new molecularly imprinted polymer for detection of metoprolol (MTP) at ultra-trace level. The polypyrrole (PPy) was electrochemically synthesized on the tip of a pencil graphite electrode (PGE) which modified whit functionalized multi-walled carbon nanotubes (MWCNTs). The fabrication process of the sensor was characterized by cyclic voltammetry (CV) and the measurement process was carried out by differential pulse voltammetry (DPV). A computational approach was used to screening functional monomers and polymerization solvent for rational design of molecularly imprinted polymer (MIP). Based on computational results, pyrrole and water were selected as functional monomer and polymerization solvent, respectively. Several significant parameters controlling the performance of the MIP sensor were examined and optimized using multivariate optimization methods such as Plackett-Burman design (PBD) and central composite design (CCD). Under the selected optimal conditions, MIP sensor was showed a linear range from 0.06 to 490 μmol L(-1) MTP, a limit of detection of 2.88 nmol L(-1), a highly reproducible response (RSD 3.9%) and a good selectivity in the presence of structurally related molecules. Furthermore, the applicability of the method was successfully tested with determination of MTP in real samples (tablet, and serum).

  14. Design and evaluation of a molecular fingerprint involving the transformation of property descriptor values into a binary classification scheme.

    Science.gov (United States)

    Xue, Ling; Godden, Jeffrey W; Stahura, Florence L; Bajorath, Jürgen

    2003-01-01

    A new fingerprint design concept is introduced that transforms molecular property descriptors into two-state descriptors and thus permits binary encoding. This transformation is based on the calculation of statistical medians of descriptor distributions in large compound collections and alleviates the need for value range encoding of these descriptors. For binary encoded property descriptors, bit positions that are set off capture as much information as bit positions that are set on, different from conventional fingerprint representations. Accordingly, a variant of the Tanimoto coefficient has been defined for comparison of these fingerprints. Following our design idea, a prototypic fingerprint termed MP-MFP was implemented by combining 61 binary encoded property descriptors with 110 structural fragment-type descriptors. The performance of this fingerprint was evaluated in systematic similarity search calculations in a database containing 549 molecules belonging to 38 different activity classes and 5000 background molecules. In these calculations, MP-MFP correctly recognized approximately 34% of all similarity relationships, with only 0.04% false positives, and performed better than previous designs and MACCS keys. The results suggest that combinations of simplified two-state property descriptors have predictive value in the analysis of molecular similarity.

  15. Computational Design of a Family of Light-Driven Rotary Molecular Motors with Improved Quantum Efficiency.

    Science.gov (United States)

    Nikiforov, Alexander; Gamez, Jose A; Thiel, Walter; Filatov, Michael

    2016-01-07

    Two new light-driven molecular rotary motors based on the N-alkylated indanylidene benzopyrrole frameworks are proposed and studied using quantum chemical calculations and nonadiabatic molecular dynamics simulations. These new motors perform pure axial rotation, and the photochemical steps of the rotary cycle are dominated by the fast bond-length-alternation motion that enables ultrafast access to the S1/S0 intersection. The new motors are predicted to display a quantum efficiency higher than that of the currently available synthetic all-hydrocarbon motors. Remarkably, the quantum efficiency is not governed by the topography (peaked versus sloped) of the minimum-energy conical intersection, whereas the S1 decay time depends on the topography as well as on the energy of the intersection relative to the S1 minimum. It is the axial chirality (helicity), rather than the point chirality, that controls the sense of rotation of the motor.

  16. MOLECULAR DESIGN OF FUNCTIONAL POLYMERS BASED ON UNIQUE PROPERTIES OF POLYMER CHAINS

    Institute of Scientific and Technical Information of China (English)

    Mikiharu Kamachi

    2000-01-01

    The inclusion complex formation of α-CD, β-CD, and γ-CD with various water-soluble polymers has been investigated, and the relationship between the chain cross-sectional areas of the polymers and the diameters of the cavities of cyclodextrins (molecular recognition) was found. Polyrotaxanes and tubular polymers were prepared on the basis of molecular recognition. Several kinds of polymers having tetraphenylporphyrin (TPP) and paramagnetic metallotetraphenylporphyrin (AgTPP, CuTPP, VOTPP or ZnTPP) have been prepared by radical polymerization of the corresponding monomers. Visible spectra of these polymers show hypochromism in the Soret bands of TPP moieties as compared with those of monomers. Polymer effects were observed in the magnetic behavior and oxygen adsorption of paramagnetic metallotetraphenylporphyrin moieties. Moreover, polymer effects on photophysical and photochemical behavior were found in the amphiphilic polymers covalently tethered with small amounts of zinc(Ⅱ)-tetraphenylporphyrin (ZnTPP).

  17. Synthetic Molecular Machines for Active Self-Assembly: Prototype Algorithms, Designs, and Experimental Study

    Science.gov (United States)

    Dabby, Nadine L.

    Computer science and electrical engineering have been the great success story of the twentieth century. The neat modularity and mapping of a language onto circuits has led to robots on Mars, desktop computers and smartphones. But these devices are not yet able to do some of the things that life takes for granted: repair a scratch, reproduce, regenerate, or grow exponentially fast--all while remaining functional. This thesis explores and develops algorithms, molecular implementations, and theoretical proofs in the context of "active self-assembly" of molecular systems. The long-term vision of active self-assembly is the theoretical and physical implementation of materials that are composed of reconfigurable units with the programmability and adaptability of biology's numerous molecular machines. En route to this goal, we must first find a way to overcome the memory limitations of molecular systems, and to discover the limits of complexity that can be achieved with individual molecules. One of the main thrusts in molecular programming is to use computer science as a tool for figuring out what can be achieved. While molecular systems that are Turing-complete have been demonstrated [Winfree, 1996], these systems still cannot achieve some of the feats biology has achieved. One might think that because a system is Turing-complete, capable of computing "anything," that it can do any arbitrary task. But while it can simulate any digital computational problem, there are many behaviors that are not "computations" in a classical sense, and cannot be directly implemented. Examples include exponential growth and molecular motion relative to a surface. Passive self-assembly systems cannot implement these behaviors because (a) molecular motion relative to a surface requires a source of fuel that is external to the system, and (b) passive systems are too slow to assemble exponentially-fast-growing structures. We call these behaviors "energetically incomplete" programmable

  18. Rational Design of Antimalarial Drugs Using Molecular Modeling and Statistical Analysis.

    Science.gov (United States)

    Santos, Cleydson Breno Rodrigues dos; Lobato, Cleison Carvalho; Braga, Francinaldo Sarges; Costa, Josivan da Silva; Favacho, Hugo Alexandre Silva; Carvalho, Jose Carlos Tavares; Macedo, Williams Jorge da Cruz; Brasil, Davi Do Socorro Barros; Silva, Carlos Henrique Tomich de Paula da; Silva Hage-Melim, Lorane Izabel da

    2015-01-01

    Artemisinin is an antimalarial compound isolated from Artemisia annua L. that is effective against Plasmodium falciparum. This paper proposes the development of new antimalarial derivatives of artemisinin from a SAR study and statistical analysis by multiple linear regression (MLR). The HF/6-31G** method was used to determine the molecular properties of artemisinin and 10 derivatives with antimalarial action. MEP maps and molecular docking were used to study the interface between ligand and receptor (heme). The Pearson correlation was used to choose the most important properties interrelated to the antimalarial activity: Hydration Energy (HE), Energy of the Complex (Ecplex), bond length (FeO1), and maximum index of R/Electronegativity of Sanderson (RTe+). After the Pearson correlation, 72 MLR models were built between antimalarial activity and molecular properties; the statistical quality of the models was evaluated by means of correlation coefficient (r), squared correlation coefficient (r(2)), explained variance (adjusted R(2)), standard error of estimate (SEE), and variance ratio (F), and only four models showed predictive ability. The selected models were used to predict the antimalarial activity of ten new artemisinin derivatives (test set) with unknown activity, and only eight of these compounds were predicted to be more potent than artemisinin, and were therefore subjected to theoretical studies of pharmacokinetic and toxicological properties. The test set showed satisfactory results for six new artemisinin compounds which is a promising factor for future synthesis and biological assays.

  19. Design and First-principles Study of a Fullerene Molecular Device

    Institute of Scientific and Technical Information of China (English)

    OUYANG Fang-Ping; XU Hui

    2007-01-01

    @@ By using open-ended armchair (6, 6) single-wall carbon nanotubes as electrodes, we investigate the electron transport properties of an all-carbon molecular junction based on the C82 molecule. We find the most stable system among different isomers by performing structural optimization calculations of the C82 isomers and the C82 extended molecules. The calculated results show that the C82-C2 (3) isomer and the C82 extended molecule with C82-C2v isomer are most stable. For the all-carbon hybrid system consisting of C82-C2v extended molecules, it is shown that the Landauer conductance can be tuned over several orders of magnitude both by changing the distance between two electrodes and by changing the orientation of the C82 molecule or rotating one of the tubes around the symmetry axis of the system at a fixed distance. Also, we find the most stable distance between two electrodes from the total energy curve. This fact could make this all-carbon molecular system a possible candidate for a nanoelectronic switch. Moreover, we interpret the conductance mechanism for such a molecular device.

  20. ATTACHMENTS IN PROSTHODONTICS: DIFFERENT SYSTEMS OF CLASSIFICATION: A REVIEW

    Directory of Open Access Journals (Sweden)

    Khuthija Khanam

    2014-07-01

    Full Text Available Attachments are mechanical devices for the fixation and stabilisation of a dental prosthesis and include frictional, internal, intracoronal, extracoronal, key-key way, parallel, precision and slotted types. (Boucher 1976. Attachments are used as alternative to clasps in removable partial denture therapy for both aesthetic and functional purpose. Their application is not only limited to removable partial dentures, but has a broader usage in fixed bridges, overdentures, implant supported dentures as well. Hundreds of attachments are available commercially and significant differences exist between them. In this article, different systems of classification of attachments have been reviewed. They are categorised as precision and semi-precision depending on the method of manufacture, intracoronal and extra coronal depending on their location relative to the abutment tooth, rigid and resilient determined by the amount of movement allowed between the component parts, also as stud and bar attachments depending on the design. A classification system to more accurately evaluate differences among resilient attachments has also been described here.

  1. Design and synthesis of a fluorescent molecular imprinted polymer for use in an optical fibre-based cocaine sensor

    Science.gov (United States)

    Wren, Stephen P.; Piletsky, Sergey A.; Karim, Kal; Gascoine, Paul; Lacey, Richard; Sun, Tong; Grattan, Kenneth T. V.

    2014-05-01

    Previously, we have developed chemical sensors using fibre optic-based techniques for the detection of Cocaine, utilising molecularly imprinted polymers (MIPs) containing fluorescein moieties as the signalling groups. Here, we report the computational design of a fluorophore which was incorporated into a MIP for the generation of a novel sensor that offers improved sensitivity for Cocaine with a detection range of 1-100μM. High selectivity for Cocaine over a suite of known Cocaine interferants (25μM) was also demonstrated by measuring changes in the intensity of fluorescence signals received from the sensor.

  2. Guest-responsive structural adaptation of a rationally-designed molecular tweezer based on Tröger’s base

    Indian Academy of Sciences (India)

    Ishita Neogi; Alankriti Bajpai; Jarugu Narasimha Moorthy

    2014-09-01

    We have designed and synthesized a modified Tröger’s base TB in which the sterically-rigidified aryl rings that protrude into its groove were envisaged to preclude self-inclusion. From a limited preliminary experimentation, TB has been found to exhibit guest inclusion. The X-ray determined structures of the crystals of guest-free TB and its inclusion compounds with acetonitrile and -dichlorobenzene reveal remarkable adaptability of the TB core to undergo subtle structural changes in response to the guest that is included. The structural analyses demonstrate the fact that TB behaves like a molecular tweezer.

  3. Stud attachments for the mandibular implant-retained overdentures: Prosthetic complications. A literature review.

    Science.gov (United States)

    Daou, Elie E

    2013-04-01

    A plethora of attachment systems for mandibular two-implant overdentures is currently available often without evidence-based support. Technical aspects are now parameters considered when choosing the appropriate attachment. Despite the increasing use of the Locator attachments, studies regarding their properties remain scarce. Peer reviewed articles published in English up to 2011, were identified through a MEDLINE search (Pubmed and Elsevier) and a hand search of relevant textbooks and annual publications. Emphasis was made on the technical complications as well as the loss of retention related to the attachments in implant-retained overdentures, primarily the Locator attachment. The evaluation of the long-term outcome of implant overdentures and complications associated with different attachment systems may provide useful guidelines for the clinician in selecting the type of attachment system and overdenture design.

  4. Molecular drug targets and structure based drug design: A holistic approach

    OpenAIRE

    Singh, Shailza; Malik, Balwant Kumar; Sharma, Durlabh Kumar

    2006-01-01

    Access to the complete human genome sequence as well as to the complete sequences of pathogenic organisms provides information that can result in an avalanche of therapeutic targets. Structure-based design is one of the first techniques to be used in drug design. Structure based design refers specifically to finding and complementing the 3D structure (binding and/or active site) of a target molecule such as a receptor protein. The aim of this review is to give an outline of studies in the fie...

  5. Attachable rock bolters for roadheaders

    Energy Technology Data Exchange (ETDEWEB)

    Weibezahn, K. [Wirth Maschinen- und Bohrgeraete-Fabrik GmbH, Erkelenz (Germany); West, M. [Deilmann-Haniel Mining Systems GmbH (Germany)

    2004-07-01

    Roadheaders are used in mining and tunnelling in medium hard rock formations. The excavated space is made safe either by NATM-technology or a steel support system. The application of a rock bolting system up to now was restricted to formations that can cope with at least some support lag. A new system was developed in close cooperation between WIRTH Maschinen- und Bohrgeraetefabrik GmbH and deilmann-haniel mining systems gmbh that allows to carry out rock bolting with two drill rigs whicht are attached to the cutting boom of the roadheader even in front of the cutter head directly after cutting. Alternatively a robot may be attached to above named system that enables remotely controlled shot-creting close to the face.

  6. Molecular design of interfacial modifiers for polymer-inorganic hybrid solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jusfong; Shen, Tsung-Lung; Weng, Wei-Hsiang; Huang, Yu-Chen; Huang, Ching-I; Su, Wei-Fang; Ho, Kuo-Chuan [Institute of Polymer Science and Engineering, National Taiwan University, Taipei (China); Rwei, Syang-Peng [Institute of Organic and Polymeric Materials, National Taipei University of Technology, Taipei (China); Wang, Leeyih [Institute of Polymer Science and Engineering, National Taiwan University, Taipei (China); Center for Condensed Matter Sciences and Center for Emerging Material and Advanced Devices, National Taiwan University, Taipei (China)

    2012-02-15

    The heterojunction of poly(3-hexylthiophene) (P3HT) and TiO{sub 2} in hybrid solar cells is systematically engineered with four cyanoacrylic acid-containing conjugated molecules with various lowest unoccupied molecular orbital (LUMO) levels, WL-1 to WL-4, which are prepared by the formylation of thiophene derivatives in a Vilsmeier-Haack reaction, followed by treatment with cyanoacetic acid. The optical characteristics, redox properties, and intrinsic dipole moments of these interfacial modifiers (IMs) are examined using UV-vis spectrophotometry, cyclic voltammetry, and density functional theory calculations. Using cyanoacrylic acid as a terminal anchoring group in IMs increases the electron affinity in regions close to the titania surface and forms a molecular dipole that is orientated away from the TiO{sub 2} surface, enabling both open-circuit voltage (V{sub OC}) and short-circuit current density to be increased simultaneously. Photovoltaic measurements demonstrate that V{sub OC} increases with the dipole moment of IMs along the molecular backbone. Moreover, the external quantum efficiency (EQE) spectra display a bimodal distribution, revealing that both IMs and P3HT contribute to the photocurrent. The EQE at 570 nm is identified as characteristic of P3HT. More importantly, the LUMO of the IMs decisively determines the dissociation efficiency of P3HT excitons. The device based on P3HT/WL-4/TiO{sub 2} exhibits the highest power conversion efficiency of 2.87%. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. Adult attachment processes: individual and couple perspectives.

    Science.gov (United States)

    Bartholomew, K

    1997-09-01

    This paper overviews a new approach to understanding the range of difficulties experienced in close attachment relationships in adulthood. Drawing on the work of Bowlby, four prototypic adult attachment patterns are defined in terms of the intersection of two underlying dimensions, the positivity of the person's self-image and the positivity of the person's image of others (Bartholomew, 1990; Bartholomew & Horowitz, 1991). The distinct interpersonal difficulties associated with each attachment pattern are described. Findings are presented indicating that individual differences in attachment have implications for the quality of adults' romantic relationships, and that attachment theory may be helpful in understanding violent spousal relationships. Five current issues in the study of adult attachment are addressed: the stability of attachment patterns, the associations between attachment and general personality factors, the relative merits of categorical and prototype assessments of attachment, the identification of multiple attachments in adulthood, and the specificity of adult attachment patterns. It is suggested that the four-category model of adult attachment is especially sensitive to the range and complexity of attachment-related difficulties experienced in adulthood.

  8. Zoospores of Undaria pinnatifida: their efficiency to attach under different water velocities and conjugation behavior during attachment

    Institute of Scientific and Technical Information of China (English)

    PANG Shaojun; SHAN Tifeng

    2008-01-01

    In the invading course of Undaria pinnatifida,zoospore attachment in a dynamically changed subtidal water environment is crucial for the establishment of a potential population in alien waters.Among many abiotic factors that may interfere with the attachment process,water velocity is the most important one.In this investigation,the effect of water velocity on zoospore attachment of U.pinnatifida was investigated in an artificially designed system.It was found that freshly released zoospores that were transported by water flowing at 0 ~ 16 cm/s showed no difficulty in attaching the smooth surface.Zoospore attachment decreased at elevated water flowing rates.At 70 cm/s no spore attachment occurred.Spores that have settled on glass slide for up to 1 h could not be stripped away by flowing water at a rate of 129 cm/s,the same was true of the 20 d old filamentous gametophytes.It was found that more than 70% of free-swimming zoospores tended to settle down adjacent to the settled spores and formed conjugated clusters from two up to a few hundred cells in still culture.

  9. Emanuel Miller Lecture: Attachment Insecurity, Disinhibited Attachment, and Attachment Disorders--Where Do Research Findings Leave the Concepts?

    Science.gov (United States)

    Rutter, Michael; Kreppner, Jana; Sonuga-Barke, Edmund

    2009-01-01

    Background: Despite the evidence on anomalous attachment patterns, there has been a tendency to interpret most of these as reflecting differences in security/insecurity. Methods: Empirical research findings are reviewed in relation to attachment/insecurity as evident in both infancy and later childhood, disorganised attachment, inhibited…

  10. Magnetically Attached Multifunction Maintenance Rover

    Science.gov (United States)

    Bar-Cohen, Yoseph; Joffe, Benjamin

    2005-01-01

    A versatile mobile telerobot, denoted the magnetically attached multifunction maintenance rover (MAGMER), has been proposed for use in the inspection and maintenance of the surfaces of ships, tanks containing petrochemicals, and other large ferromagnetic structures. As its name suggests, this robot would utilize magnetic attraction to adhere to a structure. As it moved along the surface of the structure, the MAGMER would perform tasks that could include close-up visual inspection by use of video cameras, various sensors, and/or removal of paint by water-jet blasting, laser heating, or induction heating. The water-jet nozzles would be mounted coaxially within compressed-air-powered venturi nozzles that would collect the paint debris dislodged by the jets. The MAGMER would be deployed, powered, and controlled from a truck, to which it would be connected by hoses for water, compressed air, and collection of debris and by cables for electric power and communication (see Figure 1). The operation of the MAGMER on a typical large structure would necessitate the use of long cables and hoses, which can be heavy. To reduce the load of the hoses and cables on the MAGMER and thereby ensure its ability to adhere to vertical and overhanging surfaces, the hoses and cables would be paid out through telescopic booms that would be parts of a MAGMER support system. The MAGMER would move by use of four motorized, steerable wheels, each of which would be mounted in an assembly that would include permanent magnets and four pole pieces (see Figure 2). The wheels would protrude from between the pole pieces by only about 3 mm, so that the gap between the pole pieces and the ferromagnetic surface would be just large enough to permit motion along the surface but not so large as to reduce the magnetic attraction excessively. In addition to the wheel assemblies, the MAGMER would include magnetic adherence enhancement fixtures, which would comprise arrays of permanent magnets and pole pieces

  11. Design, synthesis, molecular docking studies and anti-HBV activity of phenylpropanoid derivatives.

    Science.gov (United States)

    Liu, Sheng; Li, Yubin; Wei, Wanxing; Wang, Kuiwu; Wang, Lisheng; Wang, Jianyi

    2016-05-01

    In this work, a series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated. Most of the synthesized derivatives showed effective anti-HBV activity. And compound 4d-3 showed the most effective anti-HBV activity, performing strong potent inhibitory not only on the secretion of HBsAg (IC50 = 58.28 μM, SI = 23.26) and HBeAg (IC50 = 97.21 μM, SI = 13.95), but also on the HBV DNA replication (IC50 = 42.28 μM, SI = 32.06). The structure-activity relationships (SARs) of the derivatives had been discussed, which were useful for developing phenylpropanoid derivatives as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site was carried out to explore the molecular interactions and a molecular target for activity and a modified assay method measuring the interaction between our derivatives and HBcAg was investigated, indicating that the HBV core protein might be their potential target for anti-HBV. This study identified a new class of potent non-nucleoside anti-HBV agents.

  12. Design, synthesis, α-glucosidase inhibitory activity, molecular docking and QSAR studies of benzimidazole derivatives

    Science.gov (United States)

    Dinparast, Leila; Valizadeh, Hassan; Bahadori, Mir Babak; Soltani, Somaieh; Asghari, Behvar; Rashidi, Mohammad-Reza

    2016-06-01

    In this study the green, one-pot, solvent-free and selective synthesis of benzimidazole derivatives is reported. The reactions were catalyzed by ZnO/MgO containing ZnO nanoparticles as a highly effective, non-toxic and environmentally friendly catalyst. The structure of synthesized benzimidazoles was characterized using spectroscopic technics (FT-IR, 1HNMR, 13CNMR). Synthesized compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 3c, 3e, 3l and 4n were potent inhibitors with IC50 values ranging from 60.7 to 168.4 μM. In silico studies were performed to explore the binding modes and interactions between enzyme and synthesized benzimidazoles. Developed linear QSAR model based on density and molecular weight could predict bioactivity of newly synthesized compounds well. Molecular docking studies revealed the availability of some hydrophobic interactions. In addition, the bioactivity of most potent compounds had good correlation with estimated free energy of binding (ΔGbinding) which was calculated according to docked best conformations.

  13. MaMiCo: Software design for parallel molecular-continuum flow simulations

    KAUST Repository

    Neumann, Philipp

    2015-11-19

    The macro-micro-coupling tool (MaMiCo) was developed to ease the development of and modularize molecular-continuum simulations, retaining sequential and parallel performance. We demonstrate the functionality and performance of MaMiCo by coupling the spatially adaptive Lattice Boltzmann framework waLBerla with four molecular dynamics (MD) codes: the light-weight Lennard-Jones-based implementation SimpleMD, the node-level optimized software ls1 mardyn, and the community codes ESPResSo and LAMMPS. We detail interface implementations to connect each solver with MaMiCo. The coupling for each waLBerla-MD setup is validated in three-dimensional channel flow simulations which are solved by means of a state-based coupling method. We provide sequential and strong scaling measurements for the four molecular-continuum simulations. The overhead of MaMiCo is found to come at 10%-20% of the total (MD) runtime. The measurements further show that scalability of the hybrid simulations is reached on up to 500 Intel SandyBridge, and more than 1000 AMD Bulldozer compute cores. Program summary: Program title: MaMiCo. Catalogue identifier: AEYW_v1_0. Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEYW_v1_0.html Program obtainable from: CPC Program Library, Queen\\'s University, Belfast, N. Ireland. Licensing provisions: BSD License. No. of lines in distributed program, including test data, etc.: 67905. No. of bytes in distributed program, including test data, etc.: 1757334. Distribution format: tar.gz. Programming language: C, C++II. Computer: Standard PCs, compute clusters. Operating system: Unix/Linux. RAM: Test cases consume ca. 30-50 MB. Classification: 7.7. External routines: Scons (http:www.scons.org), ESPResSo, LAMMPS, ls1 mardyn, waLBerla. Nature of problem: Coupled molecular-continuum simulation for multi-resolution fluid dynamics: parts of the domain are resolved by molecular dynamics whereas large parts are covered by a CFD solver, e.g. a lattice Boltzmann automaton

  14. Energy Decomposition Analysis Based on Absolutely Localized Molecular Orbitals for Large-Scale Density Functional Theory Calculations in Drug Design.

    Science.gov (United States)

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

    2016-07-12

    We report the development and implementation of an energy decomposition analysis (EDA) scheme in the ONETEP linear-scaling electronic structure package. Our approach is hybrid as it combines the localized molecular orbital EDA (Su, P.; Li, H. J. Chem. Phys., 2009, 131, 014102) and the absolutely localized molecular orbital EDA (Khaliullin, R. Z.; et al. J. Phys. Chem. A, 2007, 111, 8753-8765) to partition the intermolecular interaction energy into chemically distinct components (electrostatic, exchange, correlation, Pauli repulsion, polarization, and charge transfer). Limitations shared in EDA approaches such as the issue of basis set dependence in polarization and charge transfer are discussed, and a remedy to this problem is proposed that exploits the strictly localized property of the ONETEP orbitals. Our method is validated on a range of complexes with interactions relevant to drug design. We demonstrate the capabilities for large-scale calculations with our approach on complexes of thrombin with an inhibitor comprised of up to 4975 atoms. Given the capability of ONETEP for large-scale calculations, such as on entire proteins, we expect that our EDA scheme can be applied in a large range of biomolecular problems, especially in the context of drug design.

  15. In silico designing breast cancer peptide vaccine for binding to MHC class I and II: A molecular docking study.

    Science.gov (United States)

    Mahdavi, Manijeh; Moreau, Violaine

    2016-12-01

    Antigenic peptides or cancer peptide vaccines can be directly delivered to cancer patients to produce immunologic responses against cancer cells. Specifically, designed peptides can associate with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells activating anti-tumor effector mechanisms by triggering helper T cell (Th) or cytotoxic T cells (CTL). In general, high binding to MHCs approximately correlates with in vivo immunogenicity. Consequently, a molecular docking technique was run on a library of novel discontinuous peptides predicted by PEPOP from Human epidermal growth factor receptor 2 (HER2 ECD) subdomain III. This technique is expected to improve the prediction accuracy in order to identify the best MHC class I and II binder peptides. Molecular docking analysis through GOLD identified the peptide 1412 as the best MHC binder peptide to both MHC class I and II molecules used in the study. The GOLD results predicted HLA-DR4, HLA-DP2 and TCR as the most often targeted receptors by the peptide 1412. These findings, based on bioinformatics analyses, can be exploited in further experimental analyses in vaccine design and cancer therapy to find possible proper approaches providing beneficial effects.

  16. Molecularly designed lipid microdomains for solid dispersions using a polymer/inorganic carrier matrix produced by hot-melt extrusion.

    Science.gov (United States)

    Adler, Camille; Schönenberger, Monica; Teleki, Alexandra; Kuentz, Martin

    2016-02-29

    Amorphous solid dispersions have for many years been a focus in oral formulations, especially in combination with a hot-melt extrusion process. The present work targets a novel approach with a system based on a fatty acid, a polymer and an inorganic carrier. It was intended to adsorb the acidic lipid by specific molecular interactions onto the solid carrier to design disorder in the alkyl chains of the lipid. Such designed lipid microdomains (DLM) were created as a new microstructure to accommodate a compound in a solid dispersion. Vibrational spectroscopy, X-ray powder diffraction, atomic force microscopy as well as electron microscopic imaging were employed to study a system of stearic acid, hydroxypropylcellulose and aluminum magnesium silicate. β-carotene was used as a poorly water-soluble model substance that is difficult to formulate with conventional solid dispersion formulations. The results indicated that the targeted molecular excipient interactions indeed led to DLMs for specific compositions. The different methods provided complementary aspects and important insights into the created microstructure. The novel delivery system appeared to be especially promising for the formulation of oral compounds that exhibit both high crystal energy and lipophilicity.

  17. Engineered microtopographies and surface chemistries direct cell attachment and function

    Science.gov (United States)

    Magin, Chelsea Marie

    topographically modified surface (R2=0.82). Functionalized PEGDMA hydrogels significantly reduced attachment and attachment strength of Navicula and C. marina. These hydrogels also reduced attachment of zoospores of Ulva compared to PDMSe. Attachment of Ulva to microtopographies in PDMSe and PEGDMA-co-HEMA negatively correlated with ERIII*Re (R2 = 0.94 and R2 = 0.99, respectively). Incorporating a surface energy term into this equation created a correlation between the attachment densities of cells from two evolutionarily diverse groups on substrates of two surface chemistries with an equation that describes the various microtopographies and surface chemistries in terms of surface energy (R2 = 0.80). The current Attachment Model can now be used to design engineered antifouling surface microtopographies and chemistries that inhibit the attachment of organisms from three evoluntionarily diverse groups. Hydrogels based on PEGDMA were also chosen as a substratum material for mammalian cell culture. Capturing endothelial progenitor cells (EPCs) and inducing differentiation into the endothelial cell (EC) phenotype is the ideal way to re-endothelialize a small-diameter vascular graft. Substratum elasticity has been reported to direct stem cell differentiation into specific lineages. Functionalized PEGDMA hydrogels provided good compliance, high fidelity of topographic features and sites for surface modification with biomolecules. Fibronectin grafting and topography both increased EC attachment. This combination of adjustable elasticity, surface chemistry and topography has the potential to promote the capture and differentiation of EPCs into a confluent EC monolayer. Engineered microtopographies replicated in PDMSe directed elongation and alignment of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs) compared to smooth surfaces. Engineered cellular micro-environments were created with specific surface energies defined by chemistry

  18. Recent Design Development in Molecular Imaging for Breast Cancer Detection Using Nanometer CMOS Based Sensors.

    Science.gov (United States)

    Nguyen, Dung C; Ma, Dongsheng Brian; Roveda, Janet M W

    2012-01-01

    As one of the key clinical imaging methods, the computed X-ray tomography can be further improved using new nanometer CMOS sensors. This will enhance the current technique's ability in terms of cancer detection size, position, and detection accuracy on the anatomical structures. The current paper reviewed designs of SOI-based CMOS sensors and their architectural design in mammography systems. Based on the existing experimental results, using the SOI technology can provide a low-noise (SNR around 87.8 db) and high-gain (30 v/v) CMOS imager. It is also expected that, together with the fast data acquisition designs, the new type of imagers may play important roles in the near-future high-dimensional images in additional to today's 2D imagers.

  19. Attaching Chuck Keys to Machine Tools

    Science.gov (United States)

    Richardson, V.

    1984-01-01

    Chuck keys attached to portable machine tools by retracting lanyards. Lanyard held taut by recoil caddy attached to tool base. Chuck key available for use when needed and safely secured during operation of tool.

  20. Analysis strategies for longitudinal attachment loss data.

    Science.gov (United States)

    Beck, J D; Elter, J R

    2000-02-01

    The purpose of this invited review is to describe and discuss methods currently in use to quantify the progression of attachment loss in epidemiological studies of periodontal disease, and to make recommendations for specific analytic methods based upon the particular design of the study and structure of the data. The review concentrates on the definition of incident attachment loss (ALOSS) and its component parts; measurement issues including thresholds and regression to the mean; methods of accounting for longitudinal change, including changes in means, changes in proportions of affected sites, incidence density, the effect of tooth loss and reversals, and repeated events; statistical models of longitudinal change, including the incorporation of the time element, use of linear, logistic or Poisson regression or survival analysis, and statistical tests; site vs person level of analysis, including statistical adjustment for correlated data; the strengths and limitations of ALOSS data. Examples from the Piedmont 65+ Dental Study are used to illustrate specific concepts. We conclude that incidence density is the preferred methodology to use for periodontal studies with more than one period of follow-up and that the use of studies not employing methods for dealing with complex samples, correlated data, and repeated measures does not take advantage of our current understanding of the site- and person-level variables important in periodontal disease and may generate biased results.

  1. Molecular Design Breeding in Crops in China%中国作物分子设计育种

    Institute of Scientific and Technical Information of China (English)

    王建康; 李慧慧; 张学才; 尹长斌; 黎裕; 马有志; 李新海; 邱丽娟; 万建民

    2011-01-01

    分子设计育种通过多种技术的集成与整合,对育种程序中的诸多因素进行模拟、筛选和优化,提出最佳的符合育种目标的基因型以及实现目标基因型的亲本选配和后代选择策略,以提高作物育种中的预见性和育种效率,实现从传统的"经验育种"到定向、高效的"精确育种"的转化.分子设计育种主要包含以下3个步骤:(1)研究目标性状基因以及基因间的相互关系,即找基因(或生产品种的原材料),这一步骤包括构建遗传群体、筛选多态性标记、构建遗传连锁图谱、数量性状表型鉴定和遗传分析等内容;(2)根据不同生态环境条件下的育种目标设计目标基因型,即找目标(或设计品种原型),这一步骤利用已经鉴定出的各种重要育种性状的基因信息,包括基因在染色体上的位置、遗传效应、基因到性状的生化网络和表达途径、基因之间的互作、基因与遗传背景和环境之间的互作等,模拟预测各种可能基因型的表现型,从中选择符合特定育种目标的基因型;(3)选育目标基因型的途径分析,即找途径(或制定生产品种的育种方案).本文评述近几年来我国在遗传研究材料创新、重要性状遗传分析、育种模拟工具开发和应用、设计育种实践、分子设计育种技术体系建设等方面取得的重要进展,结合国内外研究现状对分子设计育种的未来进行展望,最后指出我国近期应加强育种预测方法和工具、基因和环境互作、遗传交配设计、作物功能基因组学、生物信息学方法和工具、设计育种技术体系和决策支持平台等领域的研究,同时重视人才培养和团队建设.%Molecular design breeding is a highly integrated system built on multiple scientific disciplines and technological areas.It allows the simulation and optimization of the breeding procedure before breeders’ field experiments.Thus the best target genotypes

  2. Forced vibration of a ball attached to a cable

    Directory of Open Access Journals (Sweden)

    Douglas Oliver

    2000-01-01

    Full Text Available This work describes an analytic solution to predict the forced oscillation of a suspended cable and an attached ball. The oscillations are driven by a sinusoidal movement at the fixed end of the cable. This problem may be used in the verification of numerical software which is commonly used to design systems with suspended cables.

  3. Preconception Motivation and Pregnancy Wantedness: Pathways to Toddler Attachment Security

    Science.gov (United States)

    Miller, Warren B.; Sable, Marjorie R.; Beckmeyer, Jonathon J.

    2009-01-01

    This research was designed to increase our understanding of how the motivational antecedents to childbearing and emotional responses to pregnancy affect the subsequent attachment bond of a toddler to his or her mother. Using a sample of 1,364 mothers and their newborns from the Study of Early Child Care, we tested a mother-child influence…

  4. Romantic Attachment and Relationship Functioning in Same-Sex Couples

    Science.gov (United States)

    Mohr, Jonathan J.; Selterman, Dylan; Fassinger, Ruth E.

    2013-01-01

    The present study was designed to investigate links between dimensions of romantic attachment and relationship functioning in a cross-sectional sample of people in same-sex relationships, with the goals of replicating basic findings from research on heterosexual couples and advancing understanding of unique issues faced by same-sex couples. The…

  5. Molecular design, self-assembly, and material properties of silk-like protein polymers

    NARCIS (Netherlands)

    Beun, L.H.

    2015-01-01

    Summary In this thesis we present the design and characterization of bio-inspired hybrid protein polymers. All polymers are composed of two distinct types of building blocks. The first type is a silk-inspired block that is pH-responsive and can fold and self-assemble into highly ordered structures.

  6. Design, synthesis and molecular docking studies of novel triazole antifungal compounds

    Institute of Scientific and Technical Information of China (English)

    Qiu Qin He; Ke Li; Yong Bing Cao; Huan Wen Dong; Li Hua Zhao; Chao Mei Liu; Chun Quan Sheng

    2007-01-01

    Based on the active site of Candida albicans lanosterol 14α-demethylase (CACYP51), novel triazole compounds structurally different from the current triazole drugs were designed and synthesized.In vitro antifungal activities showed that compounds 10,11,16 and 20 exhibited strong activities.In addition, compounds 10,11 and 16 also displayed certain activities against fluconazole-resistant fungi.

  7. Very-high-strength (60-GPa) carbon nanotube fiber design based on molecular dynamics simulations

    Science.gov (United States)

    Cornwell, Charles F.; Welch, Charles R.

    2011-05-01

    The mechanical properties of carbon nanotubes such as low density, high stiffness, and exceptional strength make them ideal candidates for reinforcement material in a wide range of high-performance composites. Molecular dynamics simulations are used to predict the tensile response of fibers composed of aligned carbon nanotubes with intermolecular bonds of interstitial carbon atoms. The effects of bond density and carbon nanotube length distribution on fiber strength and stiffness are investigated. The interstitial carbon bonds significantly increase load transfer between the carbon nanotubes over that obtained with van der Waals forces. The simulation results indicate that fibers with tensile strengths to 60 GPa could be produced by employing interstitial cross-link atoms. The elastic modulus of the fibers is also increased by the bonds.

  8. MATEO: a software package for the molecular design of energetic materials.

    Science.gov (United States)

    Mathieu, Didier

    2010-04-15

    To satisfy the need of energetic materials chemists for reliable and efficient predictive tools in order to select the most promising candidates for synthesis, a custom software package is developed. Making extensive use of publicly available software, it integrates a wide range of models and can be used for a variety of tasks, from the calculation of molecular properties to the prediction of the performance of heterogeneous materials, such as propellant compositions based on ammonium perchlorate/aluminium mixtures. The package is very easy to use through a graphical desktop environment. According to the material provided as input, suitable models and parameters are automatically selected. Therefore, chemists can apply advanced predictive models without having to learn how to use complex computer codes. To make the package more versatile, a command-line interface is also provided. It facilitates the assessment of various procedures by model developers.

  9. Photomobile polymer materials with crosslinked liquid-crystalline structures: molecular design, fabrication, and functions.

    Science.gov (United States)

    Ube, Toru; Ikeda, Tomiki

    2014-09-22

    Crosslinked liquid-crystalline polymer materials that macroscopically deform when irradiated with light have been extensively studied in the past decade because of their potential in various applications, such as microactuators and microfluidic devices. The basic motions of these materials are contraction-expansion and bending-unbending, which are observed mainly in polysiloxanes and polyacrylates that contain photochromic moieties. Other sophisticated motions such as twisting, oscillation, rotation, and translational motion have also been achieved. In recent years, efforts have been made to improve the photoresponsive and mechanical properties of this novel class of materials through the modification of molecular structures, development of new fabrication methods, and construction of composite structures. Herein, we review structures, functions, and working mechanisms of photomobile materials and recent advances in this field.

  10. Loneliness and Attachment Patterns in Young Adults.

    Science.gov (United States)

    Hecht, Diana Taylor; Baum, Steven K.

    1984-01-01

    Investigated the relationship between loneliness and patterns of attachment in 47 college students. Results revealed a moderate to strong relationship between feeling lonely and early disrupted attachment, consistent with the notion that underlying attachment disorders may affect psychological development and social behavior. (JAC)

  11. Attachment in rat pups, an experimental approach

    NARCIS (Netherlands)

    Gispen, W.H.; Sigling, H.; Engeland, H. van; Spruijt, B.M.

    1998-01-01

    John Bowlby's attachment theory states that attachment behavior has been strengthened throughout evolution as a consequence of its adaptive value. We investigated the presence of attachment-like behavior in rat pups, by offering a choice between the home nest and a same aged other nest. Rat pups sho

  12. Cesarean Births and Attachment Behaviors of Fathers.

    Science.gov (United States)

    1984-01-01

    Apgar scores are 7 or greater at both 1 and 5...status, indications for cesarean delivery, anesthesis, and infant’s gestational age, birth weight, and apgar scores . Prior to meeting the father, the...delivery and attachment score ; highest school grade completed and attachment score ; and age and child care experience of the father and attachment score

  13. Secondary Attachments and Adolescent Self Concept.

    Science.gov (United States)

    Adams-Price, Carolyn; Greene, A. L.

    1990-01-01

    In a study examining attachments to celebrity figures, 79 male and female fifth, eighth, and eleventh graders and college sophomores described themselves and their favorite celebrities. It was found that such attachments are equally important to males and females, and that gender and age affect the nature of the attachment. (DM)

  14. Easy Attachment Of Panels To A Truss

    Science.gov (United States)

    Thomson, Mark; Gralewski, Mark

    1992-01-01

    Conceptual antenna dish, solar collector, or similar structure consists of hexagonal panels supported by truss erected in field. Truss built in increments to maintain access to panel-attachment nodes. Each panel brought toward truss at angle and attached to two nodes. Panel rotated into attachment at third node.

  15. Reactive Attachment Disorder: Recommendations for School Counselors.

    Science.gov (United States)

    Hayes, Susanna H.

    1997-01-01

    Using a case study, explores a unique counseling relationship. Examines how the quality of parent-child attachment and care of a child during the formative preschool years affects interpersonal relationship skills and school adjustment. Discusses reactive attachment disorders, the pervasiveness of attachment disorders, and recommendations for…

  16. Attachment in Middle Childhood: Progress and Prospects

    Science.gov (United States)

    Bosmans, Guy; Kerns, Kathryn A.

    2015-01-01

    Contrary to the substantial amount of research on infant, preschool, adolescent, and adult attachment, middle childhood has long been neglected by the international attachment research community. In the past two decades, however, there has been a steep increase in research focusing on middle childhood attachment. This article provides an overview…

  17. 21 CFR 872.3165 - Precision attachment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Precision attachment. 872.3165 Section 872.3165...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3165 Precision attachment. (a) Identification. A precision attachment or preformed bar is a device made of austenitic alloys or alloys containing 75...

  18. Molecular Design of Nanofiltration Membranes for the Recovery of Phosphorus from Sewage Sludge

    KAUST Repository

    Thong, Zhiwei

    2016-08-24

    With the rapid depletion of mineral phosphorus, the recovery of phosphorus from sewage sludge becomes increasingly important. However, the presence of various contaminants such as heavy metals in sewage sludge complicates the issue. One must separate phosphorus from the heavy metals in order to produce fertilizers of high quality. Among various available methods, nanofiltration (NF) has been demonstrated to be a feasible and promising option when the sewage sludge undergoes acidic dissolution and the operating pH is around 2. Because the performance of commercially available thin film composite (TFC) NF membranes reported thus far has great room for improvement, the development of highly permeable positively charged NF membranes is recommended. To this aim, a NF membrane that is desirable for phosphorus recovery was fabricated via interfacial polymerization of polyethylenimine (PEI) and trimesoyl chloride (TMC) on a porous poly(ether sulfone) (PES) membrane substrate. Through an optimization of the interfacial polymerization process, which involves varying the molecular weight of PEI and the concentration of TMC, the resultant membrane displays a low molecular weight cutoff (MWCO) of 170 Da with a reasonably high pure water permeability (A) of 6.4 LMH/bar. The newly developed NF membrane can effectively reject a wide variety of heavy metal ions such as Cu, Zn, Pb and Ni (>93%) while demonstrating a low phosphorus rejection of 19.6% at 10 bar using a feed solution of pH 2. Thus, up to 90% of the feed phosphorus may be recovered using this newly developed NF membrane at a permeate recovery of 90%. This is a highly competitive value for the recovery of phosphorus. © 2016 American Chemical Society.

  19. Molecular Design, Expression and Evaluation of PASylated Human Recombinant Erythropoietin with Enhanced Functional Properties.

    Science.gov (United States)

    Hedayati, Mohammad Hossein; Norouzian, Dariush; Aminian, Mahdi; Teimourian, Shahram; Ahangari Cohan, Reza; Sardari, Soroush; Khorramizadeh, M Reza

    2017-02-01

    Erythropoietin (EPO) is the principal hormone which, has somewhat short half-life involved in the differentiation and regulation of circulating red blood cells. The present study was carried out to evaluate the capability of a polyethylene glycol mimetic technology as a biological alternative to improve pharmaceutical properties of human recombinant EPO. In silico models of EPO fused to 200 amino acids of proline, alanine, and serine (PAS) were initially generated and assessed by molecular dynamic (MD) simulation. The fluctuations of the modeled structure reached a plateau after 6000 ps of MD simulation. The Phi and psi analysis showed >99.2% of residues were located in the allowed regions. An expression vector consisting of EPO cDNA tagged to PAS coding sequences was synthesized and expressed in CHO-K1 Cells. The produced PASylated molecule was purified and characterized by standard analytical methods. The molecular weight of fusion protein was expanded to 70 kDa using sodium dodecyl sulfate polyacrylamide gel electrophoresis method. Analytical size exclusion chromatography revealed an approximately sevenfold increase in apparent size of produced protein. Although the in vitro potency of the fusion protein was significantly reduced (1.26 ± 0.05 vs. 0.24 ± 0.03 ng/ml) but, the in vivo activity was considerably increased up to 1.58 × 10(5) IU/ml in normocythemic mice assay. Pharmacokinetic animal studies revealed strongly 15.6-fold plasma half-life extension for the PASylated EPO (83.16 ± 13.28 h) in comparison to epoetin α (8.5 ± 2.4 h) and darbepoetin α (25.3 ± 2.2h).

  20. Reactive attachment disorder--a theoretical model beyond attachment.

    Science.gov (United States)

    Minnis, Helen; Marwick, Helen; Arthur, Julie; McLaughlin, Alexis

    2006-09-01

    Despite its importance in public health, reactive attachment disorder (RAD) is an under-researched and little used clinical category. Abnormalities of social relatedness have long been documented in children who have been abused, neglected or institutionalised, but there have been more recent efforts to define these behaviours within the psychiatric nosology. There has been an implicit assumption that the central deficit in RAD is in the attachment system, but this has caused controversy and may have blocked research. We propose that RAD is better construed within the framework of intersubjectivity, which has a central role in the development of core brain and social functions and may also have had an important role in the evolution of a key human characteristic-complex social functioning. This broader framework may potentially explain apparently diverse symptoms such as indiscriminate friendliness and negative or unpredictable reunion responses. Finally, we suggest that a change of name may be useful in progressing the field, but accept that this may be difficult until there is better agreement in the clinical and scientific communities about the core features and aetiology of this disorder.

  1. From Molecular to Macroscopic via the Rational Design of a Self-Assembled 3D DNA Crystal

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, J.; Birktoft, J; Yi, C; Tong, W; Ruojie, S; Constantinou, P; Ginell, S; Chenge, M; Seeman, N

    2009-01-01

    We live in a macroscopic three-dimensional (3D) world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires a bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter1. The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: a motif that has a robust 3D structure, dominant affinity interactions between parts of the motif when it self-associates, and predictable structures for these affinity interactions. Fulfilling these three criteria to produce a 3D periodic system is not easy, but should readily be achieved with well-structured branched DNA motifs tailed by sticky ends2. Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so3; the helically repeating nature of DNA facilitates the construction of a periodic array. It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter. Here we report the crystal structure at 4?Angstroms resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle4. The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.

  2. Molecular Design, Synthesis, and Evaluation of SNIPER(ER) That Induces Proteasomal Degradation of ERα.

    Science.gov (United States)

    Okuhira, Keiichiro; Demizu, Yosuke; Hattori, Takayuki; Ohoka, Nobumichi; Shibata, Norihito; Kurihara, Masaaki; Naito, Mikihiko

    2016-01-01

    Manipulation of protein stability using small molecules has a great potential for both basic research and clinical therapy. Based on our protein knockdown technology, we recently developed a novel small molecule SNIPER(ER) that targets the estrogen receptor alpha (ERα) for degradation via the ubiquitin-proteasome system. This chapter describes the design and synthesis of SNIPER(ER) compounds, and methods for the evaluation of their activity in cellular system.

  3. Molecular Evolution of Human PON to Design Enhanced Catalytic Efficiency for Hydrolysis of Nerve Agents

    Science.gov (United States)

    2011-06-01

    biomolecules that can intercept both existing and emerging organo - phosphate-based chemical warfare nerve agents (CWNA). All 5th year milestones have been met...w e have demonstrated the potential of direct ed evolution, combining random and designed mutations based on 3D struct ures, to generate m utants of...I., Harel, M., Rosenberry, T.L. & Sussman, J.L. (2010). “Acetylcholinesterase: From 3D structure to function ” Chem Biol Interact, 187, 10-22

  4. RNAiFOLD: a constraint programming algorithm for RNA inverse folding and molecular design.

    Science.gov (United States)

    Garcia-Martin, Juan Antonio; Clote, Peter; Dotu, Ivan

    2013-04-01

    Synthetic biology is a rapidly emerging discipline with long-term ramifications that range from single-molecule detection within cells to the creation of synthetic genomes and novel life forms. Truly phenomenal results have been obtained by pioneering groups--for instance, the combinatorial synthesis of genetic networks, genome synthesis using BioBricks, and hybridization chain reaction (HCR), in which stable DNA monomers assemble only upon exposure to a target DNA fragment, biomolecular self-assembly pathways, etc. Such work strongly suggests that nanotechnology and synthetic biology together seem poised to constitute the most transformative development of the 21st century. In this paper, we present a Constraint Programming (CP) approach to solve the RNA inverse folding problem. Given a target RNA secondary structure, we determine an RNA sequence which folds into the target structure; i.e. whose minimum free energy structure is the target structure. Our approach represents a step forward in RNA design--we produce the first complete RNA inverse folding approach which allows for the specification of a wide range of design constraints. We also introduce a Large Neighborhood Search approach which allows us to tackle larger instances at the cost of losing completeness, while retaining the advantages of meeting design constraints (motif, GC-content, etc.). Results demonstrate that our software, RNAiFold, performs as well or better than all state-of-the-art approaches; nevertheless, our approach is unique in terms of completeness, flexibility, and the support of various design constraints. The algorithms presented in this paper are publicly available via the interactive webserver http://bioinformatics.bc.edu/clotelab/RNAiFold; additionally, the source code can be downloaded from that site.

  5. Shape based virtual screening and molecular docking towards designing novel pancreatic lipase inhibitors

    OpenAIRE

    Veeramachaneni, Ganesh Kumar; Raj, K Kranthi; Chalasani,Leela Madhuri; Annamraju, Sai Krishna; Bondili JS; Talluri, Venkateswara Rao

    2015-01-01

    Increase in obesity rates and obesity associated health issues became one of the greatest health concerns in the present world population. With alarming increase in obese percentage there is a need to design new drugs related to the obesity targets. Among the various targets linked to obesity, pancreatic lipase was one of the promising targets for obesity treatment. Using the in silico methods like structure based virtual screening, QikProp, docking studies and binding energy calculations thr...

  6. Reliability Testing the Die-Attach of CPV Cell Assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Bosco, N.; Sweet, C.; Kurtz, S.

    2011-02-01

    Results and progress are reported for a course of work to establish an efficient reliability test for the die-attach of CPV cell assemblies. Test vehicle design consists of a ~1 cm2 multijunction cell attached to a substrate via several processes. A thermal cycling sequence is developed in a test-to-failure protocol. Methods of detecting a failed or failing joint are prerequisite for this work; therefore both in-situ and non-destructive methods, including infrared imaging techniques, are being explored as a method to quickly detect non-ideal or failing bonds.

  7. Plant cell walls throughout evolution: towards a molecular understanding of their design principles

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Purbasha; Bosneaga, Elena; Auer, Manfred

    2009-02-16

    Throughout their life, plants typically remain in one location utilizing sunlight for the synthesis of carbohydrates, which serve as their sole source of energy as well as building blocks of a protective extracellular matrix, called the cell wall. During the course of evolution, plants have repeatedly adapted to their respective niche,which is reflected in the changes of their body plan and the specific design of cell walls. Cell walls not only changed throughout evolution but also are constantly remodelled and reconstructed during the development of an individual plant, and in response to environmental stress or pathogen attacks. Carbohydrate-rich cell walls display complex designs, which together with the presence of phenolic polymers constitutes a barrier for microbes, fungi, and animals. Throughout evolution microbes have co-evolved strategies for efficient breakdown of cell walls. Our current understanding of cell walls and their evolutionary changes are limited as our knowledge is mainly derived from biochemical and genetic studies, complemented by a few targeted yet very informative imaging studies. Comprehensive plant cell wall models will aid in the re-design of plant cell walls for the purpose of commercially viable lignocellulosic biofuel production as well as for the timber, textile, and paper industries. Such knowledge will also be of great interest in the context of agriculture and to plant biologists in general. It is expected that detailed plant cell wall models will require integrated correlative multimodal, multiscale imaging and modelling approaches, which are currently underway.

  8. The Turkish version of Maternal Attachment Inventory

    Directory of Open Access Journals (Sweden)

    Oya Kavlak

    2009-01-01

    Full Text Available Objective: The research has been designed as methodological with purpose of the validity and the reliability of the Turkish language version of Maternal Attachment Inventory on mothers within one and four months postpartum. Method: This study was carried out with mothers registered at 19 Health Clinics and three Maternal-Child Health and Family Planning Clinics in which connected to Bornova Health Presidency in Izmir. The sample of research has been composed three clinics in which determined with the purposive sampling technique. First stage, the research was studied on 165 mothers when their babies were approximately 30-40 days old in these registered clinics.At the second stage of research has been interviewed again with 78 mothers when their babies were approximately 90-105 days old.Results: It is determined that experts consensuses about content of items as a result of analysis (Kendall’s W=0.274, p=0.001

  9. Handcrafting Attachment: A User-Centered Approach

    Directory of Open Access Journals (Sweden)

    George S. Lowry

    2011-04-01

    Full Text Available Management, above all, is the controlling element responsible for coordinating the three basic business functions; production, marketing, and finance.  Mechanisms exist to facilitate the finance function with influence coming from outside regulatory bodies such as the AICPA, IIA, SEC, and other regulators.  Integrating the finance function into organizations, then, becomes somewhat generic (although some would argue this point.  Coordinating the functions of marketing and production is a much more difficult endeavor because it lacks the standardization seen in finance.  This paper suggests employing a more user-focused approach as a means to improving the overall quality of products, and eventually, the success of the organization.  Specifically, this paper explores the role of the human brain in the calculus of choice, discusses the role of consumer involvement as it leads to product attachment, and offers suggestions for employing contextual research to improve product design and quality.

  10. Giant molecular clouds in the non-grand design spiral galaxy NGC 6946

    CERN Document Server

    Rebolledo, David; Leroy, Adam; Koda, Jin; Meyer, Jennifer Donovan

    2012-01-01

    We present high spatial resolution observations of Giant Molecular Clouds (GMCs) in the eastern part of the nearby spiral galaxy NGC 6946 obtained with the Combined Array for Research in Millimeter-wave Astronomy (CARMA). We have observed 12CO(1-0), 12CO(2-1) and 13CO(1-0), achieving spatial resolutions of 5.4" x 5.0", 2.5" x 2.0" and 5.6" x 5.4" respectively over a region of 6 x 6 kpc. This region extends from 1.5 kpc to 8 kpc galactocentric radius, thus avoiding the intense star formation in the central kpc. We have recovered short-spacing u-v components by using single dish observations from the Nobeyama 45m and IRAM 30m telescopes. Using the automated CPROPS algorithm we identified 44 CO cloud complexes in the 12CO(1-0) map and 64 GMCs in the 12CO(2-1) maps. The sizes, line widths, and luminosities of the GMCs are similar to values found in other extragalactic studies. We have classified the clouds into on-arm and inter-arm clouds based on the stellar mass density traced by the 3.6 um map. On-arm clouds p...

  11. Custom-tailored adsorbers: A molecular dynamics study on optimal design of ion exchange chromatography material.

    Science.gov (United States)

    Lang, Katharina M H; Kittelmann, Jörg; Pilgram, Florian; Osberghaus, Anna; Hubbuch, Jürgen

    2015-09-25

    The performance of functionalized materials, e.g., ion exchange resins, depends on multiple resin characteristics, such as type of ligand, ligand density, the pore accessibility for a molecule, and backbone characteristics. Therefore, the screening and identification process for optimal resin characteristics for separation is very time and material consuming. Previous studies on the influence of resin characteristics have focused on an experimental approach and to a lesser extent on the mechanistic understanding of the adsorption mechanism. In this in silico study, a previously developed molecular dynamics (MD) tool is used, which simulates any given biomolecule on resins with varying ligand densities. We describe a set of simulations and experiments with four proteins and six resins varying in ligand density, and show that simulations and experiments correlate well in a wide range of ligand density. With this new approach simulations can be used as pre-experimental screening for optimal adsorber characteristics, reducing the actual number of screening experiments, which results in a faster and more knowledge-based development of custom-tailored adsorbers.

  12. In Silico Design of Human IMPDH Inhibitors Using Pharmacophore Mapping and Molecular Docking Approaches

    Directory of Open Access Journals (Sweden)

    Rui-Juan Li

    2015-01-01

    Full Text Available Inosine 5′-monophosphate dehydrogenase (IMPDH is one of the crucial enzymes in the de novo biosynthesis of guanosine nucleotides. It has served as an attractive target in immunosuppressive, anticancer, antiviral, and antiparasitic therapeutic strategies. In this study, pharmacophore mapping and molecular docking approaches were employed to discover novel Homo sapiens IMPDH (hIMPDH inhibitors. The Güner-Henry (GH scoring method was used to evaluate the quality of generated pharmacophore hypotheses. One of the generated pharmacophore hypotheses was found to possess a GH score of 0.67. Ten potential compounds were selected from the ZINC database using a pharmacophore mapping approach and docked into the IMPDH active site. We find two hits (i.e., ZINC02090792 and ZINC00048033 that match well the optimal pharmacophore features used in this investigation, and it is found that they form interactions with key residues of IMPDH. We propose that these two hits are lead compounds for the development of novel hIMPDH inhibitors.

  13. Cobaltoporphyrin-Catalyzed CO 2 /Epoxide Copolymerization: Selectivity Control by Molecular Design

    KAUST Repository

    Anderson, Carly E.

    2012-09-11

    A series of cobalt(III) chloride porphyrin complexes of the general formula 5,10,15,20-tetra(p-alkoxy)phenylporphyrin cobalt chloride (4b-e) and the related 5,10,15,20-tetra(p-nitro)phenylporphyrin cobalt chloride (4f) are presented and their reactivity toward propylene oxide (PO)/CO 2 coupling/copolymerization is explored. While the nitro-substituted complex (4f), in conjunction with an onium salt, shows moderate activity toward cyclization, the 4b-e/onium systems show superior copolymerization activity in comparison to tetraphenylporphyrin Co(III) chloride (4a) with high selectivity and conversion to poly(propylene carbonate) (PPC). A comprehensive copolymerization behavior study of the alkoxy-substituted porphyrin complexes 4b-e in terms of reaction temperature and CO 2 pressure is presented. Complexes bearing longer alkoxy-substituents demonstrate the highest polymerization activity and molecular weights, however all substituted catalyst systems display a reduced tolerance to increased temperature with respect to PPC formation. Studies of the resulting polymer microstructures show excellent head-to-tail epoxide incorporation and near perfectly alternating poly(carbonate) character at lower polymerization temperatures. © 2012 American Chemical Society.

  14. Molecular docking studies with rabies virus glycoprotein to design viral therapeutics

    Directory of Open Access Journals (Sweden)

    Tomar N

    2010-01-01

    Full Text Available The genome of rabies virus encodes five proteins; the nucleoprotein, the phosphoprotein, the matrix protein, the glycoprotein, and the RNA-dependent RNA polymerase. Among these, the glycoprotein is the most important as it is the major contributor to pathogenicity and virus neutralizing antibody response. Keeping in mind that glycoprotein is the only protein exposed on the surface of virus and is thought to be responsible for the interaction with the cell membrane, it was attempted to target glycoprotein by a ligand polyethylene glycol 4000, which blocks its active site, as seen by molecular operating environment software, so that it may be possible to prevent the spread of virus into the host. The ligand polyethylene glycol 4000 was retrieved from Research Collaboratory for Structural Bioinformatics protein data bank by providing the glycoprotein sequence to the databank. In this study it was observed that the ligand was successfully docked on a major portion of antigenic site II of glycoprotein by mimicking the virus neutralizing antibodies. This knowledge may be important for the development of novel therapies for the treatment of rabies and other viral diseases in the future.

  15. De novo design of protein-protein interactions through modification of inter-molecular helix-helix interface residues.

    Science.gov (United States)

    Yagi, Sota; Akanuma, Satoshi; Yamagishi, Manami; Uchida, Tatsuya; Yamagishi, Akihiko

    2016-05-01

    For de novo design of protein-protein interactions (PPIs), information on the shape and chemical complementarity of their interfaces is generally required. Recent advances in computational PPI design have allowed for de novo design of protein complexes, and several successful examples have been reported. In addition, a simple and easy-to-use approach has also been reported that arranges leucines on a solvent-accessible region of an α-helix and places charged residues around the leucine patch to induce interactions between the two helical peptides. For this study, we adopted this approach to de novo design a new PPI between the helical bundle proteins sulerythrin and LARFH. A non-polar patch was created on an α-helix of LARFH around which arginine residues were introduced to retain its solubility. The strongest interaction found was for the LARFH variant cysLARFH-IV-3L3R and the sulerythrin mutant 6L6D (KD=0.16 μM). This artificial protein complex is maintained by hydrophobic and ionic interactions formed by the inter-molecular helical bundle structure. Therefore, by the simple and easy-to-use approach to create de novo interfaces on the α-helices, we successfully generated an artificial PPI. We also created a second LARFH variant with the non-polar patch surrounded by positively charged residues at each end. Upon mixing this LARFH variant with 6L6D, mesh-like fibrous nanostructures were observed by atomic force microscopy. Our method may, therefore, also be applicable to the de novo design of protein nanostructures.

  16. Molecular design of a highly selective and strong protein inhibitor against matrix metalloproteinase-2 (MMP-2).

    Science.gov (United States)

    Higashi, Shouichi; Hirose, Tomokazu; Takeuchi, Tomoka; Miyazaki, Kaoru

    2013-03-29

    Synthetic inhibitors of matrix metalloproteinases (MMPs), designed previously, as well as tissue inhibitors of metalloproteinases (TIMPs) lack enzyme selectivity, which has been a major obstacle for developing inhibitors into safe and effective MMP-targeted drugs. Here we designed a fusion protein named APP-IP-TIMP-2, in which the ten amino acid residue sequence of APP-derived MMP-2 selective inhibitory peptide (APP-IP) is added to the N terminus of TIMP-2. The APP-IP and TIMP-2 regions of the fusion protein are designed to interact with the active site and the hemopexin-like domain of MMP-2, respectively. The reactive site of the TIMP-2 region, which has broad specificity against MMPs, is blocked by the APP-IP adduct. The recombinant APP-IP-TIMP-2 showed strong inhibitory activity toward MMP-2 (Ki(app) = 0.68 pm), whereas its inhibitory activity toward MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, or MT1-MMP was six orders of magnitude or more weaker (IC50 > 1 μm). The fusion protein inhibited the activation of pro-MMP-2 in the concanavalin A-stimulated HT1080 cells, degradation of type IV collagen by the cells, and the migration of stimulated cells. Compared with the decapeptide APP-IP (t½ = 30 min), APP-IP-TIMP-2 (t½ ≫ 96 h) showed a much longer half-life in cultured tumor cells. Therefore, the fusion protein may be a useful tool to evaluate contributions of proteolytic activity of MMP-2 in various pathophysiological processes. It may also be developed as an effective anti-tumor drug with restricted side effects.

  17. Molecular design, synthesis and biological activities of amidines as new ketol-acid reductoisomerase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Bao Lei Wang; Yong Hong Li; Jian Guo Wang; Yi Ma; Zheng Ming Li

    2008-01-01

    Diamidine (A) was identified in our in vitro bio-assay as a possible inhibitor of ketol-acid reductoisomerase (KARI) from the ACD database search based on the known three-dimensional crystal structure of KARI. An investigation on interaction of A on KARI active sites, led to the design and synthesis of 15 novel monoamidines. Some of those showed better biological activity than A on rice KARI (in vitro) and in greenhouse herbicidal tests (in vivo). The structure-biological activity relationship was investigated, which provides valuable information to further study of potential KARI inhibitors.

  18. 3D-QSAR and molecular docking studies on designing inhibitors of the hepatitis C virus NS5B polymerase

    Science.gov (United States)

    Li, Wenlian; Si, Hongzong; Li, Yang; Ge, Cuizhu; Song, Fucheng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

    2016-08-01

    Viral hepatitis C infection is one of the main causes of the hepatitis after blood transfusion and hepatitis C virus (HCV) infection is a global health threat. The HCV NS5B polymerase, an RNA dependent RNA polymerase (RdRp) and an essential role in the replication of the virus, has no functional equivalent in mammalian cells. So the research and development of efficient NS5B polymerase inhibitors provides a great strategy for antiviral therapy against HCV. A combined three-dimensional quantitative structure-activity relationship (QSAR) modeling was accomplished to profoundly understand the structure-activity correlation of a train of indole-based inhibitors of the HCV NS5B polymerase to against HCV. A comparative molecular similarity indices analysis (COMSIA) model as the foundation of the maximum common substructure alignment was developed. The optimum model exhibited statistically significant results: the cross-validated correlation coefficient q2 was 0.627 and non-cross-validated r2 value was 0.943. In addition, the results of internal validations of bootstrapping and Y-randomization confirmed the rationality and good predictive ability of the model, as well as external validation (the external predictive correlation coefficient rext2 = 0.629). The information obtained from the COMSIA contour maps enables the interpretation of their structure-activity relationship. Furthermore, the molecular docking study of the compounds for 3TYV as the protein target revealed important interactions between active compounds and amino acids, and several new potential inhibitors with higher activity predicted were designed basis on our analyses and supported by the simulation of molecular docking. Meanwhile, the OSIRIS Property Explorer was introduced to help select more satisfactory compounds. The satisfactory results from this study may lay a reliable theoretical base for drug development of hepatitis C virus NS5B polymerase inhibitors.

  19. Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and Drug Design.

    Science.gov (United States)

    LeMaster, David M; Hernandez, Griselda

    2015-01-01

    Among the 22 FKBP domains in the human genome, FKBP12.6 and the first FKBP domains (FK1) of FKBP51 and FKBP52 are evolutionarily and structurally most similar to the archetypical FKBP12. As such, the development of inhibitors with selectivity among these four FKBP domains poses a significant challenge for structure-based design. The pleiotropic effects of these FKBP domains in a range of signaling processes such as the regulation of ryanodine receptor calcium channels by FKBP12 and FKBP12.6 and steroid receptor regulation by the FK1 domains of FKBP51 and FKBP52 amply justify the efforts to develop selective therapies. In contrast to their close structural similarities, these four FKBP domains exhibit a substantial diversity in their conformational flexibility. A number of distinct conformational transitions have been characterized for FKBP12 spanning timeframes from 20 s to 10 ns and in each case these dynamics have been shown to markedly differ from the conformational behavior for one or more of the other three FKBP domains. Protein flexibilitybased inhibitor design could draw upon the transitions that are significantly populated in only one of the targeted proteins. Both the similarities and differences among these four proteins valuably inform the understanding of how dynamical effects propagate across the FKBP domains as well as potentially how such intramolecular transitions might couple to the larger scale transitions that are central to the signaling complexes in which these FKBP domains function.

  20. Molecular designing of novel ternary copolymers of donor-acceptor polymers using genetic algorithm

    Science.gov (United States)

    Arora, Vinita; Bakhshi, A. K.

    2010-08-01

    An efficient designing route to novel ternary copolymers consisting of polypyrrole (PPy), polythiophene (PTh) and polyfuran (PFu) is developed with the help of genetic algorithm. Using the band structure results obtained from ab initio crystal orbital (CO) calculations, the electronic structures and conduction properties of real ternary copolymers based on donor acceptor type polymers are investigated. The electron rich heterocyclic rings in the backbone chain of the copolymer are joined together by electron withdrawing groups Y, carbonyl group (>C dbnd O) and difluoromethylene group (>C dbnd CF 2) in an attempt to design the conducting polymer with lowest band gap. A comparative study of various electronic properties is presented. The effects of substitution on the behaviour and properties of the copolymers as well as on the density of states (DOS) are discussed. Band gap decreases as a result of substitution on the polymer backbone chain due to decrease in ionization potential and increase in electron affinity values. This is expected to enhance the intrinsic conductivity of the resulting copolymer. Use of alternate donor acceptor moieties within the repeat units should maximize the extended π conjugation.

  1. Attachment, Stress, Dyadic Coping, and Marital Satisfaction of Counseling Graduate Students

    Science.gov (United States)

    Fuenfhausen, Kerrie K.; Cashwell, Craig S.

    2013-01-01

    A sample of 191 married students from 23 Council for Accreditation of Counseling and Related Educational Programs-accredited programs participated in a survey designed to examine factors that affect the marital satisfaction of counseling graduate students. Results indicated that attachment anxiety, attachment avoidance, and dyadic coping accounted…

  2. Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule.

    Science.gov (United States)

    Ahmadian, Haleh; Hansen, Ernst B; Faber, Johan H; Sejergaard, Lars; Karlsson, Johan; Bolt, Gert; Hansen, Jens J; Thim, Lars

    2016-07-01

    Turoctocog alfa (NovoEight) is a third-generation recombinant factor VIII (rFVIII) with a truncated B-domain that is manufactured in Chinese hamster ovary cells. No human or animal-derived materials are used in the process. The aim of this study is to describe the molecular design and purification process for turoctocog alfa. A five-step purification process is applied to turoctocog alfa: protein capture on mixed-mode resin; immunoaffinity chromatography using a unique, recombinantly produced anti-FVIII mAb; anion exchange chromatography; nanofiltration and size exclusion chromatography. This process enabled reduction of impurities such as host cell proteins (HCPs) and high molecular weight proteins (HMWPs) to a very low level. The immunoaffinity step is very important for the removal of FVIII-related degradation products. Manufacturing scale data shown in this article confirmed the robustness of the purification process and a reliable and consistent reduction of the impurities. The contribution of each step to the final product purity is described and shown for three manufacturing batches. Turoctocog alfa, a third-generation B-domain truncated rFVIII product is manufactured in Chinese hamster ovary cells without the use of animal or human-derived proteins. The five-step purification process results in a homogenous, highly purified rFVIII product.

  3. Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents.

    Science.gov (United States)

    Ramprasad, Jurupula; Nayak, Nagabhushana; Dalimba, Udayakumar

    2015-12-01

    A new library of phenothiazine and 1,3,4-thiadiazole hybrid derivatives (5a-u) was designed based on the molecular hybridization approach and the molecules were synthesized in excellent yields using a facile single-step chloro-amine coupling reaction between 2-chloro-1-(10H-phenothiazin-10-yl)ethanones and 2-amino-5-subsituted-1,3,4-thiadiazoles. The compounds were evaluated for their in vitro inhibition activity against Mycobacterium tuberculosis H37Rv (MTB). Compounds 5 g and 5 n were emerged as the most active compounds of the series with MIC of 0.8 μg/mL (∼ 1.9 μM). Also, compounds 5a, 5b, 5c, 5e, 5l and 5m (MIC = 1.6 μg/mL), and compounds 5j, 5k and 5o (MIC = 3.125 μg/mL) showed significant inhibition activity. The structure-activity relationship demonstrated that an alkyl (methyl/n-propyl) or substituted (4-methyl/4-Cl/4-F) phenyl groups on the 1,3,4-thiadiazole ring enhance the inhibition activity of the compounds. The cytotoxicity study revealed that none of the active molecules are toxic to a normal Vero cell line thus proving the lack of general cellular toxicity. Further, the active molecules were subjected to molecular docking studies with target enzymes InhA and CYP121.

  4. Benefits of statistical molecular design, covariance analysis, and reference models in QSAR: a case study on acetylcholinesterase.

    Science.gov (United States)

    Andersson, C David; Hillgren, J Mikael; Lindgren, Cecilia; Qian, Weixing; Akfur, Christine; Berg, Lotta; Ekström, Fredrik; Linusson, Anna

    2015-03-01

    Scientific disciplines such as medicinal- and environmental chemistry, pharmacology, and toxicology deal with the questions related to the effects small organic compounds exhort on biological targets and the compounds' physicochemical properties responsible for these effects. A common strategy in this endeavor is to establish structure-activity relationships (SARs). The aim of this work was to illustrate benefits of performing a statistical molecular design (SMD) and proper statistical analysis of the molecules' properties before SAR and quantitative structure-activity relationship (QSAR) analysis. Our SMD followed by synthesis yielded a set of inhibitors of the enzyme acetylcholinesterase (AChE) that had very few inherent dependencies between the substructures in the molecules. If such dependencies exist, they cause severe errors in SAR interpretation and predictions by QSAR-models, and leave a set of molecules less suitable for future decision-making. In our study, SAR- and QSAR models could show which molecular sub-structures and physicochemical features that were advantageous for the AChE inhibition. Finally, the QSAR model was used for the prediction of the inhibition of AChE by an external prediction set of molecules. The accuracy of these predictions was asserted by statistical significance tests and by comparisons to simple but relevant reference models.

  5. Design, development, and use of molecular primers and probes for the detection of Gluconacetobacter species in the pink sugarcane mealybug.

    Science.gov (United States)

    Franke-Whittle, Ingrid H; O'Shea, Michael G; Leonard, Graham J; Sly, Lindsay I

    2005-07-01

    Molecular tools for the species-specific detection of Gluconacetobacter sacchari, Gluconacetobacter diazotrophicus, and Gluconacetobacter liquefaciens from the pink sugarcane mealybug (PSMB) Saccharicoccus sacchari Cockerell (Homiptera: Pseudococcidae) were developed and used in polymerase chain reactions (PCR) and in fluorescence in situ hybridizations (FISH) to better understand the microbial diversity and the numerical significance of the acetic acid bacteria in the PSMB microenvironment. The presence of these species in the PSMB occurred over a wide range of sites, but not in all sites in sugarcane-growing areas of Queensland, Australia, and was variable over time. Molecular probes for use in FISH were also designed for the three acetic acid bacterial species, and shown to be specific only for the target species. Use of these probes in FISH of "squashed" whole mealybugs indicated that these acetic acid bacteria species represent only a small proportion of the microbial population of the PSMB. Despite the detection of Glac. sacchari, Glac. diazotrophicus, and Glac. liquefaciens by PCR from different mealybugs isolated at various times and from various sugarcane-growing areas in Queensland, Australia, these bacteria do not appear to be significant commensals in the PSMB environment.

  6. Accessing the Long-Lived Triplet Excited States in Transition-Metal Complexes: Molecular Design Rationales and Applications.

    Science.gov (United States)

    Cui, Xiaoneng; Zhao, Jianzhang; Mohmood, Zafar; Zhang, Caishun

    2016-02-01

    Transition-metal complex triplet photosensitizers are versatile compounds that have been widely used in photocatalysis, photovoltaics, photodynamic therapy (PDT) and triplet-triplet annihilation (TTA) upconversion. The principal photophysical processes in these applications are the intermolecular energy transfer or electron transfer. One of the major challenges facing these triplet photosensitizers is the short triplet-state lifetime, which is detrimental to the above-mentioned photophysical processes. In order to address this challenge, transition-metal complexes showing long-lived triplet excited states are highly desired. This review article summarizes the development of this fascinating area, including the molecular design rationales, the principal photophysical properties, and the applications of these complexes in PDT and TTA upconversion.

  7. Optimal drug cocktail design: methods for targeting molecular ensembles and insights from theoretical model systems.

    Science.gov (United States)

    Radhakrishnan, Mala L; Tidor, Bruce

    2008-05-01

    Drug resistance is a significant obstacle in the effective treatment of diseases with rapidly mutating targets, such as AIDS, malaria, and certain forms of cancer. Such targets are remarkably efficient at exploring the space of functional mutants and at evolving to evade drug binding while still maintaining their biological role. To overcome this challenge, drug regimens must be active against potential target variants. Such a goal may be accomplished by one drug molecule that recognizes multiple variants or by a drug "cocktail"--a small collection of drug molecules that collectively binds all desired variants. Ideally, one wants the smallest cocktail possible due to the potential for increased toxicity with each additional drug. Therefore, the task of designing a regimen for multiple target variants can be framed as an optimization problem--find the smallest collection of molecules that together "covers" the relevant target variants. In this work, we formulate and apply this optimization framework to theoretical model target ensembles. These results are analyzed to develop an understanding of how the physical properties of a target ensemble relate to the properties of the optimal cocktail. We focus on electrostatic variation within target ensembles, as it is one important mechanism by which drug resistance is achieved. Using integer programming, we systematically designed optimal cocktails to cover model target ensembles. We found that certain drug molecules covered much larger regions of target space than others, a phenomenon explained by theory grounded in continuum electrostatics. Molecules within optimal cocktails were often dissimilar, such that each drug was responsible for binding variants with a certain electrostatic property in common. On average, the number of molecules in the optimal cocktails correlated with the number of variants, the differences in the variants' electrostatic properties at the binding interface, and the level of binding affinity

  8. Rational Molecular Design of Potent PLK1 PBD Domain-binding Phosphopeptides Using Preferential Amino Acid Building Blocks.

    Science.gov (United States)

    Mao, Xin-Li; Wang, Kui-Feng; Zhu, Feng; Pan, Zhao-Hu; Wu, Guo-Min; Zhu, Hong-Yuan

    2016-08-01

    Polo-like kinase 1 (PLK1) is an important regulator in diverse aspects of the cell cycle and proliferation. The protein has a highly conserved polo-box domain (PBD) present in C-terminal noncatalytic region, which exhibits a relatively broad sequence specificity in recognizing and binding phosphorylated substrates to control substrate phosphorylation by the kinase. In order to elucidate the structural basis, thermodynamic property, and biological implication underlying PBD-substrate recognition and association, a systematic amino acid preference profile of phosphopeptide interaction with PLK1 PBD domain was established via virtual mutagenesis analysis and mutation energy calculation, from which the contribution of different amino acids at each residue position of two reference phosphopeptides to domain-peptide binding was characterized comprehensively and quantitatively. With the profile, we are able to determine the favorable, neutral, and unfavorable amino acid types for each position of PBD-binding phosphopeptides, and we also explored the molecular origin of the broad sequence specificity in PBD-substrate recognition. To practice computational findings, the profile was further employed to guide rational design of potent PBD binders; three 6-mer phosphopeptides (i.e., IQSpSPC, LQSpTPF, and LNSpTPT) were successfully developed, which can efficiently target PBD domain with high affinity (Kd = 5.7 ± 1.1, 0.75 ± 0.18, and 7.2 ± 2.6 μm, resp.) as measured by a fluorescence anisotropy assay. The complex structure of PLK1 PBD domain with a newly designed, potent phosphopeptide LQSpTPF as well as diverse noncovalent chemical forces, such as H-bonds and hydrophobic interactions at the complex interface, were examined in detail to reveal the molecular mechanism of high affinity and stability of the complex system.

  9. Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly.

    Science.gov (United States)

    Khamaikawin, Wannisa; Saoin, Somphot; Nangola, Sawitree; Chupradit, Koollawat; Sakkhachornphop, Supachai; Hadpech, Sudarat; Onlamoon, Nattawat; Ansari, Aftab A; Byrareddy, Siddappa N; Boulanger, Pierre; Hong, Saw-See; Torbett, Bruce E; Tayapiwatana, Chatchai

    2015-08-25

    Designed molecular scaffolds have been proposed as alternative therapeutic agents against HIV-1. The ankyrin repeat protein (Ank(GAG)1D4) and the zinc finger protein (2LTRZFP) have recently been characterized as intracellular antivirals, but these molecules, used individually, do not completely block HIV-1 replication and propagation. The capsid-binder Ank(GAG)1D4, which inhibits HIV-1 assembly, does not prevent the genome integration of newly incoming viruses. 2LTRZFP, designed to target the 2-LTR-circle junction of HIV-1 cDNA and block HIV-1 integration, would have no antiviral effect on HIV-1-infected cells. However, simultaneous expression of these two molecules should combine the advantage of preventive and curative treatments. To test this hypothesis, the genes encoding the N-myristoylated Myr(+)Ank(GAG)1D4 protein and the 2LTRZFP were introduced into human T-cells, using a third-generation lentiviral vector. SupT1 cells stably expressing 2LTRZFP alone or with Myr(+)Ank(GAG)1D4 showed a complete resistance to HIV-1 in viral challenge. Administration of the Myr(+)Ank(GAG)1D4 vector to HIV-1-preinfected SupT1 cells resulted in a significant antiviral effect. Resistance to viral infection was also observed in primary human CD4+ T-cells stably expressing Myr(+)Ank(GAG)1D4, and challenged with HIV-1, SIVmac, or SHIV. Our data suggest that our two anti-HIV-1 molecular scaffold prototypes are promising antiviral agents for anti-HIV-1 gene therapy.

  10. Enzyme molecular dynamics simulations in different solvents: Fundamental effects and a new paradigm for rational design

    Energy Technology Data Exchange (ETDEWEB)

    Ornstein, R.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-12-31

    Developing enzymes that are functional in nonaqueous solutions may prove useful in the development of new strategies for environmental remediation and monitoring, as well as in developing `green` processes. To gain a fundamental understanding of the structural and dynamic consequences to an enzyme induced by such solvents, we compared simulation results for the well characterized protease enzyme subtilisin Carlsberg in different solvents, including water, carbon tetrachloride, and dimethyl sulfoxide. Serendipitously, we observed a small number of solvent-dependent `tight-binding` site between the enzyme and each solvent. Such solvent-dependent `tight-binding` site information may offer a new simulation paradigm for protein engineering and drug design. Examples will be offered for the cases of subtilisin and a glutathione S-transferase.

  11. Parental programming: how can we improve study design to discern the molecular mechanisms?

    Science.gov (United States)

    Lecomte, Virginie; Youngson, Neil A; Maloney, Christopher A; Morris, Margaret J

    2013-09-01

    The contribution of inherited non-genetic factors to complex diseases is of great current interest. The ways in which mothers and fathers can affect their offspring's health clearly differ as a result of the intimate interactions between mother and offspring during pre- and postnatal life. There is, however, potential for some overlap in mechanisms, particularly epigenetic mechanisms. A small number of epidemiological studies and animal models have investigated the non-genetic contribution of the parents to offspring health. Discovering new mechanisms of disease inheritance is technically difficult, especially in genetically, socially and environmentally heterogeneous human populations. Therefore, rigorous experimental design, appropriate sample numbers and the use of high-throughput technologies are necessary to provide convincing evidence. Based on recent examples from the literature, here we propose several ways to improve human studies that aim to identify the underlying mechanisms of transgenerational inheritance of metabolic disease.

  12. Molecular design of organic dyes based on vinylene hexylthiophene bridge for dye-sensitized solar cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Three donor-(π-spacer)-acceptor(D-π-A) organic dyes,containing different groups(triphenylamine,di(p-tolyl)phenylamine,and 9-octylcarbazole moieties) as electron donors,were designed and synthesized.Nanocrystalline TiO2 dye-sensitized solar cells were fabricated by using these dyes.It was found that the variation of electron donors in the D-π-A dyes played an important role in modifying and tuning photophysical properties of organic dyes.Under standard global AM 1.5 solar condition,the DSSC based on the dye D2 showed the best photovoltaic performance:a short-circuit photocurrent density(Jsc) of 13.93 mA/cm2,an open-circuit photovoltage(Voc) of 0.71 V,and a fill factor(FF) of 0.679,corresponding to solar-to-electric power conversion efficiency(η) of 6.72%.

  13. Molecular design of organic dyes based on vinylene hexylthiophene bridge for dye-sensitized solar cells

    Institute of Scientific and Technical Information of China (English)

    LIU DaXi; ZHAO Bin; SHEN Ping; HUANG Hui; LIU LiMing; TAN SongTing

    2009-01-01

    Three donor-(TT-spacer)-acceptor (D-tt-A) organic dyes,containing different groups (triphenylamine,di(p-tolyl)phenylamine,and 9-octylcarbazole moieties) as electron donors,were designed and synthesized. Nanocrystalline TiO2 dye-sensitized solar cells were fabricated by using these dyes. It was found that the variation of electron donors in the D-tt-A dyes played an important role in modifying and tuning photophysical properties of organic dyes. Under standard global AM 1.5 solar condition,the DSSC based on the dye D2 showed the best photovoltaic performance: a short-circuit photocurrent density (Jsc) of 13.93 mA/cm2,an open-circuit photovoltage (Voc) of 0.71 V,and a fill factor (FF) of 0.679,corresponding to solar-to-electric power conversion efficiency (77) of 6.72%.

  14. Molecular Design, Synthesis and Trypanocidal Activity of Dipeptidyl Nitriles as Cruzain Inhibitors.

    Science.gov (United States)

    Avelar, Leandro A A; Camilo, Cristian D; de Albuquerque, Sérgio; Fernandes, William B; Gonçalez, Cristiana; Kenny, Peter W; Leitão, Andrei; McKerrow, James H; Montanari, Carlos A; Orozco, Erika V Meñaca; Ribeiro, Jean F R; Rocha, Josmar R; Rosini, Fabiana; Saidel, Marta E

    2015-01-01

    A series of compounds based on the dipeptidyl nitrile scaffold were synthesized and assayed for their inhibitory activity against the T. cruzi cysteine protease cruzain. Structure activity relationships (SARs) were established using three, eleven and twelve variations respectively at the P1, P2 and P3 positions. A Ki value of 16 nM was observed for the most potent of these inhibitors which reflects a degree of non-additivity in the SAR. An X-ray crystal structure was determined for the ligand-protein complex for the structural prototype for the series. Twenty three inhibitors were also evaluated for their anti-trypanosomal effects and an EC50 value of 28 μM was observed for the most potent of these. Although there remains scope for further optimization, the knowledge gained from this study is also transferable to the design of cruzain inhibitors based on warheads other than nitrile as well as alternative scaffolds.

  15. Molecular designing of novel ternary copolymers of donor-acceptor polymers using genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Arora, Vinita [Department of Chemistry, University of Delhi, Delhi 110 007 (India); Bakhshi, A.K., E-mail: akbakhshi2000@yahoo.com [Department of Chemistry, University of Delhi, Delhi 110 007 (India)

    2010-08-03

    Graphical abstract: Alternate arrangement of donor acceptor moieties in the carbon backbone chain of an organic conjugated polymer is capable of inducing charge transfer and affects the electronic properties of the copolymer. Genetic algorithm along with simple NFC (negative factor counting) and IIM (inverse iteration method) has been used to optimize the properties of novel ternary copolymers based on polypyrrole PPy, polythiophene PTh and polyfuran PFu (as donor moieties) and containing >C=O and >C=CF{sub 2} bridging units as acceptor moieties. - Abstract: An efficient designing route to novel ternary copolymers consisting of polypyrrole (PPy), polythiophene (PTh) and polyfuran (PFu) is developed with the help of genetic algorithm. Using the band structure results obtained from ab initio crystal orbital (CO) calculations, the electronic structures and conduction properties of real ternary copolymers based on donor acceptor type polymers are investigated. The electron rich heterocyclic rings in the backbone chain of the copolymer are joined together by electron withdrawing groups Y, carbonyl group (>C=O) and difluoromethylene group (>C=CF{sub 2}) in an attempt to design the conducting polymer with lowest band gap. A comparative study of various electronic properties is presented. The effects of substitution on the behaviour and properties of the copolymers as well as on the density of states (DOS) are discussed. Band gap decreases as a result of substitution on the polymer backbone chain due to decrease in ionization potential and increase in electron affinity values. This is expected to enhance the intrinsic conductivity of the resulting copolymer. Use of alternate donor acceptor moieties within the repeat units should maximize the extended {pi} conjugation.

  16. A statistical investigation of the relationship between personal attachment style and satisfaction with evangelical church membership.

    Science.gov (United States)

    Hamilton, Scott; Martin, Magy; Martin, Don

    2012-12-01

    The purpose of this study was to examine if parishioners' relational attachment style influences their satisfaction with evangelical church membership. A sample of parishioners aged 18 and over completed the Relationship Questionnaire and the Congregation Satisfaction Questionnaire (CSQ), along with an accompanying demographic profile. The research design employed a one-way analysis of variance to determine if securely attached persons reported greater satisfaction with their evangelical church participation than those who reported preoccupied, dismissing, or fearful attachment. This study furthered existing research, suggesting that attachment style influences how people measure congregational satisfaction. In this study, securely attached individuals reported greater satisfaction, as measured by the CSQ, with their evangelical church membership than those who were not securely attached.

  17. [Attachment Patterns and their Relation to the Development of Anxiety Symptoms in Childhood and Adolescence].

    Science.gov (United States)

    Achtergarde, Sandra; Müller, Jörg Michael; Postert, Christian; Wessing, Ida; Mayer, Andreas; Romer, Georg

    2015-01-01

    From the perspective of attachment theory, insecure attachment can be seen as a key risk factor for the development of anxiety symptoms and anxiety disorders. This systematic review addresses the current state of empirical research on the relationship between attachment status and anxiety symptoms respective anxiety disorders in childhood and adolescence. 21 current international studies published between 2010 and 2014 were included in this systematic review. These studies were heterogeneous in target populations, methods and study design. The majority of studies supported the assumed correlation between insecure attachment and anxiety symptoms or anxiety disorders. These findings are more evident in studies with school-age children than with preschool children or adolescents. Furthermore, the disorganized-disoriented type of attachment seems to be a particular risk factor for the development of anxiety symptoms and anxiety disorders. Results were discussed in relation to attachment theory and with reference to the results of previous relevant reviews.

  18. Antecedents of maternal parenting stress: the role of attachment style, prenatal attachment and dyadic adjustment in first-time mothers

    Directory of Open Access Journals (Sweden)

    Claudia eMazzeschi

    2015-09-01

    Full Text Available The transition to parenthood is widely considered a period of increased vulnerability often accompanied by stress. Abidin conceived parenting stress as referring to specific difficulties in adjusting to the parenting role. Most studies of psychological distress arising from the demands of parenting have investigated the impact of stress on the development of dysfunctional parent-child relationships and on adult and child psychopathology. Studies have largely focused on mothers’ postnatal experience; less attention has been devoted to maternal prenatal characteristics associated with the subsequent parental stress and studies of maternal prenatal predictors are few. Furthermore, no studies have examined that association exclusively with samples of first-time mothers. With an observational prospective study design with two time periods, the aim of this study was to investigate the role of mothers’ attachment style, maternal prenatal attachment to the fetus and dyadic adjustment during pregnancy (7th month of gestation and their potential unique contribution to parenting stress three months after childbirth in a sample of nulliparous women. Results showed significant correlations between antenatal measures. Maternal attachment style (especially relationship anxiety was negatively correlated with prenatal attachment and with dyadic adjustment; positive correlations resulted between prenatal attachment and dyadic adjustment. Each of the investigated variables was also good predictor of parenting stress three months after childbirth. Findings suggested how these dimensions could be considered as risk factors in the transition to motherhood and in the very beginning of the emergence of the caregiving system, especially with first-time mothers

  19. Antecedents of maternal parenting stress: the role of attachment style, prenatal attachment, and dyadic adjustment in first-time mothers.

    Science.gov (United States)

    Mazzeschi, Claudia; Pazzagli, Chiara; Radi, Giulia; Raspa, Veronica; Buratta, Livia

    2015-01-01

    The transition to parenthood is widely considered a period of increased vulnerability often accompanied by stress. Abidin conceived parenting stress as referring to specific difficulties in adjusting to the parenting role. Most studies of psychological distress arising from the demands of parenting have investigated the impact of stress on the development of dysfunctional parent-child relationships and on adult and child psychopathology. Studies have largely focused on mothers' postnatal experience; less attention has been devoted to maternal prenatal characteristics associated with subsequent parental stress and studies of maternal prenatal predictors are few. Furthermore, no studies have examined that association exclusively with samples of first-time mothers. With an observational prospective study design with two time periods, the aim of this study was to investigate the role of mothers' attachment style, maternal prenatal attachment to the fetus and dyadic adjustment during pregnancy (7th months of gestation) and their potential unique contribution to parenting stress 3 months after childbirth in a sample of nulliparous women. Results showed significant correlations between antenatal measures. Maternal attachment style (especially relationship anxiety) was negatively correlated with prenatal attachment and with dyadic adjustment; positive correlations resulted between prenatal attachment and dyadic adjustment. Each of the investigated variables was also good predictor of parenting stress 3 months after childbirth. Findings suggested how these dimensions could be considered as risk factors in the transition to motherhood and in the very beginning of the emergence of the caregiving system, especially with first-time mothers.

  20. Control over Structure and Function of Peptide Amphiphile Supramolecular Assemblies through Molecular Design and Energy Landscapes

    Science.gov (United States)

    Tantakitti, Faifan

    Supramolecular chemistry is a powerful tool to create a material of a defined structure with tunable properties. This strategy has led to catalytically active, bioactive, and environment-responsive materials, among others, that are valuable in applications ranging from sensor technology to energy and medicine. Supramolecular polymers formed by peptide amphiphiles (PAs) have been especially relevant in tissue regeneration due to their ability to form biocompatible structures and mimic many important signaling molecules in biology. These supramolecular polymers can form nanofibers that create networks which mimic natural extracellular matrices. PA materials have been shown to induce growth of blood vessels, bone, cartilage, and nervous tissue, among others. The work described in this thesis not only studied the relationship between molecular structure and functions of PA assemblies, but also uncovered a powerful link between the energy landscape of their supramolecular self-assembly and the ability of PA materials to interact with cells. In chapter 2, it is argued that fabricating fibrous nanostructures with defined mechanical properties and decoration with bioactive molecules is not sufficient to create a material that can effectively communicate with cells. By systemically placing the fibronectin-derived RGDS epitope at increasing distances from the surface of PA nanofibers through a linker of one to five glycine residues, integrin-mediated RGDS signaling was enhanced. The results suggested that the spatial presentation of an epitope on PA nanofibers strongly influences the bioactivity of the PA substrates. In further improving functionality of a PA-based scaffold to effectively direct cell growth and differentiation, chapter 3 explored the use of a cell microcarrier to compartmentalize and simultaneously tune insoluble and soluble signals in a single matrix. PA nanofibers were incorporated at the surface of the microcarrier in order to promote cell adhesion, while