WorldWideScience

Sample records for attached molecular design

  1. Jet-diffuser Ejector - Attached Nozzle Design

    Science.gov (United States)

    Alperin, M.; Wu, J. J.

    1980-01-01

    Attached primary nozzles were developed to replace the detached nozzles of jet-diffuser ejectors. Slotted primary nozzles located at the inlet lip and injecting fluid normal to the thrust axis, and rotating the fluid into the thrust direction using the Coanda Effect were investigated. Experiments indicated excessive skin friction or momentum cancellation due to impingement of opposing jets resulted in performance degradation. This indicated a desirability for location and orientation of the injection point at positions removed from the immediate vicinity of the inlet surface, and at an acute angle with respect to the thrust axis. Various nozzle designs were tested over a range of positions and orientations. The problems of aircraft integration of the ejector, and internal and external nozzle losses were also considered and a geometry for the attached nozzles was selected. The effect of leaks, protrusions, and asymmetries in the ejector surfaces was examined. The results indicated a relative insensitivity to all surface irregularities, except for large protrusions at the throat of the ejector.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Attachments

    International Nuclear Information System (INIS)

    In this attachment to the Annual report 1999 of the Nuclear Regulatory Authority of the Slovak Republic (UJD) the economic and personnel data of the UJD, used abbreviations, as well as the International nuclear event scales - INES are presented. Professional level of staff of the UJD is influenced by the education structure of its staff, when nearly 75% of the total number of staff has a university degree. A of 31.12.1999 there were 79 employees as average calculated number. Financing of the regulator in 1999 was mainly provided from the state budget, which represented 96% of all expenditures. The total volume of expenditures for UJD activity funded from the state budget achieved as of 31.12.1999 Slovak crowns (SK) 67 067 thousands. In the main category of expenditures an amount of SK 63 499 thous. was used for current activities, and the difference of SK 3 587 thous. was used for raising capital assets. Significant increase expenditures in the evaluated year compared to the 1998 was caused by a special purpose payment made by the Slovakia into the Fund for reconstruction of the Chernobyl cover (SK 19 996 thous.) funded through the budget chapter of the regulator. In the structure of current expenditures the highest share is taken by current transfers to abroad in total of SK 22 543 thous., i.e. contribution to reconstruction of Chernobyl cover made to the EBRD and contributions to the Fund of Technical Co-operation of the IAEA. For procurement of goods and services an amount of SK 19 814 thous. was spent, of which SK 7 054 thous. was used for funding science and technology tasks which were contracted out. The decision-making process in performing state supervision forced UJD to contact out various expert opinions and studies, for which UJD paid SK 2 058 thous. in total. Other expenditures in a volume of SK 10 702 thous. represent travel expenses, goods and services for UJD, rent for offices and other inevitable expenses. Salaries of staff represented SK 15 953

  7. DESIGN OF A PORTABLE AND ATTACHABLE BABY COT

    OpenAIRE

    SOWAH BORIS NII-AKO; CLETUS FIIFI AD; BERNARD OWUSU ASIMENG; ELSIE EFFAH KAUFMANN

    2013-01-01

    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...

  8. 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.

  9. 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.

  10. Dual-shank attachment design for omega seals

    Science.gov (United States)

    Sattinger, Stanley S.

    1978-01-01

    An improved apparatus and process for attaching welded omega seal segments to reactor heads, standpipes, mechanisms, and plugs comprises a first shank in combination with a second shank to attach an omega seal at a metal-to-metal interface.

  11. Design and Development of Attachment for Hydraulic Stacker

    OpenAIRE

    S.H. Gawande; A.A. Arole; K.H. Barhate,; R.P. Gujar; M. Viroff

    2010-01-01

    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 up...

  12. Highly Transient Molecular Interactions Underlie the Stability of Kinetochore–Microtubule Attachment During Cell Division

    Science.gov (United States)

    Zaytsev, Anatoly V.; Ataullakhanov, Fazly I.; Grishchuk, Ekaterina L.

    2013-01-01

    Chromosome segregation during mitosis is mediated by spindle microtubules that attach to chromosomal kinetochores with strong yet labile links. The exact molecular composition of the kinetochore–microtubule interface is not known but microtubules are thought to bind to kinetochores via the specialized microtubule-binding sites, which contain multiple microtubule-binding proteins. During prometaphase the lifetime of microtubule attachments is short but in metaphase it increases 3-fold, presumably owing to dephosphorylation of the microtubule-binding proteins that increases their affinity. Here, we use mathematical modeling to examine in quantitative and systematic manner the general relationships between the molecular properties of microtubule-binding proteins and the resulting stability of microtubule attachment to the protein-containing kinetochore site. We show that when the protein connections are stochastic, the physiological rate of microtubule turnover is achieved only if these molecular interactions are very transient, each lasting fraction of a second. This “microscopic” time is almost four orders of magnitude shorter than the characteristic time of kinetochore–microtubule attachment. Cooperativity of the microtubule-binding events further increases the disparity of these time scales. Furthermore, for all values of kinetic parameters the microtubule stability is very sensitive to the minor changes in the molecular constants. Such sensitivity of the lifetime of microtubule attachment to the kinetics and cooperativity of molecular interactions at the microtubule-binding site may hinder the accurate regulation of kinetochore–microtubule stability during mitotic progression, and it necessitates detailed experimental examination of the microtubule-binding properties of kinetochore-localized proteins. PMID:24376473

  13. Highly Transient Molecular Interactions Underlie the Stability of Kinetochore-Microtubule Attachment During Cell Division.

    Science.gov (United States)

    Zaytsev, Anatoly V; Ataullakhanov, Fazly I; Grishchuk, Ekaterina L

    2013-12-13

    Chromosome segregation during mitosis is mediated by spindle microtubules that attach to chromosomal kinetochores with strong yet labile links. The exact molecular composition of the kinetochore-microtubule interface is not known but microtubules are thought to bind to kinetochores via the specialized microtubule-binding sites, which contain multiple microtubule-binding proteins. During prometaphase the lifetime of microtubule attachments is short but in metaphase it increases 3-fold, presumably owing to dephosphorylation of the microtubule-binding proteins that increases their affinity. Here, we use mathematical modeling to examine in quantitative and systematic manner the general relationships between the molecular properties of microtubule-binding proteins and the resulting stability of microtubule attachment to the protein-containing kinetochore site. We show that when the protein connections are stochastic, the physiological rate of microtubule turnover is achieved only if these molecular interactions are very transient, each lasting fraction of a second. This "microscopic" time is almost four orders of magnitude shorter than the characteristic time of kinetochore-microtubule attachment. Cooperativity of the microtubule-binding events further increases the disparity of these time scales. Furthermore, for all values of kinetic parameters the microtubule stability is very sensitive to the minor changes in the molecular constants. Such sensitivity of the lifetime of microtubule attachment to the kinetics and cooperativity of molecular interactions at the microtubule-binding site may hinder the accurate regulation of kinetochore-microtubule stability during mitotic progression, and it necessitates detailed experimental examination of the microtubule-binding properties of kinetochore-localized proteins. PMID:24376473

  14. 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.

  15. 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

  16. 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)

  17. Inverse strategies for molecular design

    International Nuclear Information System (INIS)

    An 'inverse' molecular design strategy is described to assist in the development of new molecules with optimized properties. This approach is based on a molecular orbital view and can be used to tailor ground state or excited state properties subject to particular constrains. In this scheme, wave functions are sought that optimize a chemical or electronic property, and then a Hamiltonian is constructed that generates these optimized wave functions. Analysis of the chemical properties in the optimized systems may suggest new synthetic targets. Examples are presented that optimize the transition dipole moment in some simple structures. 15 refs., 6 figs

  18. Comparison of the FRM-II HEU design with an alternative LEU design. Attachment

    International Nuclear Information System (INIS)

    After presentation of the foregoing paper by Dr. Nelson Hanan of Argonne National Laboratory (ANL) proposing an alternative LEU core with one fuel ring and a power level of 33 MW, a presentation was made by Dr. Klaus Boning of the Technical University of Munich comparing the FRM-II HEU design with an LEU design by Tlm that had two fuel rings and a power level of 40 MW. Dr. Boning raised the following issues concerning the use of LEU fuel in FRM-H reactor designs: (1) qualification of HEU and LEU silicide fuels, (2) gamma heating in the heavy water reflector, (3) the radiological consequences of hypothetical accidents, and (4) cost and schedule. These issues are addressed in this Attachment. In his presentation, Dr. Hanan mentioned that ANL was also investigating other LEU designs. This work led to a second alternative LEU design that has the same neutron flux performance (8 x 1014 n/cm2/s peak neutron flux in the reflector) and the same fuel lifetime (50 full power days) as the HEU design, but uses LEU silicide fuel with a uranium density of only 4.5 g/cm3. This design was achieved by using a fuel plate that has a fuel meat thickness of 0.76 mm, a cladding thickness of 0.38 mm, and a water channel gap of 2.2 mm. A comparison is shown of the main characteristics of this second alternative LEU design with those of the FRM-II HEU design. The ANL core again has one fuel ring with the same dimensions. With this LEU design, a two stage process is no longer necessary because LEU silicide fuel with a uranium density of 4.5 g/cm3 is fully qualified, licensable, and available now for use in a high flux reactor such as the FRM-II

  19. 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.

  20. 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...

  1. Application of a modified harness design for attachment of radio transmitters to shorebirds

    Science.gov (United States)

    Sanzenbacher, Peter; Haig, Susan M.; Oring, L.W.

    2000-01-01

    Radio transmitter attachment methodology is important to the design of radio telemetry studies. In 1998, we attached 5 transmitters to a captive population of Western Sandpipers(Calidris mauri) and 7 transmitters to wild Killdeer (Charadriusv ociferus) using a modified version of the Rappolea nd Tipton (1991) figure-8 leg-loop harness. Captive birds fitted with harnesses did not exhibit quantifiable differences in behavior relative to control birds. Based on initial success in using the leg-loop harnesses, we used harnesses to attach transmitters in the wild to 30 Killdeer and 49 Dunlin (Calidris alpina) during the winters of 1998-1999 and 1999-2000. This was part of a study on movements of wintering shorebirds in the Willamette Valley of Oregon,USA. Wild birds showed no adverse effects of the harnesses.Thus, the described harness is a practical method for attachment of transmitters to shorebirds. Advantages of this harness method include a reduction in handling time at capture, elimination of the need to clip feathers for attachment, and increased transmitter retention time.

  2. 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).

  3. Formation of carbon chain molecular anions by radiative electron attachment and their destruction by photodetachment

    Science.gov (United States)

    Khamesian, Marjan; Douguet, Nicolas; Raoult, Maurice; Dulieu, Olivier; Kokoouline, Viatcheslav

    2016-05-01

    Several negative ions Cn H- (n = 4 , 6 , 8), Cn N- (n = 1 , 3 , 5) have been recently observed in the interstellar medium (ISM). A possible mechanism of formation is radiative electron attachment (REA). In this study we develop a first principle theoretical approach to study the REA and apply the approach to the formation of the negative molecular ions CN-, C2 H-, C3 N-, C4 H-, C5 N-, C6 H-, and C8 H-. The theoretical approach is based on the UK R-matrix calculations. Cross sections and rate coefficients for formation of these ions by REA to the corresponding neutral radicals are calculated. There is no experimental data on REA of these ions. However, using a similar approach we have also calculated cross sections for photodetachment of the negative ions and compared the obtained results with available experimental data. The good agreement with photodetachment experimental data provides a confirmation that the REA cross sections obtained in this study is also reliable. NSF Grant PHYS-1506391.

  4. 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.

  5. Bacterial Attachment to Polymeric Materials Correlates with Molecular Flexibility and Hydrophilicity

    OpenAIRE

    Sanni, Olutoba; Chang, Chien-Yi; Anderson, Daniel G.; Langer, Robert; Davies, Martyn C.; Williams, Philip M; Williams, Paul; Alexander, Morgan R.; Hook, Andrew L.

    2014-01-01

    A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials' pendant groups. This...

  6. Design of underwater video attached to buoy for observing shallow water substrate

    Science.gov (United States)

    Dingtian, Y.; Wenxi, C.; Delu, P.

    2007-01-01

    Knowledge of shallow water substrate is very important for protection and management of coastal ecosystem. Traditional methods for observing shallow water substrate was by sending diver to photography and recorded with eye, which was laborious and money taking. In order to obtain the easier way to study the shallow water substrate, an underwater video system was designed. Underwater video sensor, optical sensor, sonar sensor, tiltometer, GPS system, and ascending and descending system were all attached to the buoy system, and data was gathered and processed by the computer on the ship. The obtained data could be used for analyzing substrate type, activity of benthos and ground truth data for satellite remote sensing.

  7. 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.

  8. Bacterial attachment to polymeric materials correlates with molecular flexibility and hydrophilicity.

    Science.gov (United States)

    Sanni, Olutoba; Chang, Chien-Yi; Anderson, Daniel G; Langer, Robert; Davies, Martyn C; Williams, Philip M; Williams, Paul; Alexander, Morgan R; Hook, Andrew L

    2015-04-01

    A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials' pendant groups. This correlation is applicable to 86% of the hydrocarbon pendant moieties surveyed, quantitatively supporting the previous qualitative observation that bacteria are repelled from poly(meth)acrylates containing a hydrophilic ester group when the pendant group is both rigid and hydrophobic. This insight will help inform and predict the further development of polymers resistant to bacterial attachment. PMID:25491266

  9. 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.

  10. 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.

  11. 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.

  12. Optimally designed fields for controlling molecular dynamics

    Science.gov (United States)

    Rabitz, Herschel

    1991-10-01

    This research concerns the development of molecular control theory techniques for designing optical fields capable of manipulating molecular dynamic phenomena. Although is has been long recognized that lasers should be capable of manipulating dynamic events, many frustrating years of intuitively driven laboratory studies only serve to illustrate the point that the task is complex and defies intuition. The principal new component in the present research is the recognition that this problem falls into the category of control theory and its inherent complexities require the use of modern control theory tools largely developed in the engineering disciplines. Thus, the research has initiated a transfer of the control theory concepts to the molecular scale. Although much contained effort will be needed to fully develop these concepts, the research in this grant set forth the basic components of the theory and carried out illustrative studies involving the design of optical fields capable of controlling rotational, vibrational and electronic degrees of freedom. Optimal control within the quantum mechanical molecular realm represents a frontier area with many possible ultimate applications. At this stage, the theoretical tools need to be joined with merging laboratory optical pulse shaping capabilities to illustrate the power of the concepts.

  13. 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. PMID:26558887

  14. 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.

  15. 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. PMID:27461341

  16. Molecular Dynamics in Dissociative Electron Attachment to CO probed by Velocity Slice Imaging

    CERN Document Server

    Nag, Pamir

    2014-01-01

    Angular distribution and kinetic energy distribution of O$^-$/CO ions formed by dissociative electron attachment process has been studied for 9, 9.5, 10, 10.5, 11, 11.5 eV incident electron energies using time sliced velocity map imaging spectrometer. The angular distribution of the ions formed with different kinetic energy for same incident electron energy are studied separately. The kinetic energy distribution is energy dependent and a second peak appears after 10.5 eV incident electron energy. We found the existence of two processes leading to the O$^-$ formation, $e^- +\\text{CO}(^1\\Sigma^+) \\rightarrow \\text{CO}^{-*} \\rightarrow \\text{O}^- (^2P) + \\text{C}^* (^3P) $ and $e^- + \\text{CO}(^1\\Sigma^+) \\rightarrow \\text{CO}^{-*} \\rightarrow \\text{O}^- (^2P) + \\text{C}^* (^1D)$. We have investigated the symmetry of intermediate state for different incident electron energies and found the presence of $\\Sigma$ and $\\Pi$ state at 9, 9.5 and 10 eV. At 10.5, 11 and 11.5 eV in the first process $\\Sigma, \\, \\Pi$ and ...

  17. Electron-attachment processes

    International Nuclear Information System (INIS)

    Topics covered include: (1) modes of production of negative ions, (2) techniques for the study of electron attachment processes, (3) dissociative electron attachment to ground-state molecules, (4) dissociative electron attachment to hot molecules (effects of temperature on dissociative electron attachment), (5) molecular parent negative ions, and (6) negative ions formed by ion-pair processes and by collisions of molecules with ground state and Rydberg atoms

  18. 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.

  19. Diverse redox-active molecules bearing O-, S-, or Se-terminated tethers for attachment to silicon in studies of molecular information storage.

    Science.gov (United States)

    Balakumar, Arumugham; Lysenko, Andrey B; Carcel, Carole; Malinovskii, Vladimir L; Gryko, Daniel T; Schweikart, Karl-Heinz; Loewe, Robert S; Yasseri, Amir A; Liu, Zhiming; Bocian, David F; Lindsey, Jonathan S

    2004-03-01

    A molecular approach to information storage employs redox-active molecules tethered to an electroactive surface. Attachment of the molecules to electroactive surfaces requires control over the nature of the tether (linker and surface attachment group). We have synthesized a collection of redox-active molecules bearing different linkers and surface anchor groups in free or protected form (hydroxy, mercapto, S-acetylthio, and Se-acetylseleno) for attachment to surfaces such as silicon, germanium, and gold. The molecules exhibit a number of cationic oxidation states, including one (ferrocene), two [zinc(II)porphyrin], three [cobalt(II)porphyrin], or four (lanthanide triple-decker sandwich compound). Electrochemical studies of monolayers of a variety of the redox-active molecules attached to Si(100) electrodes indicate that molecules exhibit a regular mode of attachment (via a Si-X bond, X = O, S, or Se), relatively homogeneous surface organization, and robust reversible electrochemical behavior. The acetyl protecting group undergoes cleavage during the surface deposition process, enabling attachment to silicon via thio or seleno groups without handling free thiols or selenols. PMID:14986994

  20. A CONCEPTUAL DESIGN OF WIND FRICTION REDUCTION ATTACHMENTS TO THE REAR PORTION OF A CAR FOR BETTER FUEL ECONOMY AT HIGH SPEEDS

    Directory of Open Access Journals (Sweden)

    Dr. G.Jayachandra Reddy

    2012-05-01

    Full Text Available Normally all the car bodies are streamlined for very less wind drag coefficient, but still due to the length of car as constraint the rear portion of the car was not fully streamlined. The present paper objective is to design the wind friction reduction attachments to the rear portion of a car which can be opened and closed depending onthe requirement, thereby mileage of the vehicle at high speeds will be improved and the car can travel at higher speeds without increasing the engine capacity. The rear attachments of car can be closed in traffic and parking periods and when the vehicle is travelling on highways at high speed, the attachments are opened. To open and close the wind friction reduction attachments a hydraulic system is designed. The wind friction reduction attachments are designed to be inside the rear door in the closed condition so that there won’t be any problem in aesthetic point of view.

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

    OpenAIRE

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

    2009-01-01

    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.

  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. 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.

  4. 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...

  5. 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.

  6. Biorefinery: a design tool for molecular gelators.

    Science.gov (United States)

    John, George; Shankar, Balachandran Vijai; Jadhav, Swapnil R; Vemula, Praveen Kumar

    2010-12-01

    Molecular gels, the macroscopic products of a nanoscale bottom-up strategy, have emerged as a promising functional soft material. The prospects of tailoring the architecture of gelator molecules have led to the formation of unique, highly tunable gels for a wide spectrum of applications from medicine to electronics. Biorefinery is a concept that integrates the processes of converting biomass/renewable feedstock and the associated infrastructure used to produce chemicals and materials, which is analogous to petroleum-based refinery. The current review assimilates the successful efforts to demonstrate the prospects of the biorefinery concept for developing new amphiphiles as molecular gelators. Amphiphiles based on naturally available raw materials such as amygdalin, vitamin C, cardanol, arjunolic acid, and trehalose that possess specific functionality were synthesized using biocatalysis and/or chemical synthesis. The hydrogels and organogels obtained from such amphiphiles were conceptually demonstrated for diverse applications including drug-delivery systems and the templated synthesis of hybrid materials. PMID:20465204

  7. Research on the improvement design for the attachment of supports to AP1000 module wall

    International Nuclear Information System (INIS)

    Background: Modularization is one of the main characteristics for AP1000 nuclear power plant building. The steel-concrete-steel module wall is used instead of reinforced concrete structure wall. Usually, lots of Overlay Plate Embedments will be installed on the module wall to connect and fasten other structures, such as pipes, equipment and operation platforms. As for many supports taking less design loads, the safety margin is too big when using OLP embedment. Purpose: An improvement design will make sense that the supports with less design loads can be welded directly to the module wall instead of embedments. Methods: A finite element analysis based on nuclear-related concrete code is carried out. Results: Through analysis, the equations for the allowable design loads of supports to be welded directly to module wall are provided in this paper. Conclusions: The improvement design is proved feasible. In this way, the strength for steel face plate and studs will be utilized fully and this method will facilitate and simplify the design and construction with considerable engineering application value. (authors)

  8. Metal-wool heat shields for space shuttle. [design, fabrication, and attachment to structure

    Science.gov (United States)

    Miller, R. C.; Clure, J. L.

    1974-01-01

    The packaging of metal wool for reusable thermal heat shields applied to aerodynamic and other surfaces for the space shuttle was analyzed and designed, and samples were fabricated and experimentally studied. Parametric trends were prepared for selected configurations. An all-metal thermally efficient, reliable, reusable and producible heat shield system was designed and structurally tested for use on spacecraft aerodynamic surfaces where temperatures do not exceed 810 K. Stainless steel sheet, primarily for structure and secondarily in the transverse plane for thermal expansion, was shown to accommodate thermal expansion in all directions when restrained at the edges and heated to 1360 K. Aerodynamic loads of 0.35 x 1000,000 newtons/sq meter, and higher, may be easily accepted by structures of this design. Seven all-metal thermal protection specimens, 12.7 cm square and 2.5 cm thick were fabricated and are being experimentally evaluated at simulated shuttle entry conditions in an arc jet facility.

  9. 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…

  10. 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...

  11. 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.

  12. 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.

  13. 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...

  14. Product Attachment

    OpenAIRE

    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 the relationship between product attachment and product lifetime. In addition, we studied which determinants may affect the strength of the emotional bond with products and uncovered the role of the ...

  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. 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

    and on the availability of suitable models for property prediction. A new CAMD methodology that addresses this issue by combining molecular modeling techniques with a traditional CAMD approach is presented. The new method includes a new molecular/atomic structure generation algorithm, a large collection of property...... estimation methods, and, a link to molecular modelling tools. Application of the new CAMD method is highlighted through two industrial examples. (C) 1999 Elsevier Science B.V. All rights reserved.......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...

  17. 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.

  18. 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

  19. 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

  20. A computational molecular design framework for crosslinked polymer networks

    OpenAIRE

    Eslick, J.C.; Q. Ye; J. Park; Topp, E.M.; Spencer, P.; Camarda, K.V.

    2008-01-01

    Crosslinked polymers are important in a very wide range of applications including dental restorative materials. However, currently used polymeric materials experience limited durability in the clinical oral environment. Researchers in the dental polymer field have generally used a time-consuming experimental trial-and-error approach to the design of new materials. The application of computational molecular design (CMD) to crosslinked polymer networks has the potential to facilitate developmen...

  1. Lattice enumeration for inverse molecular design using the signature descriptor.

    Science.gov (United States)

    Martin, Shawn

    2012-07-23

    We describe an inverse quantitative structure-activity relationship (QSAR) framework developed for the design of molecular structures with desired properties. This framework uses chemical fragments encoded with a molecular descriptor known as a signature. It solves a system of linear constrained Diophantine equations to reorganize the fragments into novel molecular structures. The method has been previously applied to problems in drug and materials design but has inherent computational limitations due to the necessity of solving the Diophantine constraints. We propose a new approach to overcome these limitations using the Fincke-Pohst algorithm for lattice enumeration. We benchmark the new approach against previous results on LFA-1/ICAM-1 inhibitory peptides, linear homopolymers, and hydrofluoroether foam blowing agents. Software implementing the new approach is available at www.cs.otago.ac.nz/homepages/smartin. PMID:22657105

  2. Molecular docking sites designed for the generation of highly crystalline covalent organic frameworks

    Science.gov (United States)

    Ascherl, Laura; Sick, Torben; Margraf, Johannes T.; Lapidus, Saul H.; Calik, Mona; Hettstedt, Christina; Karaghiosoff, Konstantin; Döblinger, Markus; Clark, Timothy; Chapman, Karena W.; Auras, Florian; Bein, Thomas

    2016-04-01

    Covalent organic frameworks (COFs) formed by connecting multidentate organic building blocks through covalent bonds provide a platform for designing multifunctional porous materials with atomic precision. As they are promising materials for applications in optoelectronics, they would benefit from a maximum degree of long-range order within the framework, which has remained a major challenge. We have developed a synthetic concept to allow consecutive COF sheets to lock in position during crystal growth, and thus minimize the occurrence of stacking faults and dislocations. Hereby, the three-dimensional conformation of propeller-shaped molecular building units was used to generate well-defined periodic docking sites, which guided the attachment of successive building blocks that, in turn, promoted long-range order during COF formation. This approach enables us to achieve a very high crystallinity for a series of COFs that comprise tri- and tetradentate central building blocks. We expect this strategy to be transferable to a broad range of customized COFs.

  3. 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.

  4. 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.

  5. Design of Carborane Molecular Architectures via Electronic Structure Computations

    Directory of Open Access Journals (Sweden)

    Josep M. Oliva

    2009-01-01

    Full Text Available Quantum-mechanical electronic structure computations were employed to explore initial steps towards a comprehensive design of polycarborane architectures through assembly of molecular units. Aspects considered were (i the striking modification of geometrical parameters through substitution, (ii endohedral carboranes and proposed ejection mechanisms for energy/ion/atom/energy storage/transport, (iii the excited state character in single and dimeric molecular units, and (iv higher architectural constructs. A goal of this work is to find optimal architectures where atom/ion/energy/spin transport within carborane superclusters is feasible in order to modernize and improve future photoenergy processes.

  6. 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

  7. 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,

  8. 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.

  9. Designing an university-level module on molecular imaging chemistry

    International Nuclear Information System (INIS)

    training in radiopharmacy both in theory and hands-on practice. Final-year radiology students in Polytechnic have to go through a series of lectures on radiopharmacy and also practicals in hospital radiopharmacy laboratory. But due to the Government's initiatives on biomedical industries and also due to a global trend, interest in bio/medical imaging is rising among scientists and students. There is a need to fulfil this demand by introducing new course or modules at the University level. Designing an university-level module on molecular imaging chemistry: In National University of Singapore, a graduate student (MSc and PhD) level 5 module on ''Medical Imaging'' has already been introduced and a new module on ''Molecular Imaging Chemistry'' will be introduced soon. A module of this kind should serve as a link between chemistry, molecular imaging and clinical application with emphasis on chemical probe design. And should introduce contemporary topics and emerging concepts in chemistry related to molecular imaging. A brief introduction on different modalities of molecular imaging and principles of biomedical imaging should be introduced including principles of medical imaging equipment. How this knowledge will direct the chemical synthesis should be highlighted (lead directed synthesis). There should be a coverage on pharmacology and drug discovery process as imaging probes could be considered as drugs. Here is an example of an outline for such module: - Introduction: - What is molecular imaging? - Why molecular imaging? - What is biomedical imaging? - Different modalities of molecular imaging; - Different types of molecular imaging; - In vitro, ex vivo, in vivo imaging; Drug discovery process; - Pharmacological basis. Molecular Imaging Chemistry: - general construct of imaging probe (molecular reporter system); - Bioimaging factors influencing chemical probe synthesis; Optical imaging probes; - Radioimaging probes; - MR contrast agents; - Probes for other modalities, X ray

  10. 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.

  11. 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. PMID:26986442

  12. 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.

  13. 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.

  14. 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...... 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...... pharmaceutical compound, is addressed. One of the important issues namely, the effect of solvent on the shape of ibuprofen crystals is also considered in the MINLP model. The second case study is a mixture design problem where an optimal solvent/anti-solvent mixture is designed for crystallization of ibuprofen...

  15. 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.

  16. 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...

  17. 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℃.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Molecular Design Basis for Hydrogen Storage in Clathrate Hydrates

    Energy Technology Data Exchange (ETDEWEB)

    John, Vijay T [Tulane University; McPherson, Gary L [Tulane University; Ashbaugh, Hank [Tulane University; Johnes, Camille Y [Columbia University

    2013-06-28

    We attach a final technical report for the project. The report contains the list of all peer reviewed publications that have resulted from the contract. I will be happy to send the pdf files of the papers.

  4. A computational molecular design framework for crosslinked polymer networks.

    Science.gov (United States)

    Eslick, J C; Ye, Q; Park, J; Topp, E M; Spencer, P; Camarda, K V

    2009-05-21

    Crosslinked polymers are important in a very wide range of applications including dental restorative materials. However, currently used polymeric materials experience limited durability in the clinical oral environment. Researchers in the dental polymer field have generally used a time-consuming experimental trial-and-error approach to the design of new materials. The application of computational molecular design (CMD) to crosslinked polymer networks has the potential to facilitate development of improved polymethacrylate dental materials. CMD uses quantitative structure property relations (QSPRs) and optimization techniques to design molecules possessing desired properties. This paper describes a mathematical framework which provides tools necessary for the application of CMD to crosslinked polymer systems. The novel parts of the system include the data structures used, which allow for simple calculation of structural descriptors, and the formulation of the optimization problem. A heuristic optimization method, Tabu Search, is used to determine candidate monomers. Use of a heuristic optimization algorithm makes the system more independent of the types of QSPRs used, and more efficient when applied to combinatorial problems. A software package has been created which provides polymer researchers access to the design framework. A complete example of the methodology is provided for polymethacrylate dental materials. PMID:23904665

  5. 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...

  6. 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

  7. 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.

  8. Rationally designed molecular beacons for bioanalytical and biomedical applications.

    Science.gov (United States)

    Zheng, Jing; Yang, Ronghua; Shi, Muling; Wu, Cuichen; Fang, Xiaohong; Li, Yinhui; Li, Jishan; Tan, Weihong

    2015-05-21

    Nucleic acids hold promise as biomolecules for future applications in biomedicine and biotechnology. Their well-defined structures and compositions afford unique chemical properties and biological functions. Moreover, the specificity of hydrogen-bonded Watson-Crick interactions allows the construction of nucleic acid sequences with multiple functions. In particular, the development of nucleic acid probes as essential molecular engineering tools will make a significant contribution to advancements in biosensing, bioimaging and therapy. The molecular beacon (MB), first conceptualized by Tyagi and Kramer in 1996, is an excellent example of a double-stranded nucleic acid (dsDNA) probe. Although inactive in the absence of a target, dsDNA probes can report the presence of a specific target through hybridization or a specific recognition-triggered change in conformation. MB probes are typically fluorescently labeled oligonucleotides that range from 25 to 35 nucleotides (nt) in length, and their structure can be divided into three components: stem, loop and reporter. The intrinsic merit of MBs depends on predictable design, reproducibility of synthesis, simplicity of modification, and built-in signal transduction. Using resonance energy transfer (RET) for signal transduction, MBs are further endowed with increased sensitivity, rapid response and universality, making them ideal for chemical sensing, environmental monitoring and biological imaging, in contrast to other nucleic acid probes. Furthermore, integrating MBs with targeting ligands or molecular drugs can substantially support their in vivo applications in theranositics. In this review, we survey advances in bioanalytical and biomedical applications of rationally designed MBs, as they have evolved through the collaborative efforts of many researchers. We first discuss improvements to the three components of MBs: stem, loop and reporter. The current applications of MBs in biosensing, bioimaging and therapy will then

  9. 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.

  10. Design strategies for the molecular level synthesis of supported catalysts.

    Science.gov (United States)

    Wegener, Staci L; Marks, Tobin J; Stair, Peter C

    2012-02-21

    Supported catalysts, metal or oxide catalytic centers constructed on an underlying solid phase, are making an increasingly important contribution to heterogeneous catalysis. For example, in industry, supported catalysts are employed in selective oxidation, selective reduction, and polymerization reactions. Supported structures increase the thermal stability, dispersion, and surface area of the catalyst relative to the neat catalytic material. However, structural and mechanistic characterization of these catalysts presents a formidable challenge because traditional preparations typically afford complex mixtures of structures whose individual components cannot be isolated. As a result, the characterization of supported catalysts requires a combination of advanced spectroscopies for their characterization, unlike homogeneous catalysts, which have relatively uniform structures and can often be characterized using standard methods. Moreover, these advanced spectroscopic techniques only provide ensemble averages and therefore do not isolate the catalytic function of individual components within the mixture. New synthetic approaches are required to more controllably tailor supported catalyst structures. In this Account, we review advances in supported catalyst synthesis and characterization developed in our laboratories at Northwestern University. We first present an overview of traditional synthetic methods with a focus on supported vanadium oxide catalysts. We next describe approaches for the design and synthesis of supported polymerization and hydrogenation catalysts, using anchoring techniques which provide molecular catalyst structures with exceptional activity and high percentages of catalytically significant sites. We then highlight similar approaches for preparing supported metal oxide catalysts using atomic layer deposition and organometallic grafting. Throughout this Account, we describe the use of incisive spectroscopic techniques, including high

  11. 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.

  12. 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. PMID:27321920

  13. Molecular and cellular designs of insect taste receptor system

    Directory of Open Access Journals (Sweden)

    Kunio Isono

    2010-06-01

    Full Text Available The insect gustatory receptors (GRs are members of a large G-protein coupled receptor family distantly related to the insect olfactory receptors. They are phylogenetically different from taste receptors of most other animals. GRs are often coexpressed with other GRs in single receptor neurons. Taste receptors other than GRs are also expressed in some neurons. Recent molecular studies in the fruitfly Drosophila revealed that the insect taste receptor system not only covers a wide ligand spectrum of sugars, bitter substances or salts that are common to mammals but also includes reception of pheromone and somatosensory stimulants. However, the central mechanism to perceive and discriminate taste information is not yet elucidated. Analysis of the primary projection of taste neurons to the brain shows that the projection profiles depend basically on the peripheral locations of the neurons as well as the GRs that they express. These results suggest that both peripheral and central design principles of insect taste perception are different from those of olfactory perception.

  14. 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...

  15. 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.

  16. 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…

  17. 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

  18. 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...

  19. 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)

  20. 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.

  1. 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...

  2. 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

  3. 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.

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

    DEFF Research Database (Denmark)

    The objective of this paper is to introduce the new concept of property integration. It is based on tracking and integrating properties throughout the process. This is made possible by exploiting the unique features at the interface of process and molecular design. Recently developed clustering...... 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....

  5. Adult Attachment and Psychotherapy

    OpenAIRE

    Rietzschel, Julia

    2012-01-01

    This thesis explores the association between adult attachment and psychological therapy by examining attachment as an outcome variable of therapy, as well as a predictor of therapy outcome. The literature review systematically explores research that has examined changes in attachment representations during psychological therapy. The purpose of the review is to enhance understanding of change processes in adult attachment and to provide empirical support to the premises of attachment theory. I...

  6. Attachment behavior in rats

    OpenAIRE

    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 there is a relationship between specific types of insecure attachment and specific types of psychiatric disorders. Next, a reinterpretation of the literature on social preference experiments in rodent...

  7. 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.

  8. Recent advances in the molecular design of synthetic vaccines

    Science.gov (United States)

    Jones, Lyn H.

    2015-12-01

    Vaccines have typically been prepared using whole organisms. These are normally either attenuated bacteria or viruses that are live but have been altered to reduce their virulence, or pathogens that have been inactivated and effectively killed through exposure to heat or formaldehyde. However, using whole organisms to elicit an immune response introduces the potential for infections arising from a reversion to a virulent form in live pathogens, unproductive reactions to vaccine components or batch-to-batch variability. Synthetic vaccines, in which a molecular antigen is conjugated to a carrier protein, offer the opportunity to circumvent these problems. This Perspective will highlight the progress that has been achieved in developing synthetic vaccines using a variety of molecular antigens. In particular, the different approaches used to develop conjugate vaccines using peptide/proteins, carbohydrates and other small molecule haptens as antigens are compared.

  9. 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

  10. Characterization-Based Molecular Design of Bio-Fuel Additives Using Chemometric and Property Clustering Techniques

    OpenAIRE

    Subin eHada; Charles Conrad Solvason; Mario Richard Eden

    2014-01-01

    In this work, multivariate characterization data such as infrared spectroscopy was used as a source of descriptor data involving information on molecular architecture for designing structured molecules with tailored properties. Application of multivariate statistical techniques such as principal component analysis allowed capturing important features of the molecular architecture from enormous amount of complex data to build appropriate latent variable models. Combining the property clusterin...

  11. 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.

  12. 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.

  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. 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.

  15. Development of Lathe Attachment for a CNC Machine

    Science.gov (United States)

    Roy, V.; Kumar, S.

    2013-04-01

    A lathe attachment has been developed for an existing CNC machine (installed with rapid prototyping attachment) using conceptual design. The CNC machine operates on mechatronic controls and a computer interface called CAMSOFT, and is used as a CNC Lathe after installing the respective attachment to it. The conceptual design phase, starts from an idea and different components of the lathe are designed as attachment using CAD modelling and is followed by fabrication phase. The lathe attachment is successfully developed and is installed to the CNC machine. The working of the CNC Lathe attachment is checked by making some machining operation like turning and thread cutting. The machining operations are successfully done. The CNC machine becomes multifunctional with the presently developed lathe attachment and the existing RP (rapid prototyping) attachment, and can be used accordingly by installing the respective attachment to it. The CNC machine is useful for carrying research work in both the fields, when installed with the appropriate attachment.

  16. 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.

  17. 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....

  18. 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....

  19. Molecular Designs for Enhancement of Polarity in Ferroelectric Soft Materials

    Science.gov (United States)

    Ohtani, Ryo; Nakaya, Manabu; Ohmagari, Hitomi; Nakamura, Masaaki; Ohta, Kazuchika; Lindoy, Leonard F.; Hayami, Shinya

    2015-11-01

    The racemic oxovanadium(IV) salmmen complexes, [VO((rac)-(4-X-salmmen))] (X = C12C10C5 (1), C16 (2), and C18 (3); salmmen = N,N‧-monomethylenebis-salicylideneimine) with “banana shaped” molecular structures were synthesized, and their ferroelectric properties were investigated. These complexes exhibit well-defined hysteresis loops in their viscous phases, moreover, 1 also displays liquid crystal behaviour. We observed a synergetic effect influenced by three structural aspects; the methyl substituents on the ethylene backbone, the banana shaped structure and the square pyramidal metal cores all play an important role in generating the observed ferroelectricity, pointing the way to a useful strategy for the creation of advanced ferroelectric soft materials.

  20. 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...

  1. Molecular Design for Tuning Work Functions of Transparent Conducting Electrodes.

    Science.gov (United States)

    Koldemir, Unsal; Braid, Jennifer L; Morgenstern, Amanda; Eberhart, Mark; Collins, Reuben T; Olson, Dana C; Sellinger, Alan

    2015-06-18

    In this Perspective, we provide a brief background on the use of aromatic phosphonic acid modifiers for tuning work functions of transparent conducting oxides, for example, zinc oxide (ZnO) and indium tin oxide (ITO). We then introduce our preliminary results in this area using conjugated phosphonic acid molecules, having a substantially larger range of dipole moments than their unconjugated analogues, leading to the tuning of ZnO and ITO electrodes over a 2 eV range as derived from Kelvin probe measurements. We have found that these work function changes are directly correlated to the magnitude and the direction of the computationally derived molecular dipole of the conjugated phosphonic acids, leading to the predictive power of computation to drive the synthesis of new and improved phosphonic acid ligands. PMID:26266603

  2. 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.

  3. Attachment Without Fear

    OpenAIRE

    Bell, David C.

    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...

  4. Special Attachments. Module 19.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special attachments, one in a series dealing with industrial sewing machines, their attachments, and operation, covers four topics: gauges; cording attachment; zipper foot; and hemming, shirring, and binding. For each topic these components are provided: an introduction, directions, an objective, learning activities, student…

  5. Precision Attachment: Retained Overdenture

    OpenAIRE

    Jayasree, K; Mrs.M.Bharathi; Nag, V. Dileep; B. Vinod

    2011-01-01

    Precision attachments are small interlocking devices to connect prosthesis and abutments that offer a variety of solutions to the challenge of balance between functional stability and cosmetic appeal. Precision attachments have wide applications, used in fixed removable bridge, removable partial dentures, overdentures, implant retained overdentures, and maxillofacial prosthesis. Attachment retained overdentures helps in distribution of masticatory forces, minimizes trauma to abutments and sof...

  6. 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.

  7. 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...

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

    DEFF Research Database (Denmark)

    . 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...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    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.......Today's society needs many chemical-based products for its survival, nutrition, health, transportation, agriculture, and the functioning of processes. Chemical-based products have to be designed/developed in order to meet these needs, while at the same time, they must be innovative and sustainable...

  10. Attachment fixation of the overdenture: part II.

    Science.gov (United States)

    Mensor, M C

    1978-01-01

    Many attachment systems of the bar or stud type increase the stability of an overdenture. When selecting an attachment it is essential to consider the skill of the dentist-laboratory team as well as the dexterity of the patient and to use the easiest system that will still improve stabilization. Generally simplicity in design, ease of maintenance, and minimum leverage should be paramount considerations in selection. Use of a guide such as the EM Gauge and of the EM Attachment Selector significantly reduces the confusion in selecting attachments and increases the working armamentarium for stabilizing an overdenture. PMID:340660

  11. Design of molecularly imprinted polymers for sensors and solid phase extraction

    OpenAIRE

    Subrahmanyam, Sreenath

    2002-01-01

    This thesis presents broadly the applications of molecularly imprinted polymers in sensors and solid phase extraction. Sensors for creatine and creatinine have been reported using a novel method of rational design of molecularly imprinted polymers (MIPs), and solid phase extraction of aflatoxin-B 1 has also been described in the thesis. A method for the selective detection of creataine and creatinine is reported in this thesis, which is based on the reaction between polymeri...

  12. 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.

  13. 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.

  14. 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.

  15. 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....

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Oxytocin enhances the experience of attachment security

    Science.gov (United States)

    Buchheim, Anna; Heinrichs, Markus; George, Carol; Pokorny, Dan; Koops, Eva; Henningsen, Peter; O’Connor, Mary-Frances; Gundel, Harald

    2011-01-01

    Summary Repeated interactions between infant and caregiver result in either secure or insecure relationship attachment patterns, and insecure attachment may affect individual emotion-regulation and health. Given that oxytocin enhances social approach behavior in animals and humans, we hypothesized that oxytocin might also promote the experience of attachment security in humans. Within a 3-week interval 26 healthy male students classified with an insecure attachment pattern were invited twice to an experimental session. Within each session, a single dose of oxytocin or placebo was administered, using a double-blind, placebo-controlled within-subject design. In both conditions, subjects completed an attachment task based on the Adult Attachment Projective Picture System (AAP). Thirty-two AAP picture system presentations depicted attachment-related events (e.g. illness, solitude, separation, loss), and were each accompanied by four prototypical phrases representing one secure and three insecure attachment categories. In the oxytocin condition, a significant proportion of these insecure subjects (N = 18; 69%) changed their rankings of “secure attachment” phrases towards the more appropriate for the AAP picture presentation, and the same subjects decreased in overall rating of the “insecure attachment” phrases. In particular, there was a significant decrease in the number of subjects ranking the pictures with “insecure-preoccupied” phrases from the placebo to the oxytocin condition. We find that a single dose of intranasally administered oxytocin is sufficient to induce a significant increase in the experience of attachment security in adults classified previously as insecure. PMID:19457618

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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. PMID:27390530

  8. Optimization Design of Attached Reducer of Orchard Ditching’ s Tractor%果园开沟作业机组附加减速器的优化设计

    Institute of Scientific and Technical Information of China (English)

    柴立发; 刘俊峰; 李建平

    2014-01-01

    果园开沟作业需要拖拉机配有爬行挡,在满足工作和农艺要求下,机组速度应控制在120~140 m/h。为此,通过对开沟机减速器与机组附加减速器的组合传动系统设计,实现了在果园正常开沟作业。以机组附加减速器为研究重点,采用MatLab 软件的全局优化算法,对机组附加减速器的设计变量和约束条件进行了研究,并建立了优化数学模型。经过MatLab 优化设计后,机组附加减速器的总中心距比传统理论设计总中心距减少了15%。%The tractor need to be equipped with creeper gear when trenching in the orchard , the speed of tractor should be controlled in 120 ~140 m/h to satisfied work and agronomic requirements .Our group realized the normal trenching work in orchard by designing the combination drive system between reducer of trencher and attached reducer of tractor .To set attached reducer as the research focus , the paper uses the optimization algorithm of Matlab software to have a study on the design variables and constraints of the attached gear reducer , and the optimization mathematical model is established . Through optimization of Matlab , the center distance of attached gear reducer have decreased by 15%than traditional the-oretical design ’ s.

  9. 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…

  10. Design and Application of Self-Assembled Low Molecular Weight Hydrogels

    NARCIS (Netherlands)

    Loos, Maaike de; Esch, Jan H. van; Feringa, Bernard

    2005-01-01

    Over the past years, the gelation of aqueous solutions by low molecular weight (LMW) compounds has become an area of increasing interest, owing to developments in the field of LMW organogelators. Until recently, LMW hydrogelators were found only by serendipity, nowadays rational design as well as ap

  11. Design and application of self-assembled low molecular weight hydrogels

    NARCIS (Netherlands)

    de Loos, M.; Feringa, B.L.; van Esch, J.

    2005-01-01

    Over the past years, the gelation of aqueous solutions by low molecular weight (LMW) compounds has become an area of increasing interest, owing to developments in the field of LMW organogelators. Until recently, LMW hydrogelators were found only by serendipity, nowadays rational design as well as ap

  12. Web based learning support for experimental design in molecular biology: a top-down approach

    NARCIS (Netherlands)

    Aegerter-Wilmsen, T.; Hartog, R.; Bisseling, T.

    2003-01-01

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

  13. 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…

  14. Attachment and Early Maltreatment.

    Science.gov (United States)

    Egeland, Byron; Sroufe, L. Alan

    1981-01-01

    Attachment outcomes of 31 maltreatment cases (involving extreme neglect or abuse), selected from a total poverty sample of 267 high-risk mothers and their children, were compared to those of a subsample of 33 cases with a history of excellent care. Attachment was assessed when infants were 12 and 18 months old. (Author/MP)

  15. 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...

  16. 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.

  17. 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.

  18. 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. PMID:26883005

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

    DEFF Research Database (Denmark)

    Zhang, Lei; Cignitti, Stefano; Gani, Rafiqul

    higher level analysis of the molecular structure and the final selection of the product. Samudra and Sahinidis [4] proposed a new optimization model using relaxed property targets and refined property targets with structural corrections. It is usually difficult to model and solve the MILP/MINLP problem...... developed for the consideration of higher order groups in the molecular generation step of CAMD through mathematical optimization [5]. The model can consider both first and second order groups simultaneously in the MILP/MINLP formulation through a set of mathematical constraints. Structural constraints...... applicability will be demonstrated through the solution of a range of product design problems from literature, such as design of simple molecules (solvents and refrigerants) to design of complex molecules (polymers, lipids and surfactants)....

  20. 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.

  1. Characterization-Based Molecular Design of Biofuel Additives Using Chemometric and Property Clustering Techniques

    Directory of Open Access Journals (Sweden)

    Subin eHada

    2014-06-01

    Full Text Available In this work, multivariate characterization data such as infrared (IR spectroscopy was used as a source of descriptor data involving information on molecular architecture for designing structured molecules with tailored properties. Application of multivariate statistical techniques such as principal component analysis (PCA allowed capturing important features of the molecular architecture from complex data to build appropriate latent variable models. Combining the property clustering techniques and group contribution methods (GCM based on characterization data in a reverse problem formulation enabled identifying candidate components by combining or mixing molecular fragments until the resulting properties match the targets. The developed methodology is demonstrated using molecular design of biodiesel additive which when mixed with off-spec biodiesel produces biodiesel that meets the desired fuel specifications. The contribution of this work is that the complex structures and orientations of the molecule can be included in the design, thereby allowing enumeration of all feasible candidate molecules that matched the identified target but were not part of original training set of molecules.

  2. 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.

  3. 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.

  4. 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.

  5. Design of a molecular beam surface scattering apparatus for velocity and angular distribution measurements

    Energy Technology Data Exchange (ETDEWEB)

    Ceyer, S.T.; Siekhaus, W.J.; Somorjai, G.A.

    1981-09-01

    A molecular beam surface scattering apparatus designed for the study of corrosion and catalytic surface reactions is described. The apparatus incorporates two molecular or atomic beams aimed at a surface characterized by low energy electron diffraction (LEED) and Auger electron spectroscopy (AES), a rotatable, differentially pumped quadrupole mass spectrometer, and a versatile manipulator. Angular distributions and energy distributions as a function of angle and independent of the surface residence time can be measured. Typical data for the oxidation of deuterium to D/sub 2/O on a Pt(111) crystal surface are presented.

  6. DESIGN OF A MOLECULAR BEAM SURFACE SCATTERING APPARATUS FOR VELOCITY AND ANGULAR DISTRIBUTION MEASUREMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Ceyer, S. T.; Siekhaus, W. J.; Somorjai, G. A.

    1980-11-01

    A molecular beam surface scattering apparatus designed for the study of corrosion and catalyticsurfacereactions is described. The apparatus incorporates two molecular or atomic beams aimed at a surface characterized by low energy electron diffraction (LEED) and Auger electron spectroscopy (AES), a rotatable, differentially pumped quadrupole mass spectrometer, and a versatile manipulator. Angular distributions and energy distributions as a funcion of angle and independent of the surface residence time can be measured. Typical data for the oxidation of deuterium to D{sub 2}O on a Pt(lll) crystal surface are presented.

  7. Environmental and genetic influences on early attachment.

    Science.gov (United States)

    Gervai, Judit

    2009-01-01

    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. PMID:19732441

  8. 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.

  9. 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.

  10. 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

  11. Amphiphilic, hydrophilic, or hydrophobic synthetic bacteriochlorins in biohybrid light-harvesting architectures: consideration of molecular designs.

    Science.gov (United States)

    Jiang, Jianbing; Reddy, Kanumuri Ramesh; Pavan, M Phani; Lubian, Elisa; Harris, Michelle A; Jiao, Jieying; Niedzwiedzki, Dariusz M; Kirmaier, Christine; Parkes-Loach, Pamela S; Loach, Paul A; Bocian, David F; Holten, Dewey; Lindsey, Jonathan S

    2014-11-01

    Biohybrid light-harvesting architectures can be constructed that employ native-like bacterial photosynthetic antenna peptides as a scaffold to which synthetic chromophores are attached to augment overall spectral coverage. Synthetic bacteriochlorins are attractive to enhance capture of solar radiation in the photon-rich near-infrared spectral region. The effect of the polarity of the bacteriochlorin substituents on the antenna self-assembly process was explored by the preparation of a bacteriochlorin-peptide conjugate using a synthetic amphiphilic bacteriochlorin (B1) to complement prior studies using hydrophilic (B2, four carboxylic acids) or hydrophobic (B3) bacteriochlorins. The amphiphilic bioconjugatable bacteriochlorin B1 with a polar ammonium-terminated tail was synthesized by sequential Pd-mediated reactions of a 3,13-dibromo-5-methoxybacteriochlorin. Each bacteriochlorin bears a maleimido-terminated tether for attachment to a cysteine-containing analog of the Rhodobacter sphaeroides antenna β-peptide to give conjugates β-B1, β-B2, and β-B3. Given the hydrophobic nature of the β-peptide, the polarity of B1 and B2 facilitated purification of the respective conjugate compared to the hydrophobic B3. Bacteriochlorophyll a (BChl a) associates with each conjugate in aqueous micellar media to form a dyad containing two β-peptides, two covalently attached synthetic bacteriochlorins, and a datively bonded BChl-a pair, albeit to a limited extent for β-B2. The reversible assembly/disassembly of dyad (β-B2/BChl)2 was examined in aqueous detergent (octyl glucoside) solution by temperature variation (15-35 °C). The energy-transfer efficiency from the synthetic bacteriochlorin to the BChl-a dimer was found to be 0.85 for (β-B1/BChl)2, 0.40 for (β-B2/BChl)2, and 0.85 for (β-B3/BChl)2. Thus, in terms of handling, assembly and energy-transfer efficiency taken together, the amphiphilic design examined herein is more attractive than the prior hydrophilic or

  12. 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.

  13. 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.

  14. Examinations on retention of overdentures with elastic frictional attachments

    OpenAIRE

    W. Chladek; G. Chladek; M. Wrzuś-Wieliński; J. Żmudzki

    2010-01-01

    frictional attachments.Design/methodology/approach: The examinations of retention characteristics of traditional attachments, elastic frictional attachments and models of overdentures have been carried out using Zwick testing machine. Retention forces and work essential for separating the attachments have been determined as well. Next the force – displacement characteristics for overdenture model have been registered for two places where the force was applied and for three inclination angles ...

  15. Attachment and Psychotherapy

    OpenAIRE

    McKay, J.M.

    2010-01-01

    The aim of this study was to explore the relationship between therapy outcome, the therapeutic alliance and both patient and therapist attachment styles. 14 therapists and 27 patients participated. 78.57% (n = 11) therapists and 29.63% (n = 8) patients were classified as securely attached by self-report measures. It was predicted that more patients of secure therapists would show clinically significant improvement as determined by CORE-OM scores. However, 21.05% of patients with a secure atta...

  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. 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.

  18. 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

  19. From Computational Photobiology to the Design of Vibrationally Coherent Molecular Devices and Motors

    Science.gov (United States)

    Olivucci, Massimo

    2014-03-01

    In the past multi-configurational quantum chemical computations coupled with molecular mechanics force fields have been employed to investigate spectroscopic, thermal and photochemical properties of visual pigments. Here we show how the same computational technology can nowadays be used to design, characterize and ultimately, prepare light-driven molecular switches which mimics the photophysics of the visual pigment bovine rhodopsin (Rh). When embedded in the protein cavity the chromophore of Rh undergoes an ultrafast and coherent photoisomerization. In order to design a synthetic chromophore displaying similar properties in common solvents, we recently focused on indanylidene-pyrroline (NAIP) systems. We found that these systems display light-induced ground state coherent vibrational motion similar to the one detected in Rh. Semi-classical trajectories provide a mechanistic description of the structural changes associated to the observed coherent motion which is shown to be ultimately due to periodic changes in the π-conjugation.

  20. Multi-objective molecular de novo design by adaptive fragment prioritization.

    Science.gov (United States)

    Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

    2014-04-14

    We present the development and application of a computational molecular de novo design method for obtaining bioactive compounds with desired on- and off-target binding. The approach translates the nature-inspired concept of ant colony optimization to combinatorial building block selection. By relying on publicly available structure-activity data, we developed a predictive quantitative polypharmacology model for 640 human drug targets. By taking reductive amination as an example of a privileged reaction, we obtained novel subtype-selective and multitarget-modulating dopamine D4 antagonists, as well as ligands selective for the sigma-1 receptor with accurately predicted affinities. The nanomolar potencies of the hits obtained, their high ligand efficiencies, and an overall success rate of 90 % demonstrate that this ligand-based computer-aided molecular design method may guide target-focused combinatorial chemistry. PMID:24623390

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Ramlan, Effirul Ikhwan; Zauner, Klaus-Peter

    2013-01-01

    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. PMID:23647621

  12. 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. PMID:27507101

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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. PMID:27366935

  20. 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.

  1. Design Through Simulation of a Molecular Sieve Column for Treatment of MON-3

    Science.gov (United States)

    Swartz, A. Ben; Wilson, D. B.

    1999-01-01

    The presence of water in propellant-grade MON-3 is a concern in the Aerospace Industry. NASA Johnson Space Center (JSC), White Sands Test Facility (WSTF) Propulsion Department has evaluated many types of molecular sieves for control of iron, the corrosion product of water in Mixed Oxides of Nitrogen (MON-3). In 1995, WSTF initiated laboratory and pilot-scale testing of molecular sieve type 3A for removal of water and iron. These tests showed sufficient promise that a series of continuous recycle tests were conducted at WSTF. Periodic samples of the circulating MON-3 solution were analyzed for water (wt %) and iron (ppm, wt). This test column was modeled as a series of transfer units; i. e., each unit represented the height equivalent of a theoretical plate. Such a model assumes there is equilibrium between the adsorbent material and the effluent stream from the unit. Operational and design parameters were derived based on the simulation results. These parameters were used to predict the design characteristics of a proposed molecular sieve column for removal of water and iron from MON-3 at the NASA Kennedy Space Center (KSC). In addition, these parameters were used to simulate a small, single-pass operation column at KSC currently used for treating MON-3. The results of this work indicated that molecular sieve type 3A in 1/16 in. diameter pellets, in a column 2.5 ft. in diameter, 18 ft. in height, and operated at 25 gpm is adequate for the required removal of water and iron from MON-3.

  2. 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)

  3. MOWER ATTACHMENT NOISE

    OpenAIRE

    Mosdzianowski, G.

    1990-01-01

    The noise produced by grass mowing attachments fitted to small tractors and combining a number of rotary blades with a total cutting width of up to 120 cm was investigated. The paper develops a noise reduction concept based on an analysis of sound sources.

  4. 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…

  5. 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.

  6. 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,…

  7. 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.

  8. Design and Strength Analysis of Rife Muzzle Attachment Using Screw Connection%螺纹型式自动步枪膛口装置接口设计及强度分析

    Institute of Scientific and Technical Information of China (English)

    袁点; 马迎辉; 王利萍

    2016-01-01

    对比研究了国内外自动步枪膛口装置的接口型式,概述了目前国内步枪膛口装置接口型式存在的不足。重点针对国内自动步枪膛口装置与枪管销接型式连接强度不足的情况进行了详细分析,设计了采用螺纹型式的自动步枪膛口装置接口,并分别用理论计算和有限元仿真两种方法对螺纹接口的连接强度进行了分析计算。计算和仿真结果表明膛口结构采用螺纹连接后强度满足设计要求。%The rife connection types at home and abroad were compared and studied , and the defects of domestic rife muzzle attachment’s connection type were summarized .After the reasons for the strength shortages of the domestic rife muzzle attachment ’s pin connection were analyzed ,a screw connection type for muzzle attachment was put forward ,and the strength of the screw connection was analyzed by using theoretical arithmetic and FEM analysis .The study results show that the strength of improved muzzle attachment using screw connection can meet the design requirement .

  9. Structural Correspondence of the Oriented Attachment Growth Mechanism of Crystals of the Pharmaceutical Dirithromycin.

    Science.gov (United States)

    Liang, Zuozhong; Wang, Yuan; Wang, Wei; Han, Xianglong; Chen, Jian-Feng; Xue, Chunyu; Zhao, Hong

    2015-12-29

    The oriented attachment (OA) mechanism is promising for designing novel nanomaterials, yet an intensive understanding of the relationship between the crystal structure and attachment orientation is still lacking. In this work, we report layered hexagonal crystals of the pharmaceutical dirithromycin (DIR) containing multiple layers fabricated via a solvothermal method for a certain period of time at 40 °C. These elongated hexagonal crystals experience an OA that is preferentially on the face (001) of the initial crystals to assemble the final crystals into layered stacks. Through agreement with molecular modeling calculations, we predicted the final crystal growth morphology and confirmed the favored attachment surface based on the energy change ΔE following an OA event. These simulation results at the molecular level yielded good agreement with the crystal growth experiments. This study demonstrates the critical importance of combining experiments with a computational approach to understand the intrinsic molecular details of the OA growth mechanism of other compounds and to design nanomaterials with a desirable morphology and physical and chemical properties. PMID:26632998

  10. 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...... 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...... tags facilitate the application and provide the students to articulate knowledge through different modes; images, gestures, and 3D objects...

  11. Molecular design of luminescent Eu(III) complexes as lanthanide lasing material and their optical properties

    International Nuclear Information System (INIS)

    Luminescent polymer (PMMA) containing a Eu(III) complex with a fast radiation rate and a high luminescence quantum efficiency (75 ± 5%) (bis-triphenylphosphineoxide)(tris-hexafluoroacetylacetonato)europium(III) (Eu(hfa)3(TPPO)2), was fabricated. The quantum yield and the radiation rate of the luminescent polymer were found to be 75 ± 5% and 1.1 x 103 s-1, respectively. An Eu(III) complex-doped polymer thin-film was also prepared by use of polyphenylsilsesquioxane (PPSQ) to construct a waveguide lanthanide laser. We propose a strategy for the molecular design of luminescent Eu(III) complexes aiming at lanthanide lasing

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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. PMID:27444189

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Oxytetracycline recovery from aqueous media using computationally designed molecularly imprinted polymers.

    Science.gov (United States)

    Rodríguez-Dorado, Rosalía; Carro, Antonia M; Chianella, Iva; Karim, Kal; Concheiro, Angel; Lorenzo, Rosa A; Piletsky, Sergey; Alvarez-Lorenzo, Carmen

    2016-09-01

    Polymers for recovery/removal of the antimicrobial agent oxytetracycline (OTC) from aqueous media were developed with use of computational design and molecular imprinting. 2-Hydroxyethyl methacrylate, 2-acrylamide-2-methylpropane sulfonic acid (AMPS), and mixtures of the two were chosen according to their predicted affinity for OTC and evaluated as functional monomers in molecularly imprinted polymers and nonimprinted polymers. Two levels of AMPS were tested. After bulk polymerization, the polymers were crushed into particles (200-1000 μm). Pressurized liquid extraction was implemented for template removal with a low amount of methanol (less than 20 mL in each extraction) and a few extractions (12-18 for each polymer) in a short period (20 min per extraction). Particle size distribution, microporous structure, and capacity to rebind OTC from aqueous media were evaluated. Adsorption isotherms obtained from OTC solutions (30-110 mg L(-1)) revealed that the polymers prepared with AMPS had the highest affinity for OTC. The uptake capacity depended on the ionic strength as follows: purified water > saline solution (0.9 % NaCl) > seawater (3.5 % NaCl). Polymer particles containing AMPS as a functional monomer showed a remarkable ability to clean water contaminated with OTC. The usefulness of the stationary phase developed for molecularly imprinted solid-phase extraction was also demonstrated. Graphical Abstract Selection of functional monomers by molecular modeling renders polymer networks suitable for removal of pollutants from contaminated aqueous environments, under either dynamic or static conditions. PMID:27488280

  4. Epitope engineering and molecular metrics of immunogenicity: a computational approach to VLP-based vaccine design.

    Science.gov (United States)

    Joshi, Harshad; Lewis, Kristen; Singharoy, Abhishek; Ortoleva, Peter J

    2013-10-01

    Developing antiviral vaccines is increasingly challenging due to associated time and cost of production as well as emerging drug-resistant strains. A computer-aided vaccine design strategy is presented that could greatly accelerate the discovery process and yield vaccines with high immunogenicity and thermal stability. Our strategy is based on foreign viral epitopes engineered onto well-established virus-like particles (VLPs) and demonstrates that such constructs present similar affinity for antibodies as does a native virus. This binding affinity serves as one molecular metric of immunogenicity. As a demonstration, we engineered a preS1 epitope of hepatitis B virus (HBV) onto the EF loop of human papillomavirus VLP (HPV-VLP). HBV-associated HzKR127 antibody displayed binding affinity for this structure at distances and strengths similar to those for the complex of the antibody with the full HBV (PDBID: 2EH8). This antibody binding affinity assessment, along with other molecular immunogenicity metrics, could be a key component of a computer-aided vaccine design strategy. PMID:23933338

  5. 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.

  6. Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein.

    Directory of Open Access Journals (Sweden)

    Serena Leone

    Full Text Available MNEI is a single chain derivative of monellin, a plant protein that can interact with the human sweet taste receptor, being therefore perceived as sweet. This unusual physiological activity makes MNEI a potential template for the design of new sugar replacers for the food and beverage industry. Unfortunately, applications of MNEI have been so far limited by its intrinsic sensitivity to some pH and temperature conditions, which could occur in industrial processes. Changes in physical parameters can, in fact, lead to irreversible protein denaturation, as well as aggregation and precipitation. It has been previously shown that the correlation between pH and stability in MNEI derives from the presence of a single glutamic residue in a hydrophobic pocket of the protein. We have used molecular dynamics to study the consequences, at the atomic level, of the protonation state of such residue and have identified the network of intramolecular interactions responsible for MNEI stability at acidic pH. Based on this information, we have designed a pH-independent, stabilized mutant of MNEI and confirmed its increased stability by both molecular modeling and experimental techniques.

  7. 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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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 PO43− 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 PO43− 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

  10. 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.

  11. 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

  12. 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.

  13. Picturing Urban Green Attachments

    DEFF Research Database (Denmark)

    Blok, Anders; Meilvang, Marie Leth

    2015-01-01

    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...... 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...... of urban politics as inclusive learning processes, more hospitable to a wider diversity of familiar attachments to cities and their ecologies....

  14. Turbine nozzle attachment system

    Science.gov (United States)

    Norton, Paul F.; Shaffer, James E.

    1995-01-01

    A nozzle guide vane assembly having a preestablished rate of thermal expansion is positioned in a gas turbine engine and being attached to conventional metallic components. The nozzle guide vane assembly includes a pair of legs extending radially outwardly from an outer shroud and a pair of mounting legs extending radially inwardly from an inner shroud. Each of the pair of legs and mounting legs have a pair of holes therein. A plurality of members attached to the gas turbine engine have a plurality of bores therein which axially align with corresponding ones of the pair of holes in the legs. A plurality of pins are positioned within the corresponding holes and bores radially positioning the nozzle guide vane assembly about a central axis of the gas turbine engine.

  15. Universally Rigid Framework Attachments

    CERN Document Server

    Ratmanski, Kiril

    2010-01-01

    A framework is a graph and a map from its vertices to R^d. A framework is called universally rigid if there is no other framework with the same graph and edge lengths in R^d' for any d'. A framework attachment is a framework constructed by joining two frameworks on a subset of vertices. We consider an attachment of two universally rigid frameworks that are in general position in R^d. We show that the number of vertices in the overlap between the two frameworks must be sufficiently large in order for the attachment to remain universally rigid. Furthermore, it is shown that universal rigidity of such frameworks is preserved even after removing certain edges. Given positive semidefinite stress matrices for each of the two initial frameworks, we analytically derive the PSD stress matrices for the combined and edge-reduced frameworks. One of the benefits of the results is that they provide a general method for generating new universally rigid frameworks.

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

    OpenAIRE

    Juen Florian; Arnold Lisa; Meissner Dominik; Nolte Tobias; Buchheim Anna

    2013-01-01

    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 Attach...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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. PMID:27524303

  2. Remedial action and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Attachment 2, Geology report: Appendix B, Preliminary final

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    Detailed investigations of geologic, geomorphic, and seismic conditions at the Burro Canyon site were conducted by the US Department of Energy (DOE) as a disposal site for the tailings at two processing sites near the Slick Rock, Colorado, post office. The purposes of these studies are basic site characterization and identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies (e.g., 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-km radius of the site, provided the basis for seismic design parameters.

  3. Attachment as an Organizational Construct

    Science.gov (United States)

    Sroufe, L. Alan; Waters, Everett

    1977-01-01

    Discusses the conflict between situational influences and stable individual differences in attachment behavior and attempts to resolve this conflict by examining the functions, outcomes, and context sensitivity of attachment behavior and the underlying behavioral control systems that organize it. (JMB)

  4. A comparison of stress distribution and flexion among various designs of bar attachments for implant overdentures: A three dimensional finite element analysis

    OpenAIRE

    Prakash Vijay; D′Souza Mariette; Adhikari Raviraj

    2009-01-01

    Context: Bar overdentures are popular choices among clinicians worldwide but configurations that provide an optimal biomechanical distribution of stress are still debatable. Aims: To compare the stresses and elastic flexion between implant supported bar overdentures in various configurations using finite element analysis. Settings and Design: A CAT scan of a human mandible was used to generate an anatomically accurate mechanical model. Materials and Methods: Three models with bars an...

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

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    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...

  6. 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…

  7. Attachment Behaviors in Autistic Children.

    Science.gov (United States)

    Sigman, Marian; Ungerer, Judy A.

    1984-01-01

    Observation of 14 autistic and 14 nonautistic children of equivalent mental age revealed that autistic Ss showed evidence of attachment to their mothers. Among autistic Ss, those showing increased attachment behaviors in response to separation and reunion demonstrated more advanced symbolic play skills than those showing no attachment change.…

  8. 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…

  9. 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.

  10. 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

    International Nuclear Information System (INIS)

    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 (yd3) (2.1 million cubic meters [m3]) of tailings. The former mill processing area is on the north side of the site and contains 20,000 yd3 (15,000 m3) 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 yd3 (420,000 m3). The total volume of contaminated materials to be disposed of as part of the remedial action is estimated to be 3.37 million yd3 (2.58 million m3). 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

    International Nuclear Information System (INIS)

    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

  16. Molecular Designs and Properties of Highly Efficient Blue Emitters for OLEDs

    Institute of Scientific and Technical Information of China (English)

    Wong Ken-Tsung

    2004-01-01

    Advances made in the molecular design of modern optoelectronic materials have made significant contributions toward the development of organic electronics. The organic light-emitting devices (OLEDs) employing monodisperse or polymeric conjugated materials possess the most promising prospects. However, materials suitable for long-term use as blue light emitters are still far from optimization in terms of stability.In the past few years, interesting materials based on 9,9-diaryl-substituted fluorene as a core structure have been developed in our laboratory. We developed a series of efficient and morphologically stable pyrimidine-containing 9,9'-spirobifluorene-cored oligoaryls as pure blue emitters. The steric hindrance inherent with the molecular structure renders the material with a record-high thin-film PL quantum yield of ~95% and a glass transition temperature (Tg) of ~200 ℃.Blue OLEDs employing this thermally stable compound as the emitting host exhibit unusual endurance for high currents. Injection current over 5,000 mA/cm2 and maximal brightness of~80,000 cd/m2 had been demonstrated, representing the highest values reported for blue OLEDs under dc driving. In addition, a series of oligofluorene homologues have been synthesized. These oligofluorenes exhibit interesting reversible bipolar redox properties and excellent morphological and thermal stability. Furthermore, nondispersive ambipolar high hole and electron mobilities over 10-3 cm2/V.s can be achieved with these oligo(9,9-diarylfluorene)s. In particular, the electron mobility observed represents the highest ever reported for amorphous molecular solids. These intriguing properties together with the high quantum yields in thin films make these oligo(9,9-diarylfluorene)s are promising for OLEDs applications as efficient blue emitters. In this meeting, the synthesis and properties of these materials and their highly efficient OLEDs device characteristics will be discussed.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Design and growth of a P N diode by molecular beam epitaxy

    International Nuclear Information System (INIS)

    In this work, design, growth and characterization of a GaAs p-n contact is presented. The contact growth has been performed by Molecular Beam Epitaxy. The n layer with thickness of 1μm and electron concentration of 6 * 1017 cm-3 has been grown on a p-type GaAs substrate with hole concentration of 1 * 1017cm-3. During growth, in situ monitoring of the layer stoichiometry has been made possible by using Reflection High Energy Electron Diffraction technique. After growth characterization was performed by the use of Hall-effect measurement, the results for the carrier concentration was further confirmed by Electrochemical Capacitance-Voltage profiling technique

  3. 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.

  4. 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.

  5. 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

    International Nuclear Information System (INIS)

    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

  6. 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.

  7. 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. PMID:26758803

  8. 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.

  9. 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.

  10. 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?

  11. 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.

  12. Mapping and measuring place attachment

    DEFF Research Database (Denmark)

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

    2015-01-01

    ) identify how participant socio-demographic and home location attributes influence place attachment, (4) provide some guidance for mapping place attachment in future research. We found large spatial variability in individual place attachment and mapped landscape values using both area and distance......-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...... attachment with just over half of landscape values located outside the area of mapped place attachment. Economic livelihood values, as an indicator of place dependence, and social values, as an indicator of place identity, are more likely to be mapped within the place attachment area. Aggregated place...

  13. 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.

  14. Adult Attachment and Developmental Personality Styles: An Empirical Study

    Science.gov (United States)

    Sherry, Alissa; Lyddon, William J.; Henson, Robin K.

    2007-01-01

    The current study was designed to test specific hypotheses associated with W. J. Lyddon and A. Sherry's (2001) attachment theory model of developmental personality styles. More specifically, 4 adult attachment dimensions were correlated with 10 personality scales on the Millon Clinical Multiaxial Inventory-III (T. Millon, R. Davis, & C. Millon,…

  15. 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.

  16. A comparison of stress distribution and flexion among various designs of bar attachments for implant overdentures: A three dimensional finite element analysis

    Directory of Open Access Journals (Sweden)

    Prakash Vijay

    2009-01-01

    Full Text Available Context: Bar overdentures are popular choices among clinicians worldwide but configurations that provide an optimal biomechanical distribution of stress are still debatable. Aims: To compare the stresses and elastic flexion between implant supported bar overdentures in various configurations using finite element analysis. Settings and Design: A CAT scan of a human mandible was used to generate an anatomically accurate mechanical model. Materials and Methods: Three models with bars and clips in three different configurations were constructed. Model 1 had a single bar connecting two implants, Model 2 had three bars connecting all the four implants, and Model 3 had two bars connecting the medial and distal implants on the sides only. The models were loaded under static conditions with 100N load distributed at the approximate position of the clip. The mandibular boundary conditions were modeled considering the real geometry of its muscle supporting system. Maximum von Mises stress at the level of the bar and at the bone implant interface were compared in all three models. The flexion of mandible and the bar was also compared qualitatively. Statistical Analysis Used: The analyses were accomplished using the ANSYS software program and were processed by a personal computer. Stress on these models was analyzed after loading conditions. Results: Qualitative comparisons showed that stress at the level of the bar and at the bone implant interface were in the following order: Model 1> Model 3> Model 2. The flexion of the mandible and the bar were in the following order: Model 2 > Model 1 > Model 3. Conclusions: Four implant bar systems connected by bars on the sides only is a better choice than two implant bar systems and four implant bar systems with bars connecting all four implants.

  17. Design, synthesis, antimicrobial activity and molecular modeling studies of novel benzofuroxan derivatives against Staphylococcus aureus.

    Science.gov (United States)

    Jorge, Salomão Dória; Masunari, Andrea; Rangel-Yagui, Carlota Oliveira; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa

    2009-04-15

    Molecular modification is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N'-(benzofuroxan-5-yl)methylene]benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect. These properties were also evaluated through the lipophilic and electrostatic potential maps, respectively, considering the compounds with better biological profile. Twelve compounds exhibited similar bacteriostatic activity against standard and multidrug-resistant strains. The most active compound was the 4-CF(3) substituted derivative, which presented a minimum inhibitory concentration (MIC) value of 14.6-13.1 microg/mL, and a ClogP value of 1.87. The results highlight the benzofuroxan derivatives as potential leads for designing new future antimicrobial drug candidates. PMID:19324556

  18. 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.

  19. Rational design of molecularly imprinted polymer: the choice of cross-linker.

    Science.gov (United States)

    Muhammad, Turghun; Nur, Zohre; Piletska, Elena V; Yimit, Osmanjan; Piletsky, Sergey A

    2012-06-01

    The paper describes a rational approach for the selection of cross-linkers during the development of molecularly imprinted polymers (MIPs). As a model system for this research MIPs specific for the drug zidovudine (AZT) were designed and tested. Three cross-linkers trimethylolpropane trimethacrylate (TRIM), ethylene glycol dimethacrylate (EGDMA) and divinylbenzene (DVB) were studied. The analogue of zidovudine (AZT) ester (AZT-ES) was used as a dummy template. The imprinting factors for all of the polymers in the static adsorption experiments were calculated. The data on the AZT adsorption by control polymers (CP), which were prepared with different cross-linkers without a functional monomer, was also analyzed. DVB was found to be more inert towards zidovudine than EGDMA and TRIM, which was confirmed by both molecular modelling and adsorption experiments. It was demonstrated that DVB-based polymers had a higher imprinting factor (I = 1.85) compared with other tested cross-linked polymers. It was suggested that the selection of the cross-linker should be based on the strength of the interaction with the template: the cross-linker which displays lower binding of the template should be preferential because it generates MIPs with lower non-specific binding and a higher imprinting factor, and therefore specificity. Which cross-linker to use for the preparation of any particular MIP can be determined by analysis of the interactions between the cross-linker and template. This could be done either virtually using computational modelling or by template adsorption using a small library of polymers prepared using different cross-linkers. PMID:22534800

  20. 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

  1. 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.

  2. Attachment theory: Old and new approach

    OpenAIRE

    Polovina Nada

    2005-01-01

    The article is an attempt to present holistically the key concepts of attachment theory rediscovered for its potentials. The presented concepts include: narrow definition of attachment, behavioral control system of attachment, attachment working model and patterns of attachment. The concepts are presented in the context of child attachment theory and adult attachment theory, in addition to description of the development of attachment. Concepts, as well as developmental processes are presented...

  3. 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

  4. Attachment theory and therapeutic relationships

    OpenAIRE

    Boysan, Zehra

    2015-01-01

    The aims of this study were to examine the associations between current self-reported attachment styles, retrospective reports of childhood experiences, and the development of the therapeutic alliance. It was hypothesised that anxious and avoidant attachment would be correlated with negative childhood experiences and that both attachment anxiety and avoidance would be inversely correlated with the therapeutic alliance. The third hypothesis stated that negative childhood recollections would co...

  5. 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...

  6. Design and fabrication of a new class of nano hybrid materials based on reactive polymeric molecular cages.

    Science.gov (United States)

    Zhang, De Suo; Liu, Xiang Yang; Li, Jing Liang; Xu, Hong Yao; Lin, Hong; Chen, Yu Yue

    2013-09-10

    This paper describes a strategy of fabricating a new class of nano hybrid particles in terms of the "nanocages" of reactive molecular matrices/networks. The concept is to design molecular matrices functionalized with particular reactive groups, which can on-site synthesize and fix nanoparticles at the designated positions of the molecular networks. The cages of the molecular networks impose the confinement and protection to the nanoparticles so that the size and the stability of nano hybrid particles can be better controlled. To this end, polyamide network polymers (PNP) were synthesized and adopted as the reactive molecular cages for the control of silver nanoparticles formation. It follows that the silver nano hybrid particles fabricated by this method have an average diameter of 4.34 nm much smaller than any other or similar methods ie by a hyperbranched polyamide polymer (HB-PA). As per our design, the size of the silver nano hybrid particles can also be tuned by controlling the molar ratio between silver ions and the functional groups in the polymeric matrices. The silver nano hybrid particles reveal the substantially enhanced stability in aqueous solutions, which gives rise to the long stable performance of localized surface plasmon resonance. As the nano hybrid particles display long eminent nanoeffects, they exert broad implications for a wide range of applications such as biomedicine, catalysis, and optoelectronics. PMID:23980927

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

    2016-07-14

    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. PMID:27376633

  12. 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

  13. 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

  14. 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…

  15. 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…

  16. Exploring the boundaries of a light-driven molecular motor design : new sterically overcrowded alkenes with preferred direction of rotation

    NARCIS (Netherlands)

    van Delden, Richard; ter Wiel, Matthijs; de Jong, Herman; Meetsma, Auke; Feringa, Bernard

    2004-01-01

    Insight in the steric and electronic parameters governing isomerization processes in artificial molecular motors is essential in order to design more advanced motor systems. A subtle balance of steric parameters and the combination of helical and central chirality are key features of light-driven un

  17. 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

  18. Chalcone based azacarboline analogues as novel antitubulin agents: design, synthesis, biological evaluation and molecular modelling studies.

    Science.gov (United States)

    Sharma, Sahil; Kaur, Charanjit; Budhiraja, Abhishek; Nepali, Kunal; Gupta, Manish K; Saxena, A K; Bedi, P M S

    2014-10-01

    The present study involves the design of a series of 3-aryl-9-acetyl-pyridazino[3,4-b]indoles as constrained chalcone analogues. A retrosynthetic route was proposed for the synthesis of target compounds. All the synthesized compounds were evaluated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and A-549 human cancer cell lines. The results indicated that 2a, 3a, 5a and 6a possessed significant cytotoxic potential with an IC50 value ranging from 1.13 to 5.76 μM. Structure activity relationship revealed that the nature of both Ring A and Ring B influences the activity. Substitution of methoxy groups on the phenyl ring (Ring A) and unsubstituted phenyl ring (Ring B) were found to be the preferred structural features. The most potent compound 2a was further tested for tubulin inhibition. Compound 2a was found to significantly inhibit the tubulin polymerization (IC50 value - 2.41 μM against THP-1). Compound 2a also caused disruption of microtubule assembly as evidenced by Immunoflourescence technique. The significant cytotoxicity and tubulin inhibition by 2a was rationalized by molecular modelling studies. The most potent structure was docked at colchicine binding site (PDB ID-1SA0) and was found to be stabilized in the cavity via various hydrophobic and hydrogen bonding interactions. PMID:25128667

  19. 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.

  20. Molecular Design for Tailoring a Single-Source Precursor for Bismuth Ferrite.

    Science.gov (United States)

    Bendt, Georg; Schiwon, Rafael; Salamon, Soma; Landers, Joachim; Hagemann, Ulrich; Limberg, Christian; Wende, Heiko; Schulz, Stephan

    2016-08-01

    Nearly phase-pure bismuth ferrite particles were formed by thermolysis of the single-source precursor [Cp(CO)2FeBi(OAc)2] (1) in octadecene at 245 °C, followed by subsequent calcination at 600 °C for 3 h. In contrast, the slightly modified compound [Cp(CO)2FeBi(O2C(t)Bu)2] (2) yielded only mixtures of different bismuth oxide phases, revealing the distinctive influence of molecular design in material synthesis. The chemical composition, morphology, and crystallinity of the resulting materials were investigated by X-ray diffraction, transmission electron microscopy, and energy-dispersive X-ray spectroscopy. In addition, the optical properties were investigated by Fourier transform infrared and UV-vis spectroscopies, showing a strong band gap absorption in the visible range at 590 nm (2.2 eV). The magnetic behavior was probed by vibrating-sample and superconducting quantum interference device magnetometry, as well as (57)Fe Mössbauer spectroscopy. PMID:27391769

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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. PMID:25815400

  9. Molecular modeling methods in the study and design of bioactive compounds: An introduction [Métodos de Modelagem Molecular para estudo e planejamento de compostos bioativos: Uma introdução

    OpenAIRE

    Carlos Mauricio R. Sant´Anna

    2009-01-01

    This paper presents an introduction to the main methods used in molecular modeling calculations applied in the design of bioactive compounds. An introductory description of the two approaches methods predominantly used in molecular modeling studies is presented: the classical approach, which includes molecular mechanics and molecular dynamics; and the quantum mechanical approach, which includes ab initio and semi-empirical methods. We discuss how these methods can be applied to determine the ...

  10. Examinations on retention of overdentures with elastic frictional attachments

    Directory of Open Access Journals (Sweden)

    W. Chladek

    2010-11-01

    Full Text Available frictional attachments.Design/methodology/approach: The examinations of retention characteristics of traditional attachments, elastic frictional attachments and models of overdentures have been carried out using Zwick testing machine. Retention forces and work essential for separating the attachments have been determined as well. Next the force – displacement characteristics for overdenture model have been registered for two places where the force was applied and for three inclination angles of the line of application of force.Findings: The obtained results of laboratory examinations gave evidence of high effectiveness of elastic frictional attachments.Research limitations/implications: It has not been possible to register mechanical characteristics due to limitations of clinical conditions. Wide analysis of retention characteristics requires examinations carried out in laboratory conditions.Practical implications: Thorough analysis of force - displacement characteristics enables to understand better the mechanisms which are essential for the effectiveness of particular attachments. Applying such knowledge in practice helps to use more effectively the properties of silicone rubbers for making the elastic frictional attachments.Originality/value: The presented method of evaluating the effectiveness of attachments is based on determining retention work of the attachments and it allows to compare quite objectively even relatively different solutions. The so far used criterion of measuring vertical retention force makes it possible to compare only the solutions which are based on similar mechanical principles.

  11. Diameters in preferential attachment models

    NARCIS (Netherlands)

    Dommers, S.; Van der Hofstad, R.; Hooghiemstra, G.

    2010-01-01

    In this paper, we investigate the diameter in preferential attachment (PA-) models, thus quantifying the statement that these models are small worlds. The models studied here are such that edges are attached to older vertices proportional to the degree plus a constant, i.e., we consider affine PA-mo

  12. Association between attachment and schizotypy

    OpenAIRE

    Dunne, Colm

    2011-01-01

    Background: The human genome project has affirmed the importance of non-genetic factors in human development. Attachment style is considered to be a diathesis for psychopathology and an important determinant regarding interpersonal functioning. Epidemiological research has indicated that there is significant aetiological continuity between symptoms of schizotypy and clinical symptoms of schizophrenia. Limited research has investigated the association between attachment and schi...

  13. 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

  14. 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

  15. [Set of radiocirculographic attachments for radioisotope laboratories].

    Science.gov (United States)

    Devishev, M I; Panfilova, N P; Ostrogradskaia, M G

    1980-01-01

    A set of radiocirculographic attachments is offered which serves for calibration and verification of readings taken from the apparatus during radiographic procedures. The set is designed for operation with all colimators of radiocirculographs produced in the USSR and Hungarian People's Republic. The set is able to imitate the investigation geometry, accumulation of radioactivity in the organ under study, absorption and scattering of radioactivty in the organism tissues. Series production of this device has already been initiated. PMID:7392870

  16. Computer-Assisted Drug Design: Genetic Algorithms and Structures of Molecular Clusters of Aromatic Hydrocarbons and Actinomycin D-Deoxyguanosine

    Science.gov (United States)

    Xiao, Yong Liang

    Molecular packing, clustering, and docking computations have been performed by empirical intermolecular energy minimization methods. The main focus of this study is finding a robust global search algorithm to solve intermolecular interaction problems, especially to apply an efficient algorithm to large-scale complex molecular systems such as drug-DNA binding or site selectivity which has increasing importance in drug design and drug discovery. Molecular packing in benzene, naphthalene, and anthracene crystals is analyzed in terms of molecular dimer interaction. Intermolecular energies of the gas dimer molecules are calculated for various intermolecular distances and orientations using empirical potential energy functions. The gas dimers are compared to pairs of molecules extracted from the observed crystal structures. Net atomic charges are obtained by the potential-derived method from 6-31G and 6-31G^{**} level ab initio wavefunctions. A new approach using a genetic algorithm is applied to predict structures of benzene, naphthalene, and anthracene molecular clusters. The computer program GAME (genetic algorithm for minimization of energy) has been developed to obtain the global energy minimum of clusters of dimer, trimer, and tetramer molecules. This test model has been further developed to applications of molecular docking. Docking calculations of deoxyguanosine molecules to actinomycin D were performed successfully to identify the binding sites of the drug molecule, which was revealed by actinomycin D-deoxyguanosine complex from the solved x-ray crystal structure. The comparison between the evolutionary computing method and conventional local optimization methods concluded that genetic algorithms are very competitive when it comes to complex, large-scale optimization. Full power of genetic algorithms can be unveiled in computer-assisted drug design only when the difficulties of including optimized molecular conformation in the algorithm are overcome. These

  17. Remedial Action Plan and Site Design for Stabilization of the Inactive Uranium Mill Tailings Sites at Slick Rock, Colorado: Appendix B to Attachment 3, Lithologic logs and monitor well construction information. Final report

    International Nuclear Information System (INIS)

    This volume contains lithology logs and monitor well construction information for: NC processing site; UC processing site; and Burro Canyon disposal site. This information pertains to the ground water hydrology investigations which is attachment 3 of this series of reports

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

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. 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. PMID:27492087

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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....

  9. Direction-Specific Interactions Control Crystal Growth by Oriented Attachment

    Science.gov (United States)

    Li, Dongsheng; Nielsen, Michael H.; Lee, Jonathan R. I.; Frandsen, Cathrine; Banfield, Jillian F.; De Yoreo, James J.

    2012-05-01

    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. 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…

  11. Molecular modeling methods in the study and design of bioactive compounds: An introduction [Métodos de Modelagem Molecular para estudo e planejamento de compostos bioativos: Uma introdução

    Directory of Open Access Journals (Sweden)

    Carlos Mauricio R. Sant´Anna

    2009-01-01

    Full Text Available This paper presents an introduction to the main methods used in molecular modeling calculations applied in the design of bioactive compounds. An introductory description of the two approaches methods predominantly used in molecular modeling studies is presented: the classical approach, which includes molecular mechanics and molecular dynamics; and the quantum mechanical approach, which includes ab initio and semi-empirical methods. We discuss how these methods can be applied to determine the molecular structure and properties from these compounds and how to make the best choice according to the problem being addressed.

  12. Shuttle-Attached Manipulator System requirements.

    Science.gov (United States)

    Bodey, C. E.; Cepollina, F. J.

    1973-01-01

    Shuttle mission requirements and cost objectives have led to the selection of a Shuttle-Attached Manipulator System (SAMS) as a general purpose mechanism for docking, payload handling, and the general launch and retrieval of free-flying satellites. SAMS design requirements are discussed, giving attention to end effectors, kinematics, timelines, dynamics, load ratings, TV cameras and lights. Requirements for low-cost payload satellites are considered, taking into account satellites with modular subsystems which are designed for replacement and for resupply in orbit by SAMS.

  13. 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.

  14. 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.

  15. Design principles of molecular networks revealed by global comparisons and composite motifs

    OpenAIRE

    Yu, Haiyuan; Xia, Yu; Trifonov, Valery; Gerstein, Mark

    2006-01-01

    Background Molecular networks are of current interest, particularly with the publication of many large-scale datasets. Previous analyses have focused on topologic structures of individual networks. Results Here, we present a global comparison of four basic molecular networks: regulatory, co-expression, interaction, and metabolic. In terms of overall topologic correlation - whether nearby proteins in one network are close in another - we find that the four are quite similar. However, focusing ...

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

    OpenAIRE

    Bowsher, James; Yan, Susu; Roper, Justin; Giles, William; Yin, Fang-Fang

    2013-01-01

    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 S...

  17. Simulation of Molecular Signaling in Blood Vessels: Software Design and Application to Atherogenesis

    OpenAIRE

    Felicetti, Luca; Femminella, Mauro; Reali, Gianluca

    2013-01-01

    This paper presents a software platform, named BiNS2, able to simulate diffusion-based molecular communications with drift inside blood vessels. The contribution of the paper is twofold. First a detailed description of the simulator is given, under the software engineering point of view, by highlighting the innovations and optimizations introduced. Their introduction into the previous version of the BiNS simulator was needed to provide to functions for simulating molecular signaling and commu...

  18. 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. PMID:21838647

  19. Social attachments and traumatic stress

    Directory of Open Access Journals (Sweden)

    Richard A. Bryant

    2016-03-01

    Full Text Available The extent to which we engage with our social world has been central to our survival as a species and, accordingly, is relevant to how we cope with trauma and adversity. This review summarises current knowledge about the importance of social connections from an evolutionary perspective, as well as integrating this with a discussion of prevailing attachment theories. Experimental research supporting the potential benefit of attachments for managing adversity are presented, along with a review of how these benefits are moderated by individual differences in attachment style. The potential impact of trauma on attachment systems, and the manner in which this can compound trauma stress is discussed. Finally, a broader overview of social network analysis is introduced and it is proposed that a more sociocentric framework of trauma response would promote a fuller understanding of how social processes moderate trauma response.

  20. Porphyrin architectures tailored for studies of molecular information storage.

    Science.gov (United States)

    Carcel, Carole M; Laha, Joydev K; Loewe, Robert S; Thamyongkit, Patchanita; Schweikart, Karl-Heinz; Misra, Veena; Bocian, David F; Lindsey, Jonathan S

    2004-10-01

    A molecular approach to information storage employs redox-active molecules tethered to an electroactive surface. Zinc porphyrins tethered to Au(111) or Si(100) provide a benchmark for studies of information storage. Three sets of porphyrins have been synthesized for studies of the interplay of molecular design and charge-storage properties: (1) A set of porphyrins is described for probing the effect of surface attachment atom on electron-transfer kinetics. Each porphyrin bears a meso-CH2X group for surface attachment where X = OH, SAc, or SeAc. (2) A set of porphyrins is described for studying the effect of surface-charge density in monolayers. Each porphyrin bears a benzyl alcohol for surface attachment and three nonlinking meso substituents of a controlled degree of bulkiness. (3) A set of porphyrins is described that enables investigation of on-chip patterning of the electrolyte. Each porphyrin bears a formyl group distal to the surface attachment group for subsequent derivatization with a molecular entity that comprises the electrolyte. Taken together, this collection of molecules enables a variety of studies to elucidate design issues in molecular-based information storage. PMID:15387598

  1. Electron attachment to fluorocarbon radicals

    Science.gov (United States)

    Shuman, Nicholas

    2014-10-01

    Most plasma environments contain populations of short-lived species such as radicals, the chemistry of which can have significant effects on the overall chemistry of the system. However, few experimental measurements of the kinetics of electron attachment to radicals exist due to the inherent difficulties of working with transient species. Calculations from first principles have been attempted, but are arduous and, because electron attachment is so sensitive to the specifics of the potential surface, their accuracy has not been established. Electron attachment to small fluorocarbon radicals is particularly important, as the data are needed for predictive modeling of plasma etching of semiconductor materials, a key process in the industrial fabrication of microelectronics. We have recently developed a novel flowing afterglow technique to measure several types of otherwise difficult to study plasma processes, including thermal electron attachment to radicals. Variable Electron and Neutral Density Attachment Mass Spectrometry (VENDAMS) exploits dissociative electron attachment in a weakly ionized plasma as a radical source. Here, we apply VENDAMS to a series of halofluorocarbon precursors in order to measure the kinetics of thermal electron attachment to fluorocarbon radicals. Results are presented for CF2, CF3, C2F5,C2F3,1-C3F7, 2-C3F7, and C3F5 from 300 K to 900 K. Both the magnitude and the temperature dependences of rate coefficients as well as product branching between associative and dissociative attachment are highly system specific; however, thermal attachment to all species is inefficient, never exceeding 5% of the collision rate. The data are analyzed using a recently developed kinetic modeling approach, which uses extended Vogt-Wannier theory as a starting point, accounts for dynamic effects such as coupling between the electron and nuclear motions through empirically validated functional forms, and finally uses statistical theory to determine the fate of

  2. 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.

  3. 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....

  4. The evaluation of selected attachment systems for implant-retained overdenture based on retention characteristics analysis.

    Science.gov (United States)

    Chladek, Grzegorz; Wrzuś-Wieliński, Marcin

    2010-01-01

    The results of mechanical characteristics of attachments used for retaining and stabilizing overdenture have been analysed. Two commercially used attachments (a ball attachment and a bar attachment) and elastic frictional attachments designed by the research team with Professor Chladek as the leader have been investigated. The diagrams of force-displacement characteristics have been registered. Retention forces (F(R)) have been determined and total work (W(T)) disconnecting the attachments has been calculated on the basis of these diagrams. The analysis of total work corresponding to different types of attachments made it possible to distinguish some characteristic areas which illustrate specific features of particular designs. It has been revealed that determining the retention force allows us to compare only the attachments which work on similar bases. In order to conduct a purely objective comparison of the efficiency of different designs, it is necessary to analyze complete force-displacement characteristics as well as to determine on this basis the subsequent phases of separating the parts of attachments and to find the value of the work which in fact determines their quality. The comparison of selected commercially used designs and the presented elastic frictional attachments (taking into account the criterion of work) gives clear evidence that the introduced design of attachment enables us to create very good conditions of retaining overdenture. PMID:21247057

  5. 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

    2016-01-01

    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. PMID:26999083

  6. 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.

  7. 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. PMID:25982493

  8. 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.

  9. 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

  10. 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.

  11. Computer-aided de novo ligand design and docking/molecular dynamics study of vitamin D receptor agonists.

    Science.gov (United States)

    Shen, Xiu-Long; Takimoto-Kamimura, Midori; Wei, Jing; Gao, Qing-Zhi

    2012-01-01

    1α,25(OH)(2)D(3), which is directly mediated by the vitamin D receptor (VDR), exerts a wide variety of biological actions. However, the treatment with 1α,25(OH)(2)D(3) is limited because of its side effects. Many analogs and several nonsteroidal mimics with potent biological activity have been reported so far, and our rationale for designing the VDR agonists was on the basis of computer-aided drug design method by de novo design of A-ring and C/D-ring position of 1α,25(OH)(2)D(3). Pyrimidine-2,4-diamine was selected as A-ring, and naphthalene and benzene were chosen as C/D-ring. By linking different components, a virtue compound library was obtained. To evaluate the contribution to activity of each component, we performed a series of automated molecular docking operations. Results revealed that the 19-dimethyl derivatives (the C-19 position correspond to C-20 in 1α,25(OH)(2)D(3)) show the favorable docking affinity to VDR. Moreover, the docking results are quite robust when further validated by molecular dynamics simulations. In addition, by free energy analysis using molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method, the driving force of the binding between VDR and the ligands is proved to be hydrophobic interactions. Thus, a possible strategy to design new series of VDR agonists is proposed. The strategy can be successfully applied to explain the high potential activities of the 19-dimethyl derivatives. It is anticipated that the findings reported here may provide useful information for designing effective VDR agonists as well as the therapeutic treatment of VDR-related diseases. PMID:21523537

  12. Attachment and the Body in Suicidal Adolescents: A Pilot Study

    OpenAIRE

    Wright, John; Briggs, Stephen; Behringer, Johanna

    2013-01-01

    There is a relative dearth of studies in the field of adolescent attachment despite the potential impact of such developmental changes on the organization of attachment systems. This omission is even more acute among clinical populations, although adolescence is notable for dramatic increases in specific psychopathologies, e.g. eating disorders, delinquency, and suicide and self-harm. This article attempts to address the shortfall using a mixed quantitative/qualitative research design. First,...

  13. 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

  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. Design of a novel molecular beacon: modification of the stem with artificially genetic alphabet†

    OpenAIRE

    Sheng, Pinpin; Yang, Zunyi; Kim, Youngmi; Wu, Yanrong; Tan, Weihong; Benner, Steven A

    2008-01-01

    A molecular beacon that incorporates components of an artificially expanded genetic information system (Aegis) in its stem is shown not to be opened by unwanted stem invasion by adventitious standard DNA; this should improve the “darkness” of the beacon in real-world applications.

  17. 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…

  18. 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...

  19. Activating Attachments Reduces Memories of Traumatic Images.

    Science.gov (United States)

    Bryant, Richard A; Foord, Rachael

    2016-01-01

    Emotional memories, and especially intrusive memories, are a common feature of many psychological disorders, and are overconsolidated by stress. Attachment theory posits that activation of mental representations of attachment figures can reduce stress and boost coping. This study tested the proposition that attachment activation would reduce consolidation of emotional and intrusive memories. Sixty-seven undergraduate students viewed subliminal presentations of traumatic and neutral images, which were preceded by subliminal presentations of either attachment-related images or non-attachment-related images; free recall and intrusive memories were assessed two days later. Participants with low avoidant attachment tendencies who received the attachment primes recalled fewer memories and reported fewer intrusions than those who received the non-attachment primes. Unexpectedly, those with high anxious attachment tendencies reported fewer memories. These findings generally accord with attachment theory, and suggest that consolidation of emotional memories can be moderated by activation of attachment representations. PMID:27631498

  20. Design rules for rational control of polymer glass formation behavior and mechanical properties with small molecular additives

    Science.gov (United States)

    Mangalara, Jayachandra Hari; Simmons, David

    Small molecule additives have long been employed to tune polymers' glass formation, mechanical and transport properties. For example, plasticizers are commonly employed to suppress polymer Tg and soften the glassy state, while antiplasticizers, which stiffen the glassy state of a polymer while suppressing its Tg, are employed to enhance protein and tissue preservation in sugar glasses. Recent literature indicates that additives can have a wide range of possible effects, but all of these have not been clearly understood and well appreciated. Here we employ molecular dynamics simulations to establish design rules for the selection of small molecule additives with size, molecular stiffness, and interaction energy chosen to achieve targeted effects on polymer properties. We furthermore find that a given additive's effect on a polymer's Tg can be predicted from its Debye-Waller factor via a function previously found to describe nanoconfinement effects on the glass transition. These results emphasize the potential for a new generation of targeted molecular additives to contribute to more targeted rational design of polymers. We acknowledge the Keck Foundation and the Ohio Supercomputing Center for financial and computational support of this effort, respectively.

  1. Palmitate Luciferin: A molecular design for the second harmonic generation study of ion complexation at the air-water interface

    International Nuclear Information System (INIS)

    A molecular organic chromophore, Palmitate-Luciferin, has been synthesized for studying ion complexation at the air-water interface using second harmonic generation (SHG). This molecule was designed through the addition of a long hydrophobic palmitoyl alkyl chain to the aromatic π-electron system of Luciferin. We first demonstrate that this organic chromophore is a potential candidate for SHG studies of ion complexation with the measurement of its first hyper-polarizability in aqueous solutions by hyper Rayleigh scattering (HRS) with and without calcium ions. Then, we characterize the Palmitate-Luciferin surfactant properties at the air-water interface combining surface tension measurements with a surface SHG study and Brewster angle imaging. These results allow us to build a molecular description of the chromophore at the interface and observe its molecular reorganization during the monolayer compression leading to the formation of aggregates. Finally, we show that the initial goal of the designing work is achieved since Palmitate-Luciferin indeed exhibits a higher SHG response in the presence of calcium ions in the aqueous sub-phase as expected. (authors)

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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...

  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. Diameters in preferential attachment models

    OpenAIRE

    Dommers, S.; van der Hofstad, R.; Hooghiemstra, G.

    2010-01-01

    In this paper, we investigate the diameter in preferential attachment (PA-) models, thus quantifying the statement that these models are small worlds. The models studied here are such that edges are attached to older vertices proportional to the degree plus a constant, i.e., we consider affine PA-models. There is a substantial amount of literature proving that, quite generally, PA-graphs possess power-law degree sequences with a power-law exponent \\tau>2. We prove that the diameter of the PA-...

  10. 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).

  11. 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.

  12. 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.

  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 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.

  15. Selective self-assembly of molecular clusters with designed sizes on metal surfaces

    Science.gov (United States)

    Wang, Jun; Li, Qing; Fuentes-Cabrera, Miguel; Sumpter, Bobby G.; Baddorf, Arthur P.; Pan, Minghu

    2014-03-01

    The self-assembly of ``magic'' molecular clusters on various substrates provides a new arena for studies of surface nanocatalysis and molecular electronics. Here we present the self-assembly of phenylacetylene molecules on Cu(100) by a combined low-temperature STM and in-depth density functional theory investigation. We observe the molecules form distinct tetramer clusters on Cu(100) at 40 K. Each cluster has a four-fold symmetry and consists of four molecules. A delicate balance of intramolecular and dipole-dipole interactions between clusters maintains this magic tetramer configuration on Cu(100). The strong interaction between the molecules and the copper surface creates an anchor at each adsorption site. Through comparison with our previous observed hexamer (six-molecule) clusters on Au(111), we conclude that the epitaxial relationship between the molecules and metal surfaces is crucial in defining magic numbers of surface-supported molecular clusters under weak intermolecular interaction. This research was conducted at the Center for Nanophase Materials Sciences, which is sponsored at Oak Ridge National Laboratory by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy.

  16. 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. PMID:26017698

  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. 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

  19. 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.

  20. 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...

  1. 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.

  2. Attachment patterns and separation anxiety symptom

    OpenAIRE

    Sakineh - Mofrad; Rohani - Abdullah; Ikechkwu - Uba

    2010-01-01

    Literature suggests that child attachment and anxiety symptoms are related. One purpose of the present study was to assess whether attachment patterns related differently to separation anxiety symptoms (fear of being alone, and fear of abandonment). Three attachment patterns assessed were secure, avoidant and ambivalent attachment. Findings indicated that ambivalent attachment was most consistently related with higher separation anxiety symptom. And also, different associations were found bet...

  3. PRECISION ATTACHMENTS; APPLICATIONS AND LIMITATIONS

    Directory of Open Access Journals (Sweden)

    Prabhakar

    2012-12-01

    Full Text Available ABSTRACT: A unique concern of a removable denture when compare d to others is retention. Retention is the ability of the prosthesis to resist the movement of denture away from the supporting tissues/teeth. The component of removable d enture which provides retention is called as direct retainer. 1,3,4 A direct retainer can be either an extracoronal or intracoronal retainer. Extracoronal direct retainer uses mechanical resistance to displa cement through components placed on external surface of abutment teeth. Intracoronal retainer is either cast or attached to tally within the restored natural contours of an abutment tooth. 1 One of the main drawbacks of extracoronal retainers used in partial dentures is visibility. Many patients find themselves in an aest hetically compromised state when these retainers are placed on teeth in visible area. Preci sion attachments provide solution for this problem. Also, precision attachments provide better ve rtical support and better stimulation to the underlying tissue through intermittent vertical massage. 1,9 Although the history of intracoronal retainers goes back to 5 th and 4 th centuries BC, technically more sound developments began in early 2 0 th century AD, with Dr. Herman E. S. Chayes formulating the principle of internal attachme nt in 1906. Since then precision attachments are playing an important role in removabl e and fixed partial denture, conventional and implant supported overdenture. 9

  4. 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

  5. CD Attached with Books Management System Management System Based on Struts2 File upload Module Design%基于Struts2的随书光盘管理系统文件上传模块设计

    Institute of Scientific and Technical Information of China (English)

    夏宇红; 夏文忠

    2013-01-01

    为有效解决随书光盘文件的上传,以Struts2框架的Common-FileUpload组件为基础,讨论了使用Struts2框架上传文件的开发配置,在满足随书光盘系统功能的情况下,优化系统功能,保证系统性能稳定,方便管理员和读者的使用.%To effectively solve the file upload of CD attached with books, on the basis of the Struts2 framework, Common-FileUpload components, discussed the development configuration using the Struts2 framework, upload files, in the case of system functions meet the CD attached with books, the optimization of system function, system performance is stable, convenient the use of the librarians and readers.

  6. Abnormality Detection in Correlated Gaussian Molecular Nano-Networks: Design and Analysis

    OpenAIRE

    Ghavami, Siavash; Lahouti, Farshad

    2016-01-01

    A nano abnormality detection scheme (NADS) in molecular nano-networks is studied. This is motivated by the fact that early detection of diseases such as cancer play a crucial role in their successful treatment. The proposed NADS is in fact a two-tier network of sensor nano-machines (SNMs) in the first tier and a data-gathering node (DGN) at the sink. The SNMs detect the presence of competitor cells (abnormality) by variations in input and/or parameters of a nano-communications channel (NCC). ...

  7. Design of Far-Red Sensitizing Squaraine Dyes Aiming Towards the Fine Tuning of Dye Molecular Structure.

    Science.gov (United States)

    Morimoto, Takuya; Fujikawa, Naotaka; Ogomi, Yuhei; Pandey, Shyam S; Ma, Tingli; Hayase, Shuzi

    2016-04-01

    Model squaraine dyes having sharp and narrow absorptions mainly in the far-red wavelength region has been logically designed, synthesized and used for their application as sensitizer in the dyesensitized solar cells (DSSC). In order to have fine control on energetics, dyes having same mother core and alkyl chain length varying only in molecular symmetry and position of substituent were designed. It has been found that even keeping all other structural factor constant, only positional variation of substituent leads to not only in the variation of energetics by 0.1 eV but affects the photovoltaic characteristics also. Optimum concentration of dye de-aggregating agent was found to be 100 times with respect to the sensitizing dye concentration. Amongst dyes utilized in this work best performance was obtained for unsymmetrical dye SQ-40 giving a photoconversion efficiency of 4.01% under simulated solar irradiation at global AM 1.5. PMID:27451618

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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. PMID:27248370

  13. 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

  14. 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. PMID:25196371

  15. A modular design of molecular qubits to implement universal quantum gates

    Science.gov (United States)

    Ferrando-Soria, Jesús; Moreno Pineda, Eufemio; Chiesa, Alessandro; Fernandez, Antonio; Magee, Samantha A.; Carretta, Stefano; Santini, Paolo; Vitorica-Yrezabal, Iñigo J.; Tuna, Floriana; Timco, Grigore A.; McInnes, Eric J. L.; Winpenny, Richard E. P.

    2016-04-01

    The physical implementation of quantum information processing relies on individual modules--qubits--and operations that modify such modules either individually or in groups--quantum gates. Two examples of gates that entangle pairs of qubits are the controlled NOT-gate (CNOT) gate, which flips the state of one qubit depending on the state of another, and the gate that brings a two-qubit product state into a superposition involving partially swapping the qubit states. Here we show that through supramolecular chemistry a single simple module, molecular {Cr7Ni} rings, which act as the qubits, can be assembled into structures suitable for either the CNOT or gate by choice of linker, and we characterize these structures by electron spin resonance spectroscopy. We introduce two schemes for implementing such gates with these supramolecular assemblies and perform detailed simulations, based on the measured parameters including decoherence, to demonstrate how the gates would operate.

  16. A modular design of molecular qubits to implement universal quantum gates.

    Science.gov (United States)

    Ferrando-Soria, Jesús; Moreno Pineda, Eufemio; Chiesa, Alessandro; Fernandez, Antonio; Magee, Samantha A; Carretta, Stefano; Santini, Paolo; Vitorica-Yrezabal, Iñigo J; Tuna, Floriana; Timco, Grigore A; McInnes, Eric J L; Winpenny, Richard E P

    2016-01-01

    The physical implementation of quantum information processing relies on individual modules-qubits-and operations that modify such modules either individually or in groups-quantum gates. Two examples of gates that entangle pairs of qubits are the controlled NOT-gate (CNOT) gate, which flips the state of one qubit depending on the state of another, and the gate that brings a two-qubit product state into a superposition involving partially swapping the qubit states. Here we show that through supramolecular chemistry a single simple module, molecular {Cr7Ni} rings, which act as the qubits, can be assembled into structures suitable for either the CNOT or gate by choice of linker, and we characterize these structures by electron spin resonance spectroscopy. We introduce two schemes for implementing such gates with these supramolecular assemblies and perform detailed simulations, based on the measured parameters including decoherence, to demonstrate how the gates would operate. PMID:27109358

  17. 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.

  18. MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

    Science.gov (United States)

    Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

    2016-09-30

    Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27112322

  19. 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.

  20. [First clinical experiences with ceramic ball attachments for overdentures].

    Science.gov (United States)

    Büttel, Adrian E; Schmidli, Fredy; Marinello, Carlo P; Lüthy, Heinz

    2008-01-01

    In this prospective clinical study on 40 patients with similar clinical conditions (edentulous jaw with 2 interforaminal implants) commercially available ceramic ball attachments (ruby) were compared to commercial titanium ball attachments. The primary aim of the study was to measure the wear of the ball attachments after being 1 year in function. However, in the course of the study already after 7 to 12 months multiple failures with ceramic ball attachments occurred. Twelve (28%) of 43 ceramic ball attachments had to be replaced, mostly because of fractures (8) of the ceramic ball. It seems that ceramic ball attachments of the investigated design are not able to withstand normal intraoral stresses. The short-term susceptibility to fractures didn't allow to examine the ceramic-inherent features such as compressive strength and wear resistance. Furthermore, a secure connection between a titan base and a ceramic ball seems to be challenging. Based on these results, in implant-retained removable prosthesis the use of metal-based retainers is still recommended, although during maintenance a higher wear has to be expected. This wear can be compensated by either activating or changing the matrix or the patrix. PMID:18293602

  1. 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.

  2. 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. PMID:23960557

  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. 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.

  5. Attachment and continuing bonds in bereavement

    Directory of Open Access Journals (Sweden)

    Anja Simonič

    2006-03-01

    Full Text Available The subject of this paper is the attachment in a relationship being one of the factors which co-form the grieving process after conjugal loss. In this integrative study about the grieving process after the loss of a partner due to sudden or expected death one or two years after the loss, the author determined that the relationship between partners represents an important indicator of the grieving process. Due to the sensitive nature of the process, the method used was a case study (seven participants were interviewed and a circular research process. The functioning of grieving persons in different areas of life was assessed with a semi-structured interview, specifically designed for this research, and with an adapted version of the Attachment Test, a part of Picture Test of Separation and Individuation (Žvelc and Žvelc, 2000. It was ascertained that particular contents in the grieving process are specifically connected with the type of relationship prior to death (ambivalent and closely connected/dependent relationship and the experiencing of the present position in relation to the deceased partner. Due to the fact that knowledge about possible maintenance/continuance of the bond between the partners has only recently become the locus of empirical research, the present study could not yet fully evaluate what kind of experience of current relationship position towards the partner contributes to healthy separation and individuation processes, i.e. grieving. Although the findings are limited to the specific context of each individual participant, the case study ascertained certain patterns in the relation between the grieving process and the attachment between partners, which indicates that there is a possibility of these in the wider population.

  6. 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.

  7. Design of novel porous melamine-formaldehyde materials for molecular recognition

    OpenAIRE

    Meghani, Lina

    2011-01-01

    Porous materials have played a pivotal role in the hosting of guest species. They provide a good diffusion medium, display high surface area and often the pores are size specific and bear the correct functionality to enhance retention of analytes. This work shows how such materials, based on melamine-formaldehyde (MF) chemistry are designed. The melamine motif has been known to form supramolecular aggregates in solution with other triazine-containing molecules. It was, thus, anticipated t...

  8. Molecular design of Calix[4]arene derivatives for uranyl ion extraction from aqueous media

    International Nuclear Information System (INIS)

    Uranyl ion extraction is an important part of nuclear waste reprocessing. Use of organic ligands having chelating property with uranyl ions is a promising tool in this area, because of the possibility to improve the selectivity and the affinity of the ligands towards uranyl ions. In this study, Calix[4]arene derivatives containing B, Al, C, Si, N, P, O and S elements in bridging positions were designed and their chelating energetics with uranyl cation are calculated by means of DFT methods.

  9. Nonlinear relaxation dynamics in elastic networks and design principles of molecular machines

    OpenAIRE

    Togashi, Y.; A. Mikhailov

    2007-01-01

    Analyzing nonlinear conformational relaxation dynamics in elastic networks corresponding to two classical motor proteins, we find that they respond by well defined internal mechanical motions to various initial deformations and that these motions are robust against external perturbations. We show that this behavior is not characteristic for random elastic networks. However, special network architectures with such properties can be designed by evolutionary optimization methods. Using them, an ...

  10. 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.

  11. Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors.

    Directory of Open Access Journals (Sweden)

    Teresa Mairal

    Full Text Available The thyroid hormone and retinol transporter protein known as transthyretin (TTR is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis.

  12. Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors.

    Science.gov (United States)

    Mairal, Teresa; Nieto, Joan; Pinto, Marta; Almeida, Maria Rosário; Gales, Luis; Ballesteros, Alfredo; Barluenga, José; Pérez, Juan J; Vázquez, Jesús T; Centeno, Nuria B; Saraiva, Maria Joao; Damas, Ana M; Planas, Antoni; Arsequell, Gemma; Valencia, Gregorio

    2009-01-01

    The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis. PMID:19125186

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. Design of Multiplex Polymerase Chain Reaction (PCR Method for Molecular Detection of Yersinia pestis Bacterium

    Directory of Open Access Journals (Sweden)

    Mohammad Soleimani

    2010-01-01

    Full Text Available Objective: Yersinia pestis, the causative agent of the zoonotic plague infection, is a majorpublic health concern both as a threat and potential bioweapon. The objective of thepresent study was to establish a uniplex and multiplex - polymerase chain reaction (PCRtest for the specific detection of Y. pestis.Materials and Methods: PCR reactions performed by three pair primers which targetedthe caf1 and pla genes located on the pFra and pPst plasmids and the irp2 chromosomalgene located on the ‘pathogenicity island’. After TA cloning of the PCR products, the test’slimit of detection (LOD was determined. For evaluating the specificity, PCR reactionswere performed with negative control bacteria.Results: Assays were performed with the genome of Y. pestis which produced three DNAfragments of the expected sizes 300, 400 and 520 bp which corresponded to the irp2,caf1 and pla genes, respectively. The lower LoD was 370 copy numbers for the caf1 geneand 21 for the pla gene. In PCR reactions that used negative control bacteria, detectablefragments were not observed.Conclusion: Our method clearly discriminated Y. pestis DNA. The rapidity, specificityand sensitivity of this procedure suggest that it can serve as a useful alternative methodfor the inoculation of laboratory animals or the use of specific culture media for routineplaque surveillance and outbreak investigations. Another vital result of this study was theestablishment of Y. pestis molecular detection technique in Iran.

  19. 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.

  20. Simulational nanoengineering: Molecular dynamics implementation of an atomistic Stirling engine.

    Science.gov (United States)

    Rapaport, D C

    2009-04-01

    A nanoscale-sized Stirling engine with an atomistic working fluid has been modeled using molecular dynamics simulation. The design includes heat exchangers based on thermostats, pistons attached to a flywheel under load, and a regenerator. Key aspects of the behavior, including the time-dependent flows, are described. The model is shown to be capable of stable operation while producing net work at a moderate level of efficiency. PMID:19518394

  1. Simulational nanoengineering: Molecular dynamics implementation of an atomistic Stirling engine

    CERN Document Server

    Rapaport, D C

    2009-01-01

    A nanoscale-sized Stirling engine with an atomistic working fluid has been modeled using molecular dynamics simulation. The design includes heat exchangers based on thermostats, pistons attached to a flywheel under load, and a regenerator. Key aspects of the behavior, including the time-dependent flows, are described. The model is shown to be capable of stable operation while producing net work at a moderate level of efficiency.

  2. Quantum transport and geometric integration for molecular systems

    OpenAIRE

    Odell, Anders

    2010-01-01

    Molecular electronics is envisioned as a possible next step in device miniaturization. It is usually taken to mean the design and manufacturing of electronic devices and applications where organic molecules work as the fundamental functioning unit. It involves the measurement and manipulation of electronic response and transport in molecules attached to conducting leads. Organic molecules have the advantages over conventional solid state electronics of inherent small sizes, endless chemical d...

  3. 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.

  4. A conserved haem redox and trafficking pathway for cofactor attachment

    OpenAIRE

    Richard-Fogal, Cynthia L; Frawley, Elaine R.; Bonner, Eric R.; Zhu, Huifen; San Francisco, Brian; Kranz, Robert G.

    2009-01-01

    A pathway for cytochrome c maturation (Ccm) in bacteria, archaea and eukaryotes (mitochondria) requires the genes encoding eight membrane proteins (CcmABCDEFGH). The CcmABCDE proteins are proposed to traffic haem to the cytochrome c synthetase (CcmF/H) for covalent attachment to cytochrome c by unknown mechanisms. For the first time, we purify pathway complexes with trapped haem to elucidate the molecular mechanisms of haem binding, trafficking and redox control. We discovered an early step i...

  5. 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.

  6. Congruence between molecular phylogeny and cuticular design in Echiniscoidea (Tardigrada, Heterotardigrada)

    DEFF Research Database (Denmark)

    Guil, Noemi; Jorgensen, Aslak; Giribet, Gonzalo;

    2013-01-01

    ornamentation as a phylogenetic character within Echiniscus. To do this, DNA was extracted from single individuals for multiple Echiniscus species, and 18S and 28S rRNA gene fragments were sequenced. Each specimen was photographed, and published in an open database prior to DNA extraction, to make morphological...... genus Diploechiniscus inferred as its sister group, and Testechiniscus as the sister group of this assemblage. Three groups that closely correspond to specific types of cuticular design in Echiniscus have been found with a parsimony network constructed with 18S rRNA data.(c) 2013 The Linnean Society...

  7. 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.

  8. [Strategy of molecular design of drugs: the unification of macro-properties and micro-structures of a molecule].

    Science.gov (United States)

    Guo, Zong-Ru

    2008-03-01

    The interaction of a drug with the organism involves both the disposition of a drug by the organism and the action of a drug on the organism. The disposition of various exogenous substances, including drugs, complies with general rules. The underlying physical and chemical changes to different drugs in view of time and space, i. e. pharmacokinetics, share common characteristics, that is the tout ensemble of a molecule and its macroscopic properties convey direct effect on the pharmacokinetic behavior as the tendency and consequence of biological evolution. The action of a drug on the organism, on the other hand, implicates the physico-chemical binding of a drug molecule to the target protein, which induces pharmacological and toxicological effects. The biological reactions, no matter beneficial or adverse, are all specific and individual manifestation of the drug molecule and determined by the interactive binding between definitive atoms or groups of the drug molecule and the macromolecular target in three-dimension. Such critical atoms, groups, or fragments responsible for the interaction reflect the microscopic structures of drug molecules and are called pharmacophore. In this context, a drug molecule is presumed as an assembly of macroscopic property and microscopic structure, with the macroscopic properties determining the absorption, distribution, metabolism and elimination of drugs and the microscopic structure coining pharmacological action. The knowledge of the internal relationship between macroscopy/microscopy and PK/PD conduces to comprehension of drug action and guides molecular drug design, because this conception facilitates the identification of structural features necessary for biological response, and the determination of factors modulating the physico-chemical and pharmacokinetic properties. The factors determining macro-properties include molecular weight, solubility, charge, lipophilicity (partition), and polar surface area, etc., which are

  9. 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

  10. 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.

  11. 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.

  12. Molecular Design and Immunogenicity of a Multiple-epitope FMDV Antigen and DNA Vaccination

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This article reports the design and construction of a multiple-epitope foot and mouth disease virus (FMDV)antigen, designated as OAAT. This recombinant antigen consists of the structural protein VP1 genes from serotypes A and O FMDV, five major VP1 immunodominant epitopes from two genotypes of Asia1 serotype, and three Th2 epitopes originating from the nonstructural protein, three ABC gene and structural protein VP4 gene. Expressions of target gene from these plasmids in HeLa cells were verified by Western-blot. BALB/c mice were immunized intramuscularly with the DNA vaccines thrice every two weeks. We found that pA could induce simultaneously specific antibodies against serotypes A, Asia1, and O FMDV. Compared to those of the controls, the spots of FMDV-specific IFN-γ and cytotoxic activity from mice immunized with pA were significantly increased. pA provided full protection in 2/4 guinea pigs from challenge with FMDV O/NY00 and Asia1/YNBS/58, respectively. The results show that although pA did not give full protection in 100% immunized guinea pigs from challenge with type O and Asia1 FMDV, respectively, OAAT may be potential immunogen against FMDV and pA may be potential DNA vaccines against FMDV.

  13. Oxytocin enhances the experience of attachment security

    OpenAIRE

    Buchheim, Anna; Heinrichs, Markus; George, Carol; Pokorny, Dan; Koops, Eva; Henningsen, Peter; O’Connor, Mary-Frances; Gundel, Harald

    2009-01-01

    Repeated interactions between infant and caregiver result in either secure or insecure relationship attachment patterns, and insecure attachment may affect individual emotion-regulation and health. Given that oxytocin enhances social approach behavior in animals and humans, we hypothesized that oxytocin might also promote the experience of attachment security in humans. Within a 3-week interval 26 healthy male students classified with an insecure attachment pattern were invited twice to an ex...

  14. Attachment Theory, Foster Parents and Diversity Tolerance

    OpenAIRE

    Kenny, Michael; Fleming, Ted

    2009-01-01

    relevance to attachment within the biological and foster family. Yet every foster parent has a childhood attachment history that influences their interpersonal relationships in adulthood. The primary concern of the foster parent and their supports is with the foster child. But as a result the foster parent may distract or block reflection on their own attachment history. This presentation will focus on attachment theory and the adult, with particular reference to the foster parent. The pre...

  15. Development of foster mother-child attachment

    OpenAIRE

    Korhonen, J

    2014-01-01

    The impact of early attachment relationships and child-adult attachment relationships to children’s social and emotional development has been recognised for a long time. Since the pioneering attachment theories of John Bowlby and Mary Ainsworth highlighting the importance of secure child-adult attachments, many other theories from various perspectives have risen to fill in the gaps. These theories are examined with the framework of foster care in mind. In Finland, the primary solution fo...

  16. 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.

  17. 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.

  18. 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

    2016-01-01

    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. PMID:26761578

  19. Influence of the molecular design on the antifouling performance of poly(ethylene glycol) monolayers grafted on (111) Si.

    Science.gov (United States)

    Perez, Emmanuel; Lahlil, Khalid; Rougeau, Cyrille; Moraillon, Anne; Chazalviel, Jean-Noël; Ozanam, François; Gouget-Laemmel, Anne Chantal

    2012-10-16

    Various poly(ethylene glycol) monomethyl ether moieties were grafted onto hydrogenated silicon surfaces in order to investigate the influence of the molecular design on the antifouling performance of such coatings. The grafted chains were either oligo(ethylene oxide) chains (EG)(n)OMe bound to silicon via Si-O-C covalent bonds, or hybrid alkyl/oligo(ethylene oxide) chains C(p)(EG)(n)OMe bound via Si-C covalent bonds (from home-synthesized precursors). Quantitative IR spectroscopy gave the molecular coverage of the grafted layers, and AFM imaging demonstrated that a proper surfactinated rinse yields C(p)(EG)(n)OMe layers free of unwanted residues. The protein-repellent character of these grafted layers (here, toward BSA) was studied by IR and AFM imaging. C(p)(EG)(n)OMe layers exhibit a lower surface concentration than (EG)(n)OMe layers, because of the presence of a solvent in the grafting solution; they however demonstrate high resistance against BSA adsorption for high values of the n/p ratio and a higher stability than (EG)(n)OMe. This behavior is consistently explained by the poor ordering capability of the alkyl part of the layer, contrary to what is observed for similar layers on Au, and the key role of an entangled arrangement of the ethylene oxide chains which forms when these chains are long enough. PMID:22988984

  20. 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.

  1. Probing the Nanosecond Dynamics of a Designed Three-Stranded Beta-Sheet with a Massively Parallel Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Vincent A. Voelz

    2009-03-01

    Full Text Available Recently a temperature-jump FTIR study of a designed three-stranded sheet showing a fast relaxation time of ~140 ± 20 ns was published. We performed massively parallel molecular dynamics simulations in explicit solvent to probe the structural events involved in this relaxation. While our simulations produce similar relaxation rates, the structural ensemble is broad. We observe the formation of turn structure, but only very weak interaction in the strand regions, which is consistent with the lack of strong backbone-backbone NOEs in previous structural NMR studies. These results suggest that either DPDP-II folds at time scales longer than 240 ns, or that DPDP-II is not a well-defined three-stranded β-sheet. This work also provides an opportunity to compare the performance of several popular forcefield models against one another.

  2. 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…

  3. 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...

  4. 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%.

  5. 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%.

  6. Sensitivity analysis of molecular design problem for the development of novel working fluids for power cycles

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    In recent years there is a large availability of low-temperature heat sources in different applications such as waste heat in chemical industries and refrigeration plants as well as renewable energy sources such as biomass combustion, geothermal and solar heat sources. Power cycles are an important...... technology to convert such waste heat sources into usable energy. So far the low-temperature heat is not utilized efficiently for electricity generation. To optimize the heat transfer process and the power generation, the influence of the working fluid, the cycle designs and the operating conditions is vital...... and energy balances for a pump, a condenser, a turbine and an evaporator. As regards sensitivity analysis method, a global sensitivity analysis is performed based on Morris screening to determine which change of input parameters have important effects on the net power output. The screening is composed...

  7. 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.

  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. Molecular and process design for rotavirus-like particle production in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Palomares Laura A

    2011-05-01

    Full Text Available Abstract Background Virus-like particles (VLP have an increasing range of applications including vaccination, drug delivery, diagnostics, gene therapy and nanotechnology. These developments require large quantities of particles that need to be obtained in efficient and economic processes. Production of VLP in yeast is attractive, as it is a low-cost protein producer able to assemble viral structural proteins into VLP. However, to date only single-layered VLP with simple architecture have been produced in this system. In this work, the first steps required for the production of rotavirus-like particles (RLP in S. cerevisiae were implemented and improved, in order to obtain the recombinant protein concentrations required for VLP assembly. Results The genes of the rotavirus structural proteins VP2, VP6 and VP7 were cloned in four Saccharomyces cerevisiae strains using different plasmid and promoter combinations to express one or three proteins in the same cell. Performance of the best constructs was evaluated in batch and fed-batch cultures using a complete synthetic media supplemented with leucine, glutamate and succinate. The strain used had an important effect on recombinant protein concentration, while the type of plasmid, centromeric (YCp or episomal (YEp, did not affect protein yields. Fed-batch culture of the PD.U-267 strain resulted in the highest concentration of rotavirus proteins. Volumetric and specific productivities increased 28.5- and 11-fold, respectively, in comparison with batch cultures. Expression of the three rotavirus proteins was confirmed by immunoblotting and RLP were detected using transmission electron microscopy. Conclusions We present for the first time the use of yeast as a platform to express multilayered rotavirus-like particles. The present study shows that the combined use of molecular and bioprocess tools allowed the production of triple-layered rotavirus RLP. Production of VLP with complex architecture in yeasts

  10. 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

  11. Molecular Structure of RADA16-I Designer Self-Assembling Peptide Nanofibers

    Science.gov (United States)

    Cormier, Ashley R.; Pang, Xiaodong; Zimmerman, Maxwell I.; Zhou, Huan-Xiang; Paravastu, Anant K.

    2013-01-01

    The designer self-assembling peptide RADA16-I forms nanofiber matrices which have shown great promise for regenerative medicine and 3-dimensional cell culture. RADA16-I has a β-strand-promoting alternating hydrophobic/charged motif, but arrangement of β-strands into the nanofiber structure has not been previously determined. Here we present a structural model of RADA16-I nanofibers, based on solid-state NMR measurements on samples with different schemes for 13C isotopic labeling. NMR peak positions and line widths indicate an ordered structure composed of β-strands. The NMR data show that the nanofibers are composed of two stacked β-sheets stabilized by a hydrophobic core formed by alanine sidechains, consistent with previous proposals. However, the previously proposed antiparallel β-sheet structure is ruled out by 13C-13C dipolar couplings. Instead, neighboring β-strands within β-sheets are parallel, with a registry shift that allows for cross-strand staggering of oppositely charged arginine and aspartate sidechains. The resulting structural model is compared to nanofiber dimensions observed via images taken by transmission electron microscopy and atomic force microscopy. Multiple NMR peaks for each alanine sidechain were observed and could be attributed to multiple configurations of sidechain packing within a single scheme for intermolecular packing. PMID:23977885

  12. Molecular design, synthesis and anticoagulant activity evaluation of fluorinated dabigatran analogues.

    Science.gov (United States)

    Wang, Fei; Ren, Yu-Jie; Dong, Ming-Hui

    2016-06-15

    In the present study, a series of unreported fluorinated dabigatran analogues, which were based on the structural scaffold of dabigatran, were designed by computer-aided simulation. Fifteen fluorinated dabigatran analogues were screened and synthesized. All target compounds were characterized by (1)H NMR, (13)C NMR, (19)F NMR and HRMS. According to the preliminary screening results of inhibition ratio, eleven analogues (inhibition ratio >90%) were evaluated for antithrombin activity in vitro (IC50). The test results expressed that all the analogues showed effective inhibitory activities against thrombin. Especially, compounds 8f, 8k and 8o, with IC50 values of 1.81, 3.21 and 2.16nM, respectively, showed remarkable anticoagulant activities which were in the range of reference drug dabigatran (IC50=1.23nM). Moreover, compounds 8k and 8o were developed to investigate their anticoagulant activities in vivo. In those part, compound 8o exhibited a fairly strong inhibitory action for arteriovenous thrombosis with inhibition ratio of 84.66%, which was comparable with that of dabigatran (85.07%). Docking simulations demonstrated that these compounds could act as candidates for further development of novel anticoagulant drugs.

  13. Molecular Design of TPD-based Organic Dyes for Dye-sensitized Solar Cells

    Institute of Scientific and Technical Information of China (English)

    CAO Xing-bo

    2013-01-01

    An interesitng class of organic A-π-D-π-A dyes based on an N,N,N',N'-tetraphenylbenzidine(TPD) unit as donor was designed and synthesized for dye-sensitized solar cells(DSSCs).TPD-4-based DSSCs gave a short circuit photocurrent density(Jsc) of 16.67 mA/cm2,a open circuit voltage(Voc) of 0.635 V and a fill factor(ff) of 0.68,achieving a solar-to-electricity conversion efficiency(η) of 7.22% in preliminary tests.The N3-sensitized device gave an η value of 8.02% with a Jsc of 18.81 mA/cm2,a Voc of 0.630 V and an ffof 0.68 under the same conditions.The incident photo-to-current efficiency(IPCE) values above 70% observed in a range of 460 to 600 nm with a maximum value of 80% at 500 nm indicate that the TPD-4-based DSSC shows a high performance.Under the same conditions,the DSSC based on N3 provided the IPCE values above 70% in a range of 490 to 580 nm with a maximum value of 76% at 500 nm.Both further optimization of the device processing and structural modification of these dyes are anticipated to make the device give even better performances.

  14. 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.

  15. 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

  16. 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.

  17. Ultrasound molecular imaging: Moving toward clinical translation

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K., E-mail: willmann@stanford.edu

    2015-09-15

    Highlights: • Ultrasound molecular imaging is a highly sensitive modality. • A clinical grade ultrasound contrast agent has entered first in human clinical trials. • Several new potential future clinical applications of ultrasound molecular imaging are being explored. - Abstract: Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.

  18. Design of perylene diimides for organic solar cell: Effect of molecular steric hindrance and extended conjugation

    Energy Technology Data Exchange (ETDEWEB)

    Kozma, Erika, E-mail: erika.kozma@ismac.cnr.it [Istituto per lo Studio delle Macromolecole, Consiglio Nazionale delle Ricerche, 20133 Milano (Italy); Kotowski, Dariusz; Catellani, Marinella; Luzzati, Silvia [Istituto per lo Studio delle Macromolecole, Consiglio Nazionale delle Ricerche, 20133 Milano (Italy); Cavazzini, Marco; Bossi, Alberto; Orlandi, Simonetta [Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, 20133 Milano (Italy); Bertini, Fabio [Istituto per lo Studio delle Macromolecole, Consiglio Nazionale delle Ricerche, 20133 Milano (Italy)

    2015-08-01

    Core-substituted perylene diimides (PDI) are promising candidates as n-type semiconductor materials for organic photovoltaics. The chemical functionalization of perylene diimides in the bay positions is a versatile tool to obtain a series of electron acceptor materials with tunable electron affinity. These materials usually feature a donor-acceptor D-A structure in which the electron withdrawing PDI core is covalently linked with different electron donating chemical groups. The structural and electronic properties of the substituents define and modulate the optical/electrical properties of the semiconductor and the performance as photovoltaic material. In this work we designed two PDI molecules with D-A-D structure using spirobifluorene group as substituent directly linked to the perylene core (PDI-SF) and with insertion of a bithiophene moiety (PDI-BSF). In both molecules we found a reduced tendency to form aggregates in the solid state thanks to the cross-shaped rigid structure and strong steric hindrance of the spirobifluorene group. Additionally, in the case of PDI-BSF the presence of the bithiophene linker contributes significantly to extend the conjugation, resulting in a panchromatic absorption in the whole visible to NIR region. We present the synthesis of these materials and their characterisation in terms of absorption spectroscopy, cyclic voltammetry and computational calculations. Finally we show preliminary results of their use as active components in P3HT/PDIs bulk heterojunction solar cells. - Highlights: • New D-A-D n-type materials have been synthesized. • PDI-SF and PDI-BSF were used as acceptors in organic solar cells. • Performances of 1.32% were achieved in blend with P3HT in a BHJ conventional architecture.

  19. New renewable resource amphiphilic molecular design for size-controlled and highly ordered polyaniline nanofibers.

    Science.gov (United States)

    Anilkumar, P; Jayakannan, M

    2006-06-20

    We demonstrate here, for the first time, a unique strategy for conducting polyaniline nanofibers based on renewable resources. Naturally available cardanol, which is an industrial waste and main pollutant from the cashew nut industry, is utilized for producing well-defined polyaniline nanofibers. A new amphiphilic molecule is designed and developed from cardanol, which forms a stable emulsion with aniline for a wide composition range in water (1:1 to 1:100 dopant/aniline mole ratio) to produce polyaniline nanofibers. The scanning electron microscopy and transmission electron microscopy analysis of the nanofibers reveals that the dopant/aniline ratio plays a major role in determining the shape and size of polyaniline nanofibers. The nanofiber length increases with the increase in the dopant/aniline ratio, and perfectly linear, well-defined nanofibers of lengths as long as 7-8 muM were produced. The amphiphilic dopant has a built-in head-to-tail geometry and effectively penetrates into the polyaniline chains to form highly organized nanofibers. Wide-angle X-ray diffraction (WXRD) spectra of the nanofibers showed a new peak at 2theta = 6.3 (d spacing = 13.9 A) corresponding to the three-dimensional solid-state ordering of polyaniline-dopant chains, and this peak intensity increases with increase in the nanofiber length. The comparison of morphology and WXRD reveals that high ordering in polyaniline chains results in the formation of long, well-defined nanofibers, and this direct correlation for the polyaniline nanofibers with solid-state ordering has been established. The conductivity of the polyaniline nanofibers also increases with increase in the solid-state ordering rather than increasing with the extent of doping. The polyaniline nanofibers are freely soluble in water and possess high environmental and thermal stability up to 300 degrees C for various applications. PMID:16768535

  20. Designing a SCAR molecular marker for monitoring Trichoderma cf. harzianum in experimental communities.

    Science.gov (United States)

    Pérez, Gabriel; Verdejo, Valentina; Gondim-Porto, Clarissa; Orlando, Julieta; Carú, Margarita

    2014-11-01

    Several species of the fungal genus Trichoderma establish biological interactions with various micro- and macro-organisms. Some of these interactions are relevant in ecological terms and in biotechnological applications, such as biocontrol, where Trichoderma could be considered as an invasive species that colonizes a recipient community. The success of this invasion depends on multiple factors, which can be assayed using experimental communities as study models. Therefore, the aim of this work is to develop a species-specific sequence-characterized amplified region (SCAR) marker to monitor the colonization and growth of T. cf. harzianum when it invades experimental communities. For this study, 16 randomly amplified polymorphic DNA (RAPD) primers of 10-mer were used to generate polymorphic patterns, one of which generated a band present only in strains of T. cf. harzianum. This band was cloned, sequenced, and five primers of 20-23 mer were designed. Primer pairs 2F2/2R2 and 2F2/2R3 successfully and specifically amplified fragments of 278 and 448 bp from the T. cf. harzianum BpT10a strain DNA, respectively. Both primer pairs were also tested against the DNA from 14 strains of T. cf. harzianum and several strains of different fungal genera as specificity controls. Only the DNA from the strains of T. cf. harzianum was successfully amplified. Moreover, primer pair 2F2/2R2 was assessed by quantitative real-time polymerase chain reaction (PCR) using fungal DNA mixtures and DNA extracted from fungal experimental communities as templates. T. cf. harzianum was detectable even when as few as 100 copies of the SCAR marker were available or even when its population represented only 0.1% of the whole community.

  1. Molecular Design, Structural Analysis and Antifungal Activity of Derivatives of Peptide CGA-N46.

    Science.gov (United States)

    Li, Rui-Fang; Lu, Zhi-Fang; Sun, Ya-Nan; Chen, Shi-Hua; Yi, Yan-Jie; Zhang, Hui-Ru; Yang, Shuo-Ye; Yu, Guang-Hai; Huang, Liang; Li, Chao-Nan

    2016-09-01

    Chromogranin A (CGA)-N46, a derived peptide of human chromogranin A, has antifungal activity. To further research the active domain of CGA-N46, a series of derivatives were designed by successively deleting amino acid from both terminus of CGA-N46, and the amino acid sequence of each derivative was analyzed by bioinformatic software. Based on the predicted physicochemical properties of the peptides, including half-life time in mammalian reticulocytes (in vitro), yeast (in vivo) and E. coli (in vivo), instability index, aliphatic index and grand average of hydropathicity (GRAVY), the secondary structure, net charge, the distribution of hydrophobic residues and hydrophilic residues, the final derivatives CGA-N15, CGA-N16, CGA-N12 and CGA-N8 were synthesized by solid-phase peptide synthesis. The results of bioinformatic analysis showed that CGA-N46 and its derivatives were α-helix, neutral or weak positive charge, hydrophilic, and CGA-N12 and CGA-N8 were more stable than the other derivatives. The results of circular dichroism confirmed that CGA-N46 and its derived peptides displayed α-helical structure in an aqueous solution and 30 mM sodium dodecylsulfate, but α-helical contents decreased in hydrophobic lipid vesicles. CGA-N15, CGA-N16, CGA-N12 and CGA-N8 had higher antifungal activities than their mother peptide CGA-N46. Among of the derived peptides, CGA-N12 showed the least hemolytic activity. In conclusion, we have successfully identified the active domain of CGA-N46 with strong antifungal activity and weak hemolytic activity, which provides the possibility to develop a new class of antibiotics.

  2. Use of human amelogenin in molecular encapsulation for the design of pH responsive microparticles

    Directory of Open Access Journals (Sweden)

    Bonde Johan

    2012-05-01

    Full Text Available Abstract Background Proteins can be used in drug delivery systems to improve pharmacological properties of an active substance. Differences in pH between tissues can be utilized in order to achieve a targeted drug release at a specific location or tissue, such as a tumor. The enamel matrix protein amelogenin has a pH dependent solubility profile and self-assemble to form aggregates at neutral pH. This could make amelogenin useful in the design of pH responsive drug delivery systems. Results In this study amelogenin was evaluated as a pH responsive component in drug delivery applications. This was achieved by testing the ability of amelogenin to entrap/release other proteins upon changes in pH, and by testing if amelogenin could confer pH responsiveness to an existing and versatile drug delivery system, such as gelatin microparticles. Amelogenin was able to encapsulate bovine serum albumin and insulin, whichwere used as model target proteins. The composite aggregates of amelogenin and target protein were formed at neutral pH and could be reversibly solubilized at weakly acidic pH. Gelatin microparticles prepared in the presence of amelogenin, showed a modulated structure in response to pH change, when studied by scanning electron microscopy, compared to particles without amelogenin. At neutral pH amelogenin induced formation of pores in the particle surface, which were not present at acidic pH, or in particles lacking amelogenin. Conclusions The results from this study demonstrate that amelogenin can be a useful component in drug delivery systems in order to achieve a pH dependent response.

  3. Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

    Directory of Open Access Journals (Sweden)

    Jessica L. Bell

    2013-05-01

    Full Text Available CCG-1423 and related analogues represent a new class of inhibitors of Rho/MKL1/SRF-mediated gene transcription, a pathway that has been implicated in both cancer and fibrosis. The molecular target for these compounds is unknown. To facilitate its identification, a series of tag-free photoaffinity probes was designed and synthesized, each one containing a photoactivatable group and an acetylenic end group for subsequent attachment to a fluorescent tag using click chemistry. All were confirmed to maintain biological activity in a cell-based assay for inhibition of SRE-Luc expression. The functional activity of the most potent probe 24 was further confirmed in an assay for PC-3 cell migration. Photolysis of 24 in intact PC-3 cells followed by cell lysis, click ligation of a fluorescent dye, and gel electrophoresis revealed specific labeling of a single 24 kDa band that could be blocked with an active competitor. Future work will focus on identifying the labeled protein(s.

  4. Computational design of a pH stable enzyme: understanding molecular mechanism of penicillin acylase's adaptation to alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Dmitry Suplatov

    Full Text Available Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties.

  5. Design, synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole.

    Science.gov (United States)

    Nasr, Tamer; Bondock, Samir; Eid, Sameh

    2016-01-01

    Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis and in vitro antimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound 8d was most active against Bacillis subtilis (MIC, 0.007 µg/mL). Moreover, compounds 7c-d and 8c displayed significant activities against B. subtilis and Streptococcus pneumoniae (MIC, 0.03-0.06 µg/mL and 0.06-0.12 µg/mL versus ampicillin 0.24 µg/mL and 0.12 µg/mL; respectively). Compounds 7a and 7c-d were highly potent against Escherichia coli (MIC, 0.49-0.98 µg/mL versus gentamycin 1.95 µg/mL). On the other hand, compounds 7e and 9c were fourfolds more active than amphotericin B against Syncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents.

  6. Molecular design and genetic optimization of antimicrobial peptides containing unnatural amino acids against antibiotic-resistant bacterial infections.

    Science.gov (United States)

    He, Yongkang; He, Xiaofeng

    2016-09-01

    Antimicrobial peptides (AMPs) have been the focus of intense research towards the finding of a viable alternative to current small-molecule antibiotics, owing to their commonly observed and naturally occurring resistance against pathogens. However, natural peptides have many problems such as low bioavailability and high allergenicity that largely limit the clinical applications of AMPs. In the present study, an integrative protocol that combined chemoinformatics modeling, molecular dynamics simulations, and in vitro susceptibility test was described to design AMPs containing unnatural amino acids (AMP-UAAs). To fulfill this, a large panel of synthetic AMPs with determined activity was collected and used to perform quantitative structure-activity relationship (QSAR) modeling. The obtained QSAR predictors were then employed to direct genetic algorithm (GA)-based optimization of AMP-UAA population, to which a number of commercially available, structurally diverse unnatural amino acids were introduced during the optimization process. Subsequently, several designed AMP-UAAs were confirmed to have high antibacterial potency against two antibiotic-resistant strains, i.e. multidrug-resistant Pseudomonas aeruginosa (MDRPA) and methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentration (MIC) < 10 μg/ml. Structural dynamics characterizations revealed that the most potent AMP-UAA peptide is an amphipathic helix that can spontaneously embed into an artificial lipid bilayer and exhibits a strong destructuring tendency associated with the embedding process. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 746-756, 2016.

  7. Influence of molecular design on biodistribution and targeting properties of an Affibody-fused HER2-recognising anticancer toxin.

    Science.gov (United States)

    Altai, Mohamed; Liu, Hao; Orlova, Anna; Tolmachev, Vladimir; Gräslund, Torbjörn

    2016-09-01

    Targeted delivery of toxins is a promising way to treat disseminated cancer. The use of monoclonal antibodies as targeting moiety has provided proof-of-principle for this approach. However, extravasation and tissue penetration rates of antibody-based immunotoxins are limited due to antibody bulkiness. The use of a novel class of targeting probes, Affibody molecules, provides smaller toxin-conjugated constructs, which may improve targeting. Earlier, we have demonstrated that affitoxins containing a HER2-targeting Affibody moiety and a deimmunized and truncated exotoxin A from Pseudomonas aeruginosa, PE38X8, provide highly selective toxicity to HER2-expressing cancer cells. To evaluate the influence of molecular design on targeting and biodistribution properties, a series of novel affitoxins were labelled with the residualizing radionuclide 111In. In this study, we have shown that the novel conjugates are more rapidly internalized compared with the parental affitoxin. The use of a (HE)3 purification tag instead of a hexahistidine tag enabled significant (pmolecular design of scaffold protein based anticancer targeted toxins can appreciably improve their biodistribution and targeting properties.

  8. A rational design for improving the trypsin resistance of aflatoxin-detoxifizyme (ADTZ) based on molecular structure evaluation.

    Science.gov (United States)

    Qiu, Yuxin; Wu, Xiyang; Xie, Chunfang; Hu, Yadong; Liu, Daling; Ma, Yi; Yao, Dongsheng

    2016-05-01

    The resistance of feed enzymes against proteases is crucial in livestock farming. In this study, the trypsin resistance of aflatoxin-detoxifizyme (ADTZ) is improved. ADTZ possesses 72 lys/arg residue sites, 45 of which are scattered on the outermost layers of the molecule (RSA≧25%). These 45 lys/arg sites could be target sites for trypsin hydrolysis. By considering shape-matching (including physical and secondary bond interactions) and the "induced fit-effect", we hypothesized that some of these lys/arg sites are vulnerable to trypsin. A protein-protein docking simulation method was used to avoid the massive computational requirements and to address the intricacy of selecting candidate sites, as candidate site selection is affected by space displacement. Optimal mutants (K244Q/K213C/K270T and R356E/K357T/R623C) were predicted by computational design with protein folding energy analysis and molecular dynamics simulations. A trypsin digestion assay was performed, and the mutants displayed much higher stability against trypsin hydrolysis compared to the native enzyme. Moreover, temperature- and pH-activity profiles revealed that the designed mutations did not affect the catalytic activity of the enzyme.

  9. Development of the designed ankyrin repeat protein (DARPin) G3 for HER2 molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, Robert; Livanos, Maria; Bhavsar, Gaurav; Rashid, Mohammed; Miranda, Enrique; Tolner, Berend; Meyer, Tim; Chester, Kerry [UCL Cancer Institute, London (United Kingdom); Sosabowski, Jane; Leyton, Julius; Mather, Stephen [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom); Vigor, Kim [Clare Hall Laboratories, Biotherapeutics Development Unit, Cancer Research UK, South Mimms (United Kingdom); Nagy-Davidescu, Gabriela; Plueckthun, Andreas [Universitaet Zuerich, Biochemisches Institut, Zuerich (Switzerland); Yeung, Jenny [UCL Cancer Institute, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom)

    2014-11-13

    Human epidermal growth factor receptor-2 (HER2) overexpression is a predictor of response to anti-HER2 therapy in breast and gastric cancer. Currently, HER2 status is assessed by tumour biopsy, but this may not be representative of the larger tumour mass or other metastatic sites, risking misclassification and selection of suboptimal therapy. The designed ankyrin repeat protein (DARPin) G3 binds HER2 with high affinity at an epitope that does not overlap with trastuzumab and is biologically inert. We hypothesized that radiolabelled DARPin G3 would be capable of selectively imaging HER2-positive tumours, and aimed to identify a suitable format for clinical application. G3 DARPins tagged with hexahistidine (His{sub 6}) or with histidine glutamate (HE){sub 3} and untagged G3 DARPins were manufactured using a GMP-compatible Pichia pastoris protocol and radiolabelled with {sup 125}I, or with {sup 111}In via DOTA linked to a C-terminal cysteine. BALB/c mice were injected with radiolabelled G3 and tissue biodistribution was evaluated by gamma counting. The lead construct ((HE){sub 3}-G3) was assessed in mice bearing HER2-positive human breast tumour (BT474) xenografts. For both isotopes, (HE){sub 3}-G3 had significantly lower liver uptake than His{sub 6}-G3 and untagged G3 counterparts in non-tumour-bearing mice, and there was no significantly different liver uptake between His{sub 6}-G3 and untagged G3. (HE){sub 3}-G3 was taken forward for evaluation in mice bearing HER2-positive tumour xenografts. The results demonstrated that radioactivity from {sup 111}In-(HE){sub 3}-G3 was better maintained in tumours and cleared faster from serum than radioactivity from {sup 125}I-(HE){sub 3}-G3, achieving superior tumour-to-blood ratios (343.7 ± 161.3 vs. 22.0 ± 11.3 at 24 h, respectively). On microSPECT/CT, {sup 111}In-labelled and {sup 125}I-labelled (HE){sub 3}-G3 could image HER2-positive tumours at 4 h after administration, but there was less normal tissue uptake of

  10. Unraveling the Alkaline Phosphatase Inhibition, Anticancer, and Antileishmanial Potential of Coumarin-Triazolothiadiazine Hybrids: Design, Synthesis, and Molecular Docking Analysis.

    Science.gov (United States)

    Ibrar, Aliya; Zaib, Sumera; Jabeen, Farukh; Iqbal, Jamshed; Saeed, Aamer

    2016-07-01

    A series of new coumarin-triazolothiadiazine hybrid compounds (5a-j) was designed and synthesized by using the molecular hybridization concept. The cyclocondensation reaction involves the coumarinyl 4-amino-1,2,4-triazole and a range of bromo-acetophenones, delivering the desired products in good yields. The structures of the synthesized compounds were established on the basis of spectro-analytical data. The prepared compounds were evaluated against alkaline phosphatase (ALP) where compound 5j incorporating bis-coumarinyl motifs at the 3- and 6-positions of the heteroaromatic core turned out to be a potent inhibitor with an IC50 value of 1.15 ± 1.0 µM. The synthesized compounds were also tested against Leishmania major and 5h was the lead member with an IC50 value of 0.89 ± 0.08 μM. Anticancer activity was also determined using kidney fibroblast (BHK-21) and lung carcinoma (H-157) cancer cell lines. Compound 5i showed highest cytotoxic potential against H-157 cells with an IC50 value of 1.01 ± 0.12 μM, which is an improved inhibition compared to the standards (vincristine and cisplatin) used in this assay. Molecular docking studies were carried out on the synthesized library of coumarin-triazolothiadiazine hybrids against ALP. Almost all of the compounds showed strong interactions with the key residues of the active site of the receptor. In case of compounds 5a-c, 5h, and 5j, docking results positively complemented the experimental screening. These results provided substantial evidence for the further development of these compounds as potent inhibitors of ALP.

  11. Molecular modeling of directed self-assembly of block copolymers: Fundamental studies of processing conditions and evolutionary pattern design

    Science.gov (United States)

    Khaira, Gurdaman Singh

    Rapid progress in the semi-conductor industry has pushed for smaller feature sizes on integrated electronic circuits. Current photo-lithographic techniques for nanofabrication have reached their technical limit and are problematic when printing features small enough to meet future industrial requirements. "Bottom-up'' techniques, such as the directed self-assembly (DSA) of block copolymers (BCP), are the primary contenders to compliment current "top-down'' photo-lithography ones. For industrial requirements, the defect density from DSA needs to be less than 1 defect per 10 cm by 10 cm. Knowledge of both material synthesis and the thermodynamics of the self-assembly process are required before optimal operating conditions can be found to produce results adequate for industry. The work present in this thesis is divided into three chapters, each discussing various aspects of DSA as studied via a molecular model that contains the essential physics of BCP self-assembly. Though there are various types of guiding fields that can be used to direct BCPs over large wafer areas with minimum defects, this study focuses only on chemically patterned substrates. The first chapter addresses optimal pattern design by describing a framework where molecular simulations of various complexities are coupled with an advanced optimization technique to find a pattern that directs a target morphology. It demonstrates the first ever study where BCP self-assembly on a patterned substrate is optimized using a three-dimensional description of the block-copolymers. For problems pertaining to DSA, the methodology is shown to converge much faster than the traditional random search approach. The second chapter discusses the metrology of BCP thin films using TEM tomography and X-ray scattering techniques, such as CDSAXS and GISAXS. X-ray scattering has the advantage of being able to quickly probe the average structure of BCP morphologies over large wafer areas; however, deducing the BCP morphology

  12. 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

  13. 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.

  14. 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. PMID:26441808

  15. SSZ-13 Crystallization by Particle Attachment and Deterministic Pathways to Crystal Size Control.

    Science.gov (United States)

    Kumar, Manjesh; Luo, Helen; Román-Leshkov, Yuriy; Rimer, Jeffrey D

    2015-10-14

    Many synthetic and natural crystalline materials are either known or postulated to grow via nonclassical pathways involving the initial self-assembly of precursors that serve as putative growth units for crystallization. Elucidating the pathway(s) by which precursors attach to crystal surfaces and structurally rearrange (postattachment) to incorporate into the underlying crystalline lattice is an active and expanding area of research comprising many unanswered fundamental questions. Here, we examine the crystallization of SSZ-13, which is an aluminosilicate zeolite that possesses exceptional physicochemical properties for applications in separations and catalysis (e.g., methanol upgrading to chemicals and the environmental remediation of NO(x)). We show that SSZ-13 grows by two concerted mechanisms: nonclassical growth involving the attachment of amorphous aluminosilicate particles to crystal surfaces and classical layer-by-layer growth via the incorporation of molecules to advancing steps on the crystal surface. A facile, commercially viable method of tailoring SSZ-13 crystal size and morphology is introduced wherein growth modifiers are used to mediate precursor aggregation and attachment to crystal surfaces. We demonstrate that small quantities of polymers can be used to tune crystal size over 3 orders of magnitude (0.1-20 μm), alter crystal shape, and introduce mesoporosity. Given the ubiquitous presence of amorphous precursors in a wide variety of microporous crystals, insight of the SSZ-13 growth mechanism may prove to be broadly applicable to other materials. Moreover, the ability to selectively tailor the physical properties of SSZ-13 crystals through molecular design offers new routes to optimize their performance in a wide range of commercial applications. PMID:26376337

  16. Protein mimics by attachment of cyclic peptides to molecular scaffolds

    NARCIS (Netherlands)

    van de Langemheen, W.

    2014-01-01

    The interaction between proteins is important in all biological functions. In practically every cellular process protein complexes have been identified as essential components. Defects or disturbance in the regulation of protein-protein interactions are responsible for many diseases. Therefore, the

  17. A bio-inspired design strategy: Organization of tryptophan-appended naphthalenediimide into well-defined architectures induced by molecular interactions

    Science.gov (United States)

    Avinash, M. B.; Govindaraju, T.

    2011-06-01

    The chemistry of molecular assemblies involves weak yet complex non-covalent interactions, and the molecular organization of the π-conjugated material is crucial in determining the performance of an organic electronic device. Herein we demonstrate a bioinspired design strategy to tune the self-assembly of naphthalenediimides (NDIs) by minute structural variations, π-π stacking, hydrophobic interactions and metal interactions. We address some of the limitations associated with current design strategies, such as restriction to a specific molecular interaction or the difficulty in controlling the assembly due to several complicated intermolecular interactions. Hydrophobic-effect-induced J-type aggregation and sodium-interaction-induced H-type aggregation of tryptophan-appended NDIs have been illustrated. 1H NMR spectra further reveal sodium cation-π interactions in tryptophan-appended NDIs, while NMR and IR spectroscopic studies confirm the structural variations associated with the molecular assembly. In summary, the molecular organization has been successfully transformed from nanospheres to particles, nanobelts, fibers and fractals. Such drastic changes in the morphology are clear and striking evidence of the importance of non-trivial weak non-covalent forces.The chemistry of molecular assemblies involves weak yet complex non-covalent interactions, and the molecular organization of the π-conjugated material is crucial in determining the performance of an organic electronic device. Herein we demonstrate a bioinspired design strategy to tune the self-assembly of naphthalenediimides (NDIs) by minute structural variations, π-π stacking, hydrophobic interactions and metal interactions. We address some of the limitations associated with current design strategies, such as restriction to a specific molecular interaction or the difficulty in controlling the assembly due to several complicated intermolecular interactions. Hydrophobic-effect-induced J-type aggregation

  18. Wear simulation effects on overdenture stud attachments.

    Science.gov (United States)

    Rutkunas, Vygandas; Mizutani, Hiroshi; Takahashi, Hidekazu; Iwasaki, Naohiko

    2011-01-01

    The aim of this study was to evaluate wear effects on overdenture resilient attachments. Six commercially available attachments were investigated: ERA orange and white (EO and EW), Locator pink, white and blue (LRP, LRW and LRB) and OP anchor (OP). Five specimens were used for wear simulation while other two specimens served as controls. Fifteen thousands insertion-removal cycles were simulated. Dimensional changes and surface characteristics were evaluated using light microscopy and SEM, respectively. Sudden decrease of retentive force was characteristic for EO and EW attachments. Retentive force of Locator attachments fluctuated throughout the wear simulation period. Dimensional changes and surface wear was more expressed on plastic cores than on plastic rings of attachment males. Based on SEM analysis, some of the specimens obtained smoother surface after wear simulation. Mechanism of retention loss of resilient overdenture attachments can be only partially explained by dimensional changes and surface alterations.

  19. Association Between Insecure Attachment and ADHD

    DEFF Research Database (Denmark)

    Storebo, Ole Jakob; Darling Rasmussen, Pernille; Simonsen, Erik

    2016-01-01

    Objective: Psychological theories have postulated an association between insecure attachment and ADHD. The objective of this study is to investigate possible association between insecure attachment and ADHD in children and adults. Method: Review of literature was performed using the Psyc......INFO, Medline, and EMBASE databases. Results: Twenty-nine studies were included in the review. Overall, the studies showed that parental attachment problems and environmental mediating factors were significantly associated with childhood ADHD. Adults with ADHD had a much higher incidence of insecure attachment...... styles than reported in the general population. Conclusion: There seems to be a clear association between ADHD and insecure attachment. It is likely that early intervention in the form of parent training and pharmacological treatment may prevent development of attachment problems. But such studies have...

  20. Design of a tablet computer app for facilitation of a molecular blood culture test in clinical microbiology and preliminary usability evaluation

    DEFF Research Database (Denmark)

    Samson, Lasse L.; Pape-Haugaard, Louise; Meltzer, Michelle C.;

    2016-01-01

    BCT app. The study was designed to achieve a high degree of realism as participants carried out a scenario representing the context of use for the MuxBCT app. As the MuxBCT was under development, the scenario involved the use of molecular blood culture tests similar to the MuxBCT for identification...... through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular...... and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). OBJECTIVE: The objective of the study was to describe the design...

  1. Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction.

    Science.gov (United States)

    Sangshetti, Jaiprakash N; Khan, Firoz A Kalam; Kulkarni, Abhishek A; Patil, Rajendra H; Pachpinde, Amol M; Lohar, Kishan S; Shinde, Devanand B

    2016-02-01

    In present work we have designed and synthesized total twelve novel 3-(3-(1H-indol-3-yl)-3-phenylpropanoyl)-4-hydroxy-2H-chromen-2-one derivatives 13(a-l) using Ho(3+) doped CoFe2O4 nanoparticles as catalyst and evaluated for their potential antileishmanial and antioxidant activities. The compounds 13a, 13d and 13h were found to possess significant antileishmanial activity (IC50 value=95.50, 95.00 and 99.00μg/mL, respectively) when compared to the standard sodium stibogluconate (IC50=490.00 μg/mL). The compounds 13a (IC50=12.40 μg/mL), 13d (IC50=13.49 μg/mL), 13g (IC50=13.24 μg/mL) and 13l (IC50=13.74 μg/mL) had shown good antioxidant activity when compared with standards butylated hydroxy toluene (IC50=16.5 μg/mL) and ascorbic acid (IC50=12.8 μg/mL). After performing molecular docking studies, it was found that compounds 13a and 13d had potential to inhibit pteridine reductase 1 enzyme. In silico ADME pharmacokinetic parameters had shown promising results and none of the synthesized compounds had violated Lipinski's rule of five. Thus, suggesting that compounds from the present series can serve as important gateway for the design and development of new antileishmanial as well as antioxidant agent.

  2. Fundamentals in Microalgae Harvesting: From Flocculation to Self-attachment

    Science.gov (United States)

    Cui, Yan

    was used to grow and accumulate algal cells and the cost of harvesting and drying can be simply reduced by easy algae-water separation. In order to enable the envisioned algal attachment, the third objective was to investigate the cell to substrata attachment by a thermodynamic model. Based on the theoretical analysis, when the polar surface energy of the cell is greater than that of water, cellular attachment would be more favorable on materials with higher dispersive surface energy but lower polar surface energy. If the polar surface energy of the cell is smaller than that of water, more cell attachment would be expected on materials that are higher in both dispersive and polar surface energies. The model was also validated its capability in designing, selecting, and matching algal strains and solid carrier materials to enhance cell attachment. The forth objective was to investigate the effect of surface texturing on algal attachment. It was found that surface texturing had a greater effect than surface free energy, by changing the liquid wetting behavior and real contact area. The attachment is preferred when the feature size is close to the diameter of the cell attempting to settle. Larger or smaller feature dimensions have the potential to reduce cellular attachment. The fifth objective was to study the role of carrier materials and their surface roughness in attachment. If the surface chemical composition was similar, the attachment and orientation of algal cells was found to depend on the surface average roughness, wherein rougher surfaces resulted in increased attachment. Whereas, the attachment was strongly related to surface free energy as described by the thermodynamic model if materials were chemically different.

  3. Rate coefficients for dissociative attachment and resonant electron-impact dissociation involving vibrationally excited O{sub 2} molecules

    Energy Technology Data Exchange (ETDEWEB)

    Laporta, V. [Istituto di Metodologie Inorganiche e dei Plasmi, CNR, Bari, Italy and Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom); Celiberto, R. [Dipartimento di Ingegneria Civile, Ambientale, del Territorio, Edile e di Chimica, Politecnico di Bari, Italy and Istituto di Metodologie Inorganiche e dei Plasmi, CNR, Bari (Italy); Tennyson, J. [Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom)

    2014-12-09

    Rate coefficients for dissociative electron attachment and electron-impact dissociation processes, involving vibrationally excited molecular oxygen, are presented. Analytical fits of the calculated numerical data, useful in the applications, are also provided.

  4. Emergence of tempered preferential attachment from optimization

    OpenAIRE

    D'Souza, Raissa M.; Borgs, Christian; Chayes, Jennifer T.; Berger, Noam; Kleinberg, Robert D.

    2007-01-01

    We show how preferential attachment can emerge in an optimization framework, resolving a long-standing theoretical controversy. We also show that the preferential attachment model so obtained has two novel features, saturation and viability, which have natural interpretations in the underlying network and lead to a power-law degree distribution with exponential cutoff. Moreover, we consider a generalized version of this preferential attachment model with independent saturation and viability, ...

  5. Explaining gender differences in preschoolers’ attachment style

    OpenAIRE

    Tønnessen, Ellen

    2014-01-01

    Gender has throughout most attachment literature not been considered an important factor in the development of individual differences in attachment. However, some studies on preschoolers, especially using story completion/narrative measures of attachment representations, have found prominent gender differences. The present study aims to replicate such gender differences, and to examine possible explanatory variables. This will be done by using a large community sample of preschoolers from Nor...

  6. Design, synthesis, anticoagulant activity evaluation and molecular docking studies of a class of N-ethyl dabigatran derivatives.

    Science.gov (United States)

    Ren, Weixin; Ren, Yujie; Wang, Shuai

    2016-09-14

    A class of N-ethyl dabigatran derivatives was designed based on pharmacological strategies for inhibition of thrombin activity and the structure-activity relationship studies of the previous dabigatran derivatives. Activities of these novel compounds were predicted based on CoMFA model, and most of the compounds had comparable predicted activity with dabigatran. All of screened compounds were synthesized and characterized by (1)H NMR, (13)C NMR and HRMS. Subsequently, these compounds were evaluated inhibitory activity on thrombin. Among these compounds, 9a-9e, 9h, 9l-9n and 9p exhibited comparable inhibitory activity to dabigatran (IC50 = 1.20 nM), additionally, compound 9p (IC50 = 0.96 nM) exhibited better inhibitory activity than dabigatran. Moreover, compound 9p also exhibited a fairly good inhibitory activity for arteriovenous thrombosis with inhibition rate of (85.35 ± 0.72) %, which was comparable to that of dabigatran (85.07 ± 0.61) %. These results, along with related molecular docking studies, could provide an important basis for further development of compound 9p as a potent thrombin inhibitor.

  7. Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.

    Science.gov (United States)

    Abd El-Karim, Somaia S; Anwar, Manal M; Mohamed, Neama A; Nasr, Tamer; Elseginy, Samia A

    2015-12-01

    This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00-2.71μM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10μM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiís rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor.

  8. Design of Acceptors with Suitable Frontier Molecular Orbitals to Match Donors via Substitutions on Perylene Diimide for Organic Solar Cells.

    Science.gov (United States)

    Lv, Xiaoli; Li, Zhuoxin; Li, Songyang; Luan, Guoyou; Liang, Dadong; Tang, Shanshan; Jin, Ruifa

    2016-05-13

    A series of perylene diimide (PDI) derivatives have been investigated at the CAM-B3LYP/6-31G(d) and the TD-B3LYP/6-31+G(d,p) levels to design solar cell acceptors with high performance in areas such as suitable frontier molecular orbital (FMO) energies to match oligo(thienylenevinylene) derivatives and improved charge transfer properties. The calculated results reveal that the substituents slightly affect the distribution patterns of FMOs for PDI-BI. The electron withdrawing group substituents decrease the FMO energies of PDI-BI, and the electron donating group substituents slightly affect the FMO energies of PDI-BI. The di-electron withdrawing group substituents can tune the FMOs of PDI-BI to be more suitable for the oligo(thienylenevinylene) derivatives. The electron withdrawing group substituents result in red shifts of absorption spectra and electron donating group substituents result in blue shifts for PDI-BI. The -CN substituent can improve the electron transport properties of PDI-BI. The -CH₃ group in different positions slightly affects the electron transport properties of PDI-BI.

  9. M118--a rationally engineered low-molecular-weight heparin designed specifically for the treatment of acute coronary syndromes.

    Science.gov (United States)

    Kishimoto, Takashi Kei; Qi, Yi Wei; Long, Alison; Capila, Ishan; Sasisekharan, Ram; Guerrero, Luis; Fier, Ian; Roach, James; Venkataraman, Ganesh

    2009-11-01

    The initial choice of anticoagulant therapy administered in emergency departments for acute coronary syndromes (ACS) has important consequences for subsequent patient care, as neither unfractionated heparin (UFH) nor low-molecular-weight heparin (LMWH) are ideally suited for all potential clinical treatment pathways. UFH remains widely used for surgical interventions because of the ability to rapidly reverse its anticoagulant activity. However, the unpredictable pharmacokinetic profile of UFH presents safety issues, and the low subcutaneous bioavailability limits the utility of UFH for patients who are medically managed. LMWH has superior pharmacokinetic properties, but its anticoagulant activity cannot be effectively monitored or reversed during surgery. There is an unmet medical need for a baseline anticoagulant therapy that addresses these shortcomings while retaining the beneficial properties of both UFH and LMWH. We describe here M118, a novel LMWH designed specifically for use in the treatment of ACS. M118 shows broad anticoagulant activity, including potent activity against both factor Xa (~240 IU/mg) and thrombin (factor IIa; ~170 IU/mg), low polydispersity, high (78%) subcutaneous bioavailability in rabbits, and predictable subcutaneous and intravenous pharmacokinetics. Additionally, the anticoagulant activity of M118 is monitorable by standard coagulation assays and is reversible with protamine. M118 demonstrates superior activity to conventional LMWH in a rabbit model of abdominal arterial thrombosis without increasing bleeding risk, and is currently being evaluated in a phase II clinical trial evaluating efficacy and safety in patients undergoing percutaneous coronary intervention. PMID:19888526

  10. Strigolactone Analogs as Molecular Probes in Chasing the (SLs) Receptor/s: Design and Synthesis of Fluorescent Labeled Molecules

    Institute of Scientific and Technical Information of China (English)

    Cristina Prandi; Helèna Rosso; Beatrice Lace; Ernesto G. Occhiato; Alberto Oppedisano; Silvia Tabasso; Gabriele Alberto

    2013-01-01

    Originally identified as allelochemicals involved in plant-parasite interactions,more recently,Strigolactones (SLs) have been shown to play multiple key roles in the rhizosphere communication between plants and mycorrhizal fungi.Even more recent is the hormonal role ascribed to SLs which broadens the biological impact of these relatively simple molecules.In spite of the crucial and multifaceted biological role of SLs,there are no data on the receptor(s) which bind(s) such active molecules,neither in the producing plants nor in parasitic weeds or AM fungi.Information about the putative receptor of SLs can be gathered by means of structural,molecular,and genetic approaches.Our contribution on this topic is the design and synthesis of fluorescent labeled SL analogs to be used as probes for the detection in vivo of the receptor(s).Knowledge of the putative receptor structure will boost the research on analogs of the natural substrates as required for agricultural applications.

  11. A molecular design principle of lyotropic liquid-crystalline conjugated polymers with directed alignment capability for plastic electronics.

    Science.gov (United States)

    Kim, Bong-Gi; Jeong, Eun Jeong; Chung, Jong Won; Seo, Sungbaek; Koo, Bonwon; Kim, Jinsang

    2013-07-01

    Conjugated polymers with a one-dimensional p-orbital overlap exhibit optoelectronic anisotropy. Their unique anisotropic properties can be fully realized in device applications only when the conjugated chains are aligned. Here, we report a molecular design principle of conjugated polymers to achieve concentration-regulated chain planarization, self-assembly, liquid-crystal-like good mobility and non-interdigitated side chains. As a consequence of these intra- and intermolecular attributes, chain alignment along an applied flow field occurs. This liquid-crystalline conjugated polymer was realized by incorporating intramolecular sulphur-fluorine interactions and bulky side chains linked to a tetrahedral carbon having a large form factor. By optimizing the polymer concentration and the flow field, we could achieve a high dichroic ratio of 16.67 in emission from conducting conjugated polymer films. Two-dimensional grazing-incidence X-ray diffraction was performed to analyse a well-defined conjugated polymer alignment. Thin-film transistors built on highly aligned conjugated polymer films showed more than three orders of magnitude faster carrier mobility along the conjugated polymer alignment direction than the perpendicular direction.

  12. n-type doping through tethered functionality: a new paradigm for molecular design of solution-processed organic thermoelectrics

    Science.gov (United States)

    Russ, Boris; Robb, Maxwell J.; Popere, Bhooshan C.; Perry, Erin E.; Urban, Jeffrey J.; Chabinyc, Michael L.; Hawker, Craig J.; Segalman, Rachel A.

    2015-03-01

    A scarcity of stable n-type doping mechanisms compatible with facile processing has been a major impediment to the advancement of n-type (electron transporting) organic thermoelectric materials. We recently demonstrated that trimethylammonium functionalization with hydroxide counterions, tethered to a perylene diimide core by alkyl spacers, facilitated solution-processing and resulted in extremely high carrier concentrations (1020carriers/cm3) and best-in-class thermoelectric performance in thin films. In this presentation, we report our recent findings on the underlying mechanism enabling charge carrier generation in these self-doping materials and its influence on material thermoelectric behavior. To draw these conclusions, we complement thermoelectric characterization with insights into chemical, electronic, and structural properties from XPS, optical spectroscopy, EPR, and GIWAXS experiments. Furthermore, we show that doping through tethered functionality can be extended to other n-type small molecule systems of interest, including naphthalene diimides and diketopyrrolopyrroles. Our findings help shape promising molecular design strategies for future enhancements in n-type thermoelectric performance.

  13. Fabrication of an electrochemical sensor based on computationally designed molecularly imprinted polymer for the determination of mesalamine in real samples

    Energy Technology Data Exchange (ETDEWEB)

    Torkashvand, M. [Department of Analytical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Gholivand, M.B., E-mail: mbgholivand@yahoo.com [Department of Analytical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Taherkhani, F. [Department of Physical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of)

    2015-10-01

    A novel electrochemical sensor based on mesalamine molecularly imprinted polymer (MIP) film on a glassy carbon electrode was fabricated. Density functional theory (DFT) in gas and solution phases was developed to study the intermolecular interactions in the pre-polymerization mixture and to find the suitable functional monomers in MIP preparation. On the basis of computational results, o-phenylenediamine (OP), gallic acid (GA) and p-aminobenzoic acid (ABA) were selected as functional monomers. The MIP film was cast on glassy carbon electrode by electropolymerization of solution containing ternary monomers and then followed by Ag dendrites (AgDs) with nanobranch deposition. The surface feature of the modified electrode (AgDs/MIP/GCE) was characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimal experimental conditions, the peak current was proportional to the concentration of mesalamine ranging from 0.05 to 100 μM, with the detection limit of 0.015 μM. The proposed sensor was applied successfully for mesalamine determination in real samples. - Highlights: • The determination of MES using AgDs/MIP/GCE is reported for the first time. • The computer assisted design of terpolymer MIPs was used to screen monomers. • Theoretical results of DFT approach were in agreement with experimental results. • The sensor displayed a high selectivity for template in the presence of interferes. • The developed sensor has been applied to determine mesalamine in real samples.

  14. Positron-molecule interactions: resonant attachment, annihilation, and bound states

    CERN Document Server

    Gribakin, G F; Surko, C M; 10.1103/RevModPhys.82.2557

    2010-01-01

    This article presents an overview of current understanding of the interaction of low-energy positrons with molecules with emphasis on resonances, positron attachment and annihilation. Annihilation rates measured as a function of positron energy reveal the presence of vibrational Feshbach resonances (VFR) for many polyatomic molecules. These resonances lead to strong enhancement of the annihilation rates. They also provide evidence that positrons bind to many molecular species. A quantitative theory of VFR-mediated attachment to small molecules is presented. It is tested successfully for selected molecules (e.g., methyl halides and methanol) where all modes couple to the positron continuum. Combination and overtone resonances are observed and their role is elucidated. In larger molecules, annihilation rates from VFR far exceed those explicable on the basis of single-mode resonances. These enhancements increase rapidly with the number of vibrational degrees of freedom. While the details are as yet unclear, intr...

  15. Crystallization by Particle Attachment in Synthetic, Biogenic, and Geologic Environments

    Energy Technology Data Exchange (ETDEWEB)

    De Yoreo, James J.; Gilbert, Pupa U.; Sommerdijk, Nico; Penn, R. Lee; Whitelam, Stephen B.; Joester, Derk; Zhang, Hengzhong; Rimer, Jeffrey D.; Navrotsky, Alexandra; Banfield, Jillian F.; Wallace, Adam F.; Michel, F. M.; Meldrum, Fiona C.; Colfen, Helmut; Dove, Patricia M.

    2015-07-31

    Field and laboratory observations show that crystals commonly form by the addition and attachment of particles that range from multi-ion complexes to fully formed nanoparticles. These non-classical pathways to crystallization are diverse, in contrast to classical models that consider the addition of monomeric chemical species. We review progress toward understanding crystal growth by particle attachment processes and show that multiple pathways result from the interplay of free energy landscapes and reaction dynamics. Much remains unknown about the fundamental aspects; particularly the relationships between solution structure, interfacial forces, and particle motion. Developing a predictive description that connects molecular details to ensemble behavior will require revisiting long-standing interpretations of crystal formation in synthetic systems and patterns of mineralization in natural environments.

  16. A conserved haem redox and trafficking pathway for cofactor attachment

    Science.gov (United States)

    Richard-Fogal, Cynthia L; Frawley, Elaine R; Bonner, Eric R; Zhu, Huifen; San Francisco, Brian; Kranz, Robert G

    2009-01-01

    A pathway for cytochrome c maturation (Ccm) in bacteria, archaea and eukaryotes (mitochondria) requires the genes encoding eight membrane proteins (CcmABCDEFGH). The CcmABCDE proteins are proposed to traffic haem to the cytochrome c synthetase (CcmF/H) for covalent attachment to cytochrome c by unknown mechanisms. For the first time, we purify pathway complexes with trapped haem to elucidate the molecular mechanisms of haem binding, trafficking and redox control. We discovered an early step in trafficking that involves oxidation of haem (to Fe3+), yet the final attachment requires reduced haem (Fe2+). Surprisingly, CcmF is a cytochrome b with a haem never before realized, and in vitro, CcmF functions as a quinol:haem oxidoreductase. Thus, this ancient pathway has conserved and orchestrated mechanisms for trafficking, storing and reducing haem, which assure its use for cytochrome c synthesis even in limiting haem (iron) environments and reducing haem in oxidizing environments. PMID:19629033

  17. Attachment theory: Old and new approach

    Directory of Open Access Journals (Sweden)

    Polovina Nada

    2005-01-01

    Full Text Available The article is an attempt to present holistically the key concepts of attachment theory rediscovered for its potentials. The presented concepts include: narrow definition of attachment, behavioral control system of attachment, attachment working model and patterns of attachment. The concepts are presented in the context of child attachment theory and adult attachment theory, in addition to description of the development of attachment. Concepts, as well as developmental processes are presented from the stand point of pioneers in this field (John Bowlby and Mary Ainsworth as well as from the standpoint of their successors (Everett Waters and Malcolm West. Compacted ness of the theory, possibilities for operationalization of its key concepts and its application to empirical studies of complex psychological issues that have never been scientifically explored, makes it a very prospective theory in view of possible integration of existing research findings and initiating new research and new practices in psychotherapy, social work and work in schools. The goal of this integral presentation of attachment theory is to highlight its benefits and possibilities for understanding and research complex field of human's psychosocial functioning.

  18. Sine-Bar Attachment For Machine Tools

    Science.gov (United States)

    Mann, Franklin D.

    1988-01-01

    Sine-bar attachment for collets, spindles, and chucks helps machinists set up quickly for precise angular cuts that require greater precision than provided by graduations of machine tools. Machinist uses attachment to index head, carriage of milling machine or lathe relative to table or turning axis of tool. Attachment accurate to 1 minute or arc depending on length of sine bar and precision of gauge blocks in setup. Attachment installs quickly and easily on almost any type of lathe or mill. Requires no special clamps or fixtures, and eliminates many trial-and-error measurements. More stable than improvised setups and not jarred out of position readily.

  19. Overdenture locator attachments for atrophic mandible.

    Science.gov (United States)

    Mahajan, Neerja; Thakkur, Rahul K

    2013-10-01

    Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40° of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction.

  20. Overdenture locator attachments for atrophic mandible

    Directory of Open Access Journals (Sweden)

    Neerja Mahajan

    2013-01-01

    Full Text Available Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40΀ of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction.