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Sample records for bases moleculares del

  1. Cyclodextrin-based molecular machines.

    PubMed

    Hashidzume, Akihito; Yamaguchi, Hiroyasu; Harada, Akira

    2014-01-01

    This chapter overviews molecular machines based on cyclodextrins (CDs). The categories of CD-based molecular machines, external stimuli for CD-based molecular machines, and typical examples of CD-based molecular machines are briefly described.

  2. The R215W mutation in NBS1 impairs {gamma}-H2AX binding and affects DNA repair: molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage syndrome patients

    SciTech Connect

    Masi, Alessandra di Viganotti, Mara; Polticelli, Fabio; Ascenzi, Paolo; Tanzarella, Caterina; Antoccia, Antonio

    2008-05-09

    Nijmegen breakage syndrome (NBS) is a genetic disorder characterized by chromosomal instability and hypersensitivity to ionising radiation. Compound heterozygous 657del5/R215W NBS patients display a clinical phenotype more severe than the majority of NBS patients homozygous for the 657del5 mutation. The NBS1 protein, mutated in NBS patients, contains a FHA/BRCT domain necessary for the DNA-double strand break (DSB) damage response. Recently, a second BRCT domain has been identified, however, its role is still unknown. Here, we demonstrate that the R215W mutation in NBS1 impairs histone {gamma}-H2AX binding after induction of DNA damage, leading to a delay in DNA-DSB rejoining. Molecular modelling reveals that the 215 residue of NBS1 is located between the two BRCT domains, affecting their relative orientation that appears critical for {gamma}-H2AX binding. Present data represent the first evidence for the role of NBS1 tandem BRCT domains in {gamma}-H2AX recognition, and could explain the severe phenotype observed in 657del5/R215W NBS patients.

  3. Hydantoin-based molecular photoswitches.

    PubMed

    Martínez-López, David; Yu, Meng-Long; García-Iriepa, Cristina; Campos, Pedro J; Frutos, Luis Manuel; Golen, James A; Rasapalli, Sivappa; Sampedro, Diego

    2015-04-17

    A new family of molecular photoswitches based on arylidenehydantoins is described together with their synthesis and photochemical and photophysical studies. A series of hydantoin derivatives have been prepared as single isomers using simple and versatile chemistry in good yields. Our studies show that the photostationary states of these compounds can be easily controlled by means of external factors, such as the light source or filters. Moreover, the detailed investigations proved that these switches are efficient (i.e., they make efficient use of the light energy, are high fatigue resistant, and are very photostable). In some cases, the switches can be completely turned on/off, a desirable feature for specific applications. A series of theoretical calculations have also been carried out to understand the photoisomerization mechanism at the molecular level. PMID:25806596

  4. Carbon Nanotube Based Molecular Electronics

    NASA Technical Reports Server (NTRS)

    Srivastava, Deepak; Saini, Subhash; Menon, Madhu

    1998-01-01

    Carbon nanotubes and the nanotube heterojunctions have recently emerged as excellent candidates for nanoscale molecular electronic device components. Experimental measurements on the conductivity, rectifying behavior and conductivity-chirality correlation have also been made. While quasi-one dimensional simple heterojunctions between nanotubes with different electronic behavior can be generated by introduction of a pair of heptagon-pentagon defects in an otherwise all hexagon graphene sheet. Other complex 3- and 4-point junctions may require other mechanisms. Structural stability as well as local electronic density of states of various nanotube junctions are investigated using a generalized tight-binding molecular dynamics (GDBMD) scheme that incorporates non-orthogonality of the orbitals. The junctions investigated include straight and small angle heterojunctions of various chiralities and diameters; as well as more complex 'T' and 'Y' junctions which do not always obey the usual pentagon-heptagon pair rule. The study of local density of states (LDOS) reveal many interesting features, most prominent among them being the defect-induced states in the gap. The proposed three and four pointjunctions are one of the smallest possible tunnel junctions made entirely of carbon atoms. Furthermore the electronic behavior of the nanotube based device components can be taylored by doping with group III-V elements such as B and N, and BN nanotubes as a wide band gap semiconductor has also been realized in experiments. Structural properties of heteroatomic nanotubes comprising C, B and N will be discussed.

  5. Molecular memory based on nanowire-molecular wire heterostructures.

    PubMed

    Li, Chao; Lei, Bo; Fan, Wendy; Zhang, Daihua; Meyyappan, M; Zhou, Chongwu

    2007-01-01

    This article reviews the recent research of molecular memory based on self-assembled nanowire-molecular wire heterostructures. These devices exploit a novel concept of using redox-active molecules as charge storage flash nodes for nanowire transistors, and thus boast many advantages such as room-temperature processing and nanoscale device area. Various key elements of this technology will be reviewed, including the synthesis of the nanowires and molecular wires, and fabrication and characterization of the molecular memory devices. In particular, multilevel memory has been demonstrated using In2O3 nanowires with self-assembled Fe-bis(terpyridine) molecules, which serve to multiple the charge storage density without increasing the device size. Furthermore, in-depth studies on memory devices made with different molecules or with different functionalization techniques will be reviewed and analyzed. These devices represent a conceptual breakthrough in molecular memory and may work as building blocks for future beyond-CMOS nanoelectronic circuits.

  6. Interference-based molecular transistors

    PubMed Central

    Li, Ying; Mol, Jan A.; Benjamin, Simon C.; Briggs, G. Andrew D.

    2016-01-01

    Molecular transistors have the potential for switching with lower gate voltages than conventional field-effect transistors. We have calculated the performance of a single-molecule device in which there is interference between electron transport through the highest occupied molecular orbital and the lowest unoccupied molecular orbital of a single molecule. Quantum interference results in a subthreshold slope that is independent of temperature. For realistic parameters the change in gate potential required for a change in source-drain current of two decades is 20 mV, which is a factor of six smaller than the theoretical limit for a metal-oxide-semiconductor field-effect transistor. PMID:27646692

  7. Interference-based molecular transistors.

    PubMed

    Li, Ying; Mol, Jan A; Benjamin, Simon C; Briggs, G Andrew D

    2016-01-01

    Molecular transistors have the potential for switching with lower gate voltages than conventional field-effect transistors. We have calculated the performance of a single-molecule device in which there is interference between electron transport through the highest occupied molecular orbital and the lowest unoccupied molecular orbital of a single molecule. Quantum interference results in a subthreshold slope that is independent of temperature. For realistic parameters the change in gate potential required for a change in source-drain current of two decades is 20 mV, which is a factor of six smaller than the theoretical limit for a metal-oxide-semiconductor field-effect transistor. PMID:27646692

  8. [Molecular bases of prion diseases].

    PubMed

    Pokrovskiĭ, V I; Kiselev, O I

    1998-01-01

    The paper briefly analyzes the origin of priones and their association with the cellular gene and homologous protein of diseases in man and animals. There is evidence for a direct relationship of the agents that cause spongious encephalitis in the cattle and a new type of Creutzfeldt-Jacob disease in man. The molecular organization of priones and the conformational cellular protein changes underlying the infectious activation of the cell homologue of priones. Emphasis is first laid on the capacity of the cell homologue of priones and their infectiously active derivative to bind to DNA or RNA. In the context of concepts of the priones yeasts an attempt was made to explain the reproduction through the altered control of translation of mRNA that encodes the cellular homologue of priones, which accounts for the duration of the incubation period of the disease. The infections caused by priones are referred to as the so-called slow infections. But in the context of the proposed hypothesis, an infective process in the tissues did not really have some typical signs of infection and resembles accumulation diseases more without the replicative burst typical of infectious processes. The paper gives data on the vital cycle of priones in infected animals and changes in the accumulation of an infective agent. This assesses the currently available diagnostic methods and gives preference to the methods which will be based on the use of monoclonal antibodies that specifically recognize the conformationally altered form of an infectious prione or on the identification of primary oligomeric forms which manifest the onset of amyloidization of the damaged tissues. The main conclusion of the paper is that protein prionization is a common biological phenomenon and the diseases caused by these processes will increase in number in the near future, which makes it necessary to develop diagnostic methods and universal treatments of diseases, such as bacterial infections by using antibiotics.

  9. Niobate-based octahedral molecular sieves

    DOEpatents

    Nenoff, Tina M.; Nyman, May D.

    2006-10-17

    Niobate-based octahedral molecular sieves having significant activity for multivalent cations and a method for synthesizing such sieves are disclosed. The sieves have a net negatively charged octahedral framework, comprising niobium, oxygen, and octahedrally coordinated lower valence transition metals. The framework can be charge balanced by the occluded alkali cation from the synthesis method. The alkali cation can be exchanged for other contaminant metal ions. The ion-exchanged niobate-based octahedral molecular sieve can be backexchanged in acidic solutions to yield a solution concentrated in the contaminant metal. Alternatively, the ion-exchanged niobate-based octahedral molecular sieve can be thermally converted to a durable perovskite phase waste form.

  10. Niobate-based octahedral molecular sieves

    DOEpatents

    Nenoff, Tina M.; Nyman, May D.

    2003-07-22

    Niobate-based octahedral molecular sieves having significant activity for multivalent cations and a method for synthesizing such sieves are disclosed. The sieves have a net negatively charged octahedral framework, comprising niobium, oxygen, and octahedrally coordinated lower valence transition metals. The framework can be charge balanced by the occluded alkali cation from the synthesis method. The alkali cation can be exchanged for other contaminant metal ions. The ion-exchanged niobate-based octahedral molecular sieve can be backexchanged in acidic solutions to yield a solution concentrated in the contaminant metal. Alternatively, the ion-exchanged niobate-based octahedral molecular sieve can be thermally converted to a durable perovskite phase waste form.

  11. Coordination-Cluster-Based Molecular Magnetic Refrigerants.

    PubMed

    Zhang, Shaowei; Cheng, Peng

    2016-08-01

    Coordination polymers serving as molecular magnetic refrigerants have been attracting great interest. In particular, coordination cluster compounds that demonstrate their apparent advantages on cryogenic magnetic refrigerants have attracted more attention in the last five years. Herein, we mainly focus on depicting aspects of syntheses, structures, and magnetothermal properties of coordination clusters that serve as magnetic refrigerants on account of the magnetocaloric effect. The documented molecular magnetic refrigerants are classified into two primary categories according to the types of metal centers, namely, homo- and heterometallic clusters. Every section is further divided into several subgroups based on the metal nuclearity and their dimensionalities, including discrete molecular clusters and those with extended structures constructed from molecular clusters. The objective is to present a rough overview of recent progress in coordination-cluster-based molecular magnetic refrigerants and provide a tutorial for researchers who are interested in the field. PMID:27381662

  12. FRET-based Molecular Tension Microscopy.

    PubMed

    Gayrard, Charlène; Borghi, Nicolas

    2016-02-01

    Cells generate and experience mechanical forces that may shape tissues and regulate signaling pathways in a variety of physiological or pathological situations. How forces propagate and transduce signals at the molecular level is poorly understood. The advent of FRET-based Molecular Tension Microscopy now allows to achieve mechanical force measurements at a molecular scale with molecular specificity in situ, and thereby better understand the mechanical architecture of cells and tissues, and mechanotransduction pathways. In this review, we will first expose the basic principles of FRET-based MTM and its various incarnations. We will describe different ways of measuring FRET, their advantages and drawbacks. Then, throughout the range of proteins of interest, cells and organisms to which it has been applied, we will review the tests developed to validate the approach, how molecular tension was related to cell functions, and conclude with possible developments and offshoots.

  13. Molecular bases of protein halotolerance.

    PubMed

    Graziano, Giuseppe; Merlino, Antonello

    2014-04-01

    Halophilic proteins are stable and function at high salt concentration. Understanding how these molecules maintain their fold stable and avoid aggregation under harsh conditions is of great interest for biotechnological applications. This mini-review describes what is known about the molecular determinants of protein halotolerance. Comparisons between the sequences of halophilic/non-halophilic homologous protein pairs indicated that Asp and Glu are significantly more frequent, while Lys, Ile and Leu are less frequent in halophilic proteins. Homologous halophilic and non-halophilic proteins have similar overall structure, secondary structure content, and number of residues involved in the formation of H-bonds. On the other hand, on the halophilic protein surface, a decrease of nonpolar residues and an increase of charged residues are observed. Particularly, halophilic adaptation correlates with an increase of Asp and Glu, compensated by a decrease of basic residues, mainly Lys, on protein surface. A thermodynamic model, that provides a reliable explanation of the salt effect on the conformational stability of globular proteins, is presented.

  14. Carbon-based ion and molecular channels

    NASA Astrophysics Data System (ADS)

    Sint, Kyaw; Wang, Boyang; Kral, Petr

    2008-03-01

    We design ion and molecular channels based on layered carboneous materials, with chemically-functionalized pore entrances. Our molecular dynamics simulations demonstrate that these ultra-narrow pores, with diameters around 1 nm, are highly selective to the charges and sizes of the passing (Na^+ and Cl^-) ions and short alkanes. We demonstrate that the molecular flows through these pores can be easily controlled by electrical and mechanical means. These artificial pores could be integrated in fluidic nanodevices and lab-on-a-chip techniques with numerous potential applications. [1] Kyaw Sint, Boyang Wang and Petr Kral, submitted. [2] Boyang Wang and Petr Kral, JACS 128, 15984 (2006).

  15. Ultrathin inorganic molecular nanowire based on polyoxometalates

    PubMed Central

    Zhang, Zhenxin; Murayama, Toru; Sadakane, Masahiro; Ariga, Hiroko; Yasuda, Nobuhiro; Sakaguchi, Norihito; Asakura, Kiyotaka; Ueda, Wataru

    2015-01-01

    The development of metal oxide-based molecular wires is important for fundamental research and potential practical applications. However, examples of these materials are rare. Here we report an all-inorganic transition metal oxide molecular wire prepared by disassembly of larger crystals. The wires are comprised of molybdenum(VI) with either tellurium(IV) or selenium(IV): {(NH4)2[XMo6O21]}n (X=tellurium(IV) or selenium(IV)). The ultrathin molecular nanowires with widths of 1.2 nm grow to micrometre-scale crystals and are characterized by single-crystal X-ray analysis, Rietveld analysis, scanning electron microscopy, X-ray photoelectron spectroscopy, ultraviolet–visible spectroscopy, thermal analysis and elemental analysis. The crystals can be disassembled into individual molecular wires through cation exchange and subsequent ultrasound treatment, as visualized by atomic force microscopy and transmission electron microscopy. The ultrathin molecular wire-based material exhibits high activity as an acid catalyst, and the band gap of the molecular wire-based crystal is tunable by heat treatment. PMID:26139011

  16. Bioassays Based on Molecular Nanomechanics

    PubMed Central

    Majumdar, Arun

    2002-01-01

    Recent experiments have shown that when specific biomolecular interactions are confined to one surface of a microcantilever beam, changes in intermolecular nanomechanical forces provide sufficient differential torque to bend the cantilever beam. This has been used to detect single base pair mismatches during DNA hybridization, as well as prostate specific antigen (PSA) at concentrations and conditions that are clinically relevant for prostate cancer diagnosis. Since cantilever motion originates from free energy change induced by specific biomolecular binding, this technique is now offering a common platform for label-free quantitative analysis of protein-protein binding, DNA hybridization DNA-protein interactions, and in general receptor-ligand interactions. Current work is focused on developing “universal microarrays” of microcantilever beams for high-throughput multiplexed bioassays. PMID:12590170

  17. Bioassays Based on Molecular Nanomechanics

    DOE PAGESBeta

    Majumdar, Arun

    2002-01-01

    Recent experiments have shown that when specific biomolecular interactions are confined to one surface of a microcantilever beam, changes in intermolecular nanomechanical forces provide sufficient differential torque to bend the cantilever beam. This has been used to detect single base pair mismatches during DNA hybridization, as well as prostate specific antigen (PSA) at concentrations and conditions that are clinically relevant for prostate cancer diagnosis. Since cantilever motion originates from free energy change induced by specific biomolecular binding, this technique is now offering a common platform for label-free quantitative analysis of protein-protein binding, DNA hybridization DNA-protein interactions, and in general receptor-ligandmore » interactions. Current work is focused on developing “universal microarrays” of microcantilever beams for high-throughput multiplexed bioassays.« less

  18. [Molecular based targets and endometrial cancer].

    PubMed

    Stoyanov, St; Ananiev, J; Ivanova, K; Velev, V; Todorova, M; Gulubova, M

    2015-01-01

    In recent years, increasing attention has been paid to the rate of spread of endometrial carcinoma, especially in the postmenopausal period. Along with routine diagnostic methods, giving information on the location and progression of the disease, there are some morphological methods determining very accurately the correlations in the development of this type of cancer and his prognosis. Moreover--in recent years, the accumulated information about the molecular profile of this type of cancer made it possible to implement a number of new drugs against the so-called molecular therapy -'targets' in the neoplastic process. Significant proportion of cases show response rates, it is more hope in the development of more successful formulas and target -based therapy. In this review, we present and discuss the role of certain molecular markers as potential indicators of prognosis and development, as well as determining the target treatment of endometrial carcinoma.

  19. [Molecular based targets and endometrial cancer].

    PubMed

    Stoyanov, St; Ananiev, J; Ivanova, K; Velev, V; Todorova, M; Gulubova, M

    2015-01-01

    In recent years, increasing attention has been paid to the rate of spread of endometrial carcinoma, especially in the postmenopausal period. Along with routine diagnostic methods, giving information on the location and progression of the disease, there are some morphological methods determining very accurately the correlations in the development of this type of cancer and his prognosis. Moreover--in recent years, the accumulated information about the molecular profile of this type of cancer made it possible to implement a number of new drugs against the so-called molecular therapy -'targets' in the neoplastic process. Significant proportion of cases show response rates, it is more hope in the development of more successful formulas and target -based therapy. In this review, we present and discuss the role of certain molecular markers as potential indicators of prognosis and development, as well as determining the target treatment of endometrial carcinoma. PMID:25909140

  20. Graph-based molecular alignment (GMA).

    PubMed

    Marialke, J; Körner, R; Tietze, S; Apostolakis, Joannis

    2007-01-01

    We describe a combined 2D/3D approach for the superposition of flexible chemical structures, which is based on recent progress in the efficient identification of common subgraphs and a gradient-based torsion space optimization algorithm. The simplicity of the approach is reflected in its generality and computational efficiency: the suggested approach neither requires precalculated statistics on the conformations of the molecules nor does it make simplifying assumptions on the topology of the molecules being compared. Furthermore, graph-based molecular alignment produces alignments that are consistent with the chemistry of the molecules as well as their general structure, as it depends on both the local connectivities between atoms and the overall topology of the molecules. We validate this approach on benchmark sets taken from the literature and show that it leads to good results compared to computationally and algorithmically more involved methods. The results suggest that, for most practical purposes, graph-based molecular alignment is a viable alternative to molecular field alignment with respect to structural superposition and leads to structures of comparable quality in a fraction of the time. PMID:17381175

  1. Photoswitchable gel assembly based on molecular recognition.

    PubMed

    Yamaguchi, Hiroyasu; Kobayashi, Yuichiro; Kobayashi, Ryosuke; Takashima, Yoshinori; Hashidzume, Akihito; Harada, Akira

    2012-01-03

    The formation of effective and precise linkages in bottom-up or top-down processes is important for the development of self-assembled materials. Self-assembly through molecular recognition events is a powerful tool for producing functionalized materials. Photoresponsive molecular recognition systems can permit the creation of photoregulated self-assembled macroscopic objects. Here we demonstrate that macroscopic gel assembly can be highly regulated through photoisomerization of an azobenzene moiety that interacts differently with two host molecules. A photoregulated gel assembly system is developed using polyacrylamide-based hydrogels functionalized with azobenzene (guest) or cyclodextrin (host) moieties. Reversible adhesion and dissociation of the host gel from the guest gel may be controlled by photoirradiation. The differential affinities of α-cyclodextrin or β-cyclodextrin for the trans-azobenzene and cis-azobenzene are employed in the construction of a photoswitchable gel assembly system.

  2. Photoswitchable gel assembly based on molecular recognition

    PubMed Central

    Yamaguchi, Hiroyasu; Kobayashi, Yuichiro; Kobayashi, Ryosuke; Takashima, Yoshinori; Hashidzume, Akihito; Harada, Akira

    2012-01-01

    The formation of effective and precise linkages in bottom-up or top-down processes is important for the development of self-assembled materials. Self-assembly through molecular recognition events is a powerful tool for producing functionalized materials. Photoresponsive molecular recognition systems can permit the creation of photoregulated self-assembled macroscopic objects. Here we demonstrate that macroscopic gel assembly can be highly regulated through photoisomerization of an azobenzene moiety that interacts differently with two host molecules. A photoregulated gel assembly system is developed using polyacrylamide-based hydrogels functionalized with azobenzene (guest) or cyclodextrin (host) moieties. Reversible adhesion and dissociation of the host gel from the guest gel may be controlled by photoirradiation. The differential affinities of α-cyclodextrin or β-cyclodextrin for the trans-azobenzene and cis-azobenzene are employed in the construction of a photoswitchable gel assembly system. PMID:22215078

  3. Photoswitchable gel assembly based on molecular recognition.

    PubMed

    Yamaguchi, Hiroyasu; Kobayashi, Yuichiro; Kobayashi, Ryosuke; Takashima, Yoshinori; Hashidzume, Akihito; Harada, Akira

    2012-01-01

    The formation of effective and precise linkages in bottom-up or top-down processes is important for the development of self-assembled materials. Self-assembly through molecular recognition events is a powerful tool for producing functionalized materials. Photoresponsive molecular recognition systems can permit the creation of photoregulated self-assembled macroscopic objects. Here we demonstrate that macroscopic gel assembly can be highly regulated through photoisomerization of an azobenzene moiety that interacts differently with two host molecules. A photoregulated gel assembly system is developed using polyacrylamide-based hydrogels functionalized with azobenzene (guest) or cyclodextrin (host) moieties. Reversible adhesion and dissociation of the host gel from the guest gel may be controlled by photoirradiation. The differential affinities of α-cyclodextrin or β-cyclodextrin for the trans-azobenzene and cis-azobenzene are employed in the construction of a photoswitchable gel assembly system. PMID:22215078

  4. Organic-based molecular switches for molecular electronics.

    PubMed

    Fuentes, Noelia; Martín-Lasanta, Ana; Alvarez de Cienfuegos, Luis; Ribagorda, Maria; Parra, Andres; Cuerva, Juan M

    2011-10-01

    In a general sense, molecular electronics (ME) is the branch of nanotechnology which studies the application of molecular building blocks for the fabrication of electronic components. Among the different types of molecules, organic compounds have been revealed as promising candidates for ME, due to the easy access, great structural diversity and suitable electronic and mechanical properties. Thanks to these useful capabilities, organic molecules have been used to emulate electronic devices at the nanoscopic scale. In this feature article, we present the diverse strategies used to develop organic switches towards ME with special attention to non-volatile systems.

  5. Molecular cloning of protein-based polymers.

    PubMed

    Mi, Lixin

    2006-07-01

    Protein-based biopolymers have become a promising class of materials for both biomedical and pharmaceutical applications, as they have well-defined molecular weights, monomer compositions, as well as tunable chemical, biological, and mechanical properties. Using standard molecular biology tools, it is possible to design and construct genes encoding artificial proteins or protein-based polymers containing multiple repeats of amino acid sequences. This article reviews some of the traditional methods used for constructing DNA duplexes encoding these repeat-containing genes, including monomer generation, concatemerization, iterative oligomerization, and seamless cloning. A facile and versatile method, called modules of degenerate codons (MDC), which uses PCR and codon degeneracy to overcome some of the disadvantages of traditional methods, is introduced. Re-engineering of the random coil spacer domain of a bioactive protein, WPT2-3R, is used to demonstrate the utility of the MDC method. MDC re-constructed coding sequences facilitate further manipulations, such as insertion, deletion, and swapping of various sequence modules. A summary of some promising emerging techniques for synthesizing repetitive sequence-containing artificial proteins is also provided. PMID:16827576

  6. Molecular survey of hepatitis C virus in the touristic city of Mar del Plata, Argentina.

    PubMed

    Culasso, Andrés C A; Elizalde, Mercedes; Campos, Rodolfo H; Barbini, Luciana

    2012-01-01

    The global epidemiology of hepatitis C virus (HCV) may be roughly described by two groups of genotypes: the worldwide distributed ones (subtypes 1a, 1b, 2a and 3a, among others) and the endemic ones (subtypes 4a, 5a, 6a, among others). Epidemiological and population dynamic studies of the worldwide distributed genotypes have shown that subtypes 1a and 3a are common among intravenous drug users (IDUs) and that they are also in expansion in some countries. The molecular survey of HCV provides some clues about the epidemiological status of the infections in a local scale and the phylogenetic and demographic reconstruction analyses complement this study by inferring whether the infections of certain subtypes are in a steady state or expanding. Here, a molecular survey of the HCV variants that circulate in the touristic city of Mar del Plata (Buenos Aires, Argentina) was performed in samples obtained from 42 patients. The subtypes detected were 1a (32 patients), 3a (8 patients) and 1b (2 patients). The demographic history of subtype 1a inferred using the sequence data showed an exponential growth in the 1990's. The period of viral expansion was delayed compared with that observed for the same genotype in other countries where the transmission was associated with IDUs. Also, the phylogeographic analysis of HCV-1a showed a statistically significant association between the location of the samples and the phylogeny, which may be the result of the local transmission of HCV in the city. The molecular analysis helped in the description of the complex epidemiological context of a touristic city, and pointed out that some sanitary measures should be taken in order to reduce the transmission of HCV (and maybe of HIV) among IDUs. PMID:23028605

  7. Protein-based tumor molecular imaging probes

    PubMed Central

    Lin, Xin; Xie, Jin

    2013-01-01

    Molecular imaging is an emerging discipline which plays critical roles in diagnosis and therapeutics. It visualizes and quantifies markers that are aberrantly expressed during the disease origin and development. Protein molecules remain to be one major class of imaging probes, and the option has been widely diversified due to the recent advances in protein engineering techniques. Antibodies are part of the immunosystem which interact with target antigens with high specificity and affinity. They have long been investigated as imaging probes and were coupled with imaging motifs such as radioisotopes for that purpose. However, the relatively large size of antibodies leads to a half-life that is too long for common imaging purposes. Besides, it may also cause a poor tissue penetration rate and thus compromise some medical applications. It is under this context that various engineered protein probes, essentially antibody fragments, protein scaffolds, and natural ligands have been developed. Compared to intact antibodies, they possess more compact size, shorter clearance time, and better tumor penetration. One major challenge of using protein probes in molecular imaging is the affected biological activity resulted from random labeling. Site-specific modification, however, allows conjugation happening in a stoichiometric fashion with little perturbation of protein activity. The present review will discuss protein-based probes with focus on their application and related site-specific conjugation strategies in tumor imaging. PMID:20232092

  8. Density based visualization for molecular simulation.

    PubMed

    Rozmanov, Dmitri; Baoukina, Svetlana; Tieleman, D Peter

    2014-01-01

    Molecular visualization of structural information obtained from computer simulations is an important part of research work flow. A good visualization technique should be capable of eliminating redundant information and highlight important effects clarifying the key phenomena in the system. Current methods of presenting structural data are mostly limited to variants of the traditional ball-and-stick representation. This approach becomes less attractive when very large biological systems are simulated at microsecond timescales, and is less effective when coarse-grained models are used. Real time rendering of such large systems becomes a difficult task; the amount of information in one single frame of a simulation trajectory is enormous given the large number of particles; at the same time, each structure contains information about one configurational point of the system and no information about statistical weight of this specific configuration. In this paper we report a novel visualization technique based on spatial particle densities. The atomic densities are sampled on a high resolution 3-dimensional grid along a relatively short molecular dynamics trajectory using hundreds of configurations. The density information is then analyzed and visualized using the open-source ParaView software. The performance and capability of the method are demonstrated on two large systems simulated with the MARTINI coarse-grained force field: a lipid nanoparticle for delivering siRNA molecules and monolayers with a complex composition under conditions that induce monolayer collapse.

  9. Molecular characterization of Hb Hamilton Hill (HBA2: c.388delC), a novel HBA2 variant generating a premature termination codon and truncated HBA2 chain.

    PubMed

    Qadah, Talal; Finlayson, Jill; North, Emma; Ghassemifar, Reza

    2015-01-01

    In recent years, the identification of α-thalassemias caused by nondeletional mutations has increased significantly due to the advancement of sensitive molecular genetics tools. We report clinical and experimental data for a novel frameshift mutation caused by a single base deletion at position 388 in exon 3 of the α2-globin gene (HBA2: c.388delC; Hb Hamilton Hill), resulting in the phenotype of α-thalassemia (α-thal). Hb Hamilton Hill was identified in an adult female of unknown ethnicity investigated for unexplained microcytosis. Direct DNA sequencing of the HBA2 gene revealed a heterozygous mutation, HBA2: c.388delC, and the molecular effect of this mutation was assessed experimentally using our previously described in vitro model. The experimental analysis involved transfection of a human bladder carcinoma (5637) cell line with expression vectors carrying either HBA2-wild type (HBA2-WT) or HBA2: c.388delC followed by total RNA purification and cDNA synthesis. Both wild type and mutant gene expression was studied and compared at the transcriptional and translational levels using quantitative real time polymerase chain reaction (qReTi-PCR) and immunofluorochemistry (IFC), respectively. Our experimental data showed a significant reduction by 25.0% (p = 0.04) in the transcriptional activity generated from HBA2: c.388delC compared to HBA2-WT. As a result of this base deletion, a frameshift in the open reading frame generates a premature termination codon (PTC) at codon 132 of exon 3 resulting in the formation of a truncated α-globin chain. The truncated α-globin chain, observed by the IFC technique, is most likely unstable and undergoes a rapid turnover resulting in the thalassemic phenotype.

  10. Molecular and genetic bases of pancreatic cancer.

    PubMed

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

    2012-06-01

    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  11. Optical materials based on molecular nanoparticles.

    PubMed

    Patra, A; Chandaluri, Ch G; Radhakrishnan, T P

    2012-01-21

    A major part of contemporary nanomaterials research is focused on metal and semiconductor nanoparticles, constituted of extended lattices of atoms or ions. Molecular nanoparticles assembled from small molecules through non-covalent interactions are relatively less explored but equally fascinating materials. Their unique and versatile characteristics have attracted considerable attention in recent years, establishing their identity and status as a novel class of nanomaterials. Optical characteristics of molecular nanoparticles capture the essence of their nanoscale features and form the basis of a variety of applications. This review describes the advances made in the field of fabrication of molecular nanoparticles, the wide spectrum of their optical and nonlinear optical characteristics and explorations of the potential applications that exploit their unique optical attributes.

  12. Accurate Molecular Polarizabilities Based on Continuum Electrostatics

    PubMed Central

    Truchon, Jean-François; Nicholls, Anthony; Iftimie, Radu I.; Roux, Benoît; Bayly, Christopher I.

    2013-01-01

    A novel approach for representing the intramolecular polarizability as a continuum dielectric is introduced to account for molecular electronic polarization. It is shown, using a finite-difference solution to the Poisson equation, that the Electronic Polarization from Internal Continuum (EPIC) model yields accurate gas-phase molecular polarizability tensors for a test set of 98 challenging molecules composed of heteroaromatics, alkanes and diatomics. The electronic polarization originates from a high intramolecular dielectric that produces polarizabilities consistent with B3LYP/aug-cc-pVTZ and experimental values when surrounded by vacuum dielectric. In contrast to other approaches to model electronic polarization, this simple model avoids the polarizability catastrophe and accurately calculates molecular anisotropy with the use of very few fitted parameters and without resorting to auxiliary sites or anisotropic atomic centers. On average, the unsigned error in the average polarizability and anisotropy compared to B3LYP are 2% and 5%, respectively. The correlation between the polarizability components from B3LYP and this approach lead to a R2 of 0.990 and a slope of 0.999. Even the F2 anisotropy, shown to be a difficult case for existing polarizability models, can be reproduced within 2% error. In addition to providing new parameters for a rapid method directly applicable to the calculation of polarizabilities, this work extends the widely used Poisson equation to areas where accurate molecular polarizabilities matter. PMID:23646034

  13. Molecular Nanocapsules Based on Amphiphilic Hyperbranched Polyglycerols.

    PubMed

    Sunder; Krämer; Hanselmann; Mülhaupt; Frey

    1999-12-01

    Polar dyes can be solubilized in apolar media-molecular nanocapsules with hydrophilic interiors have been prepared (see schematic representation) using polyglycerols with narrow polydispersity and simple esterification with fatty acids. These unimolecular micelles offer attractive potential for a variety of applications ranging from controlled drug release to the design of microreactors and catalysts.

  14. Quantitative Molecular Thermochemistry Based on Path Integrals

    SciTech Connect

    Glaesemann, K R; Fried, L E

    2005-03-14

    The calculation of thermochemical data requires accurate molecular energies and heat capacities. Traditional methods rely upon the standard harmonic normal mode analysis to calculate the vibrational and rotational contributions. We utilize path integral Monte Carlo (PIMC) for going beyond the harmonic analysis, to calculate the vibrational and rotational contributions to ab initio energies. This is an application and extension of a method previously developed in our group.

  15. [Department of the molecular bases of semiotics].

    PubMed

    Ternovyĭ, K S

    1995-01-01

    Department of molecular basis of semiotics was organized in 1986. The main task of the department was to work out new approaches in estimation of the state of immune and blood system at the tissue, cell and molecular levels, using biochemical, biophysical and molecular biology techniques. There are several main directions of scientific investigations at the department. Most informational methods were collected in "immunological portrait" for differential diagnostic and complex investigation of the immune system of autoimmune patients. This group of techniques was used to study changes in the immune system of Kievites after the Chernobyl disaster. A decrease of complement and thymic serum activity was detected. Antibodies against nuclear components appeared in 20% of donors. And a higher of circulating immune complex of low molecular weight was observed. Low level of thymic serum activity in blood of autoimmune patients with rheumatoid arthritis, lupus erythematosus, diabetes, herpes and other depends on the appearance of zinc-independent timuline inhibitor less then 2000 D. Another kind of thymic hormone inhibitors was detected in thymectomized adult mice. Its effect disappears when zinc added in blood rather due to competition for lymphocyte surface receptors timuline and its inactive analogue than other mechanism. Therapeutic effect of UV irradiation of patients' blood was shown to be closely connected with the changes in thymic serum activity in respect to stabilization of thymic hormone/inhibitor ratio. The immunochemical techniques were used to detect and investigate tumor-associated chromatin antigens in human and animal tumor cells. Antigens not found in normal tissues were detected when using rabbit antibodies against chromatin of rat hepatocarcinoma and human colon and carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Molecular Bases of Cutaneous and Uveal Melanomas

    PubMed Central

    Gaudi, Sudeep; Messina, Jane L.

    2011-01-01

    Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK) pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin, melanoma most commonly affects the eye. Data for the constitutive activation of the MAPK pathway in uveal melanoma exists as well, however, not through mutations of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the following discussion, we review the major molecular pathways implicated in both familial and sporadic cutaneous melanomagenesis, the former accounting for approximately 10% of cases. Additionally, we discuss the molecular pathways for which preliminary evidence suggests a role in uveal melanomagenesis. PMID:21876842

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

    PubMed

    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

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

    PubMed

    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. Molecular bases of plant resistance to arthropods.

    PubMed

    Smith, C Michael; Clement, Stephen L

    2012-01-01

    Arthropod-resistant crops provide significant ecological and economic benefits to global agriculture. Incompatible interactions involving resistant plants and avirulent pest arthropods are mediated by constitutively produced and arthropod-induced plant proteins and defense allelochemicals synthesized by resistance gene products. Cloning and molecular mapping have identified the Mi-1.2 and Vat arthropod resistance genes as CC-NBS-LRR (coiled coil-nucleotide binding site-leucine rich repeat) subfamily NBS-LRR resistance proteins, as well as several resistance gene analogs. Genetic linkage mapping has identified more than 100 plant resistance gene loci and linked molecular markers used in cultivar development. Rice and sorghum arthropod-resistant cultivars and, to a lesser extent, raspberry and wheat cultivars are components of integrated pest management (IPM) programs in Asia, Australia, Europe, and North America. Nevertheless, arthropod resistance in most food and fiber crops has not been integrated due primarily to the application of synthetic insecticides. Plant and arthropod genomics provide many opportunities to more efficiently develop arthropod-resistant plants, but integration of resistant cultivars into IPM programs will succeed only through interdisciplinary collaboration.

  20. Molecular bases of plant resistance to arthropods.

    PubMed

    Smith, C Michael; Clement, Stephen L

    2012-01-01

    Arthropod-resistant crops provide significant ecological and economic benefits to global agriculture. Incompatible interactions involving resistant plants and avirulent pest arthropods are mediated by constitutively produced and arthropod-induced plant proteins and defense allelochemicals synthesized by resistance gene products. Cloning and molecular mapping have identified the Mi-1.2 and Vat arthropod resistance genes as CC-NBS-LRR (coiled coil-nucleotide binding site-leucine rich repeat) subfamily NBS-LRR resistance proteins, as well as several resistance gene analogs. Genetic linkage mapping has identified more than 100 plant resistance gene loci and linked molecular markers used in cultivar development. Rice and sorghum arthropod-resistant cultivars and, to a lesser extent, raspberry and wheat cultivars are components of integrated pest management (IPM) programs in Asia, Australia, Europe, and North America. Nevertheless, arthropod resistance in most food and fiber crops has not been integrated due primarily to the application of synthetic insecticides. Plant and arthropod genomics provide many opportunities to more efficiently develop arthropod-resistant plants, but integration of resistant cultivars into IPM programs will succeed only through interdisciplinary collaboration. PMID:21910639

  1. A dual input DNA-based molecular switch.

    PubMed

    Nesterova, Irina V; Elsiddieg, Siddieg O; Nesterov, Evgueni E

    2014-11-01

    We have designed and characterized a DNA-based molecular switch which processes two physiologically relevant inputs: pH (i.e. alkalinisation) and enzymatic activity, and generates a chemical output (in situ synthesized oligonucleotide). The design, based on allosteric interactions between i-motif and hairpin stem within the DNA molecule, addresses such critical physiological system parameters as molecular simplicity, tunability, orthogonality of the two input sensing domains, and compatibility with intracellular operation/delivery. PMID:25099914

  2. The cell as the smallest DNA-based molecular computer.

    PubMed

    Ji, S

    1999-10-01

    The pioneering work of Adleman (1994) demonstrated that DNA molecules in test tubes can be manipulated to perform a certain type of mathematical computation. This has stimulated a theoretical interest in the possibility of constructing DNA-based molecular computers. To gauge the practicality of realizing such microscopic computers, it was thought necessary to learn as much as possible from the biology of the living cell--presently the only known DNA-based molecular computer in existence. Here the recently developed theoretical model of the living cell (the Bhopalator) and its associated theories (e.g. cell language), principles, laws and concepts (e.g. conformons, IDS's) are briefly reviewed and summarized in the form of a set of five laws of 'molecular semiotics' (synonyms include 'microsemiotics', 'cellular semiotics', or 'cytosemiotics') the study of signs mediating measurement, computation, and communication on the cellular and molecular levels. Hopefully, these laws will find practical applications in designing DNA-based computing systems.

  3. Inquiry-Based Learning of Molecular Phylogenetics

    ERIC Educational Resources Information Center

    Campo, Daniel; Garcia-Vazquez, Eva

    2008-01-01

    Reconstructing phylogenies from nucleotide sequences is a challenge for students because it strongly depends on evolutionary models and computer tools that are frequently updated. We present here an inquiry-based course aimed at learning how to trace a phylogeny based on sequences existing in public databases. Computer tools are freely available…

  4. Visual-size molecular recognition based on gels.

    PubMed

    Tu, Tao; Fang, Weiwei; Sun, Zheming

    2013-10-01

    Since their discovery, stimuli-responsive organogels have garnered considerable and increasing attention from a broad range of research fields. In consideration of an one-dimensional ordered relay in anisotropic phase, the assembled gel networks can amplify various properties of the functional moieties possessed by the gelator molecules. Recently, substantial efforts have been focused on the development of facile, straightforward, and low-cost molecular recognition approaches by using nanostructured gel matrices as visual sensing platforms. In this research news, the recent progresses in macroscopic or visual-size molecular recognition for a number of homologues, isomers, and anions, as well as extremely challenging chiral enantiomers, using polymer and molecular gels are reviewed. Several strategies--including guest molecular competition, hydrogen-bonding blocking, and metal-coordination--for visual discrimination are included. Finally, the future trends and potential application in facile visual-size molecular recognition based on organogel matrices are highlighted. PMID:24089348

  5. Optimal separable bases and molecular collisions

    SciTech Connect

    Poirier, L W

    1997-12-01

    A new methodology is proposed for the efficient determination of Green`s functions and eigenstates for quantum systems of two or more dimensions. For a given Hamiltonian, the best possible separable approximation is obtained from the set of all Hilbert space operators. It is shown that this determination itself, as well as the solution of the resultant approximation, are problems of reduced dimensionality for most systems of physical interest. Moreover, the approximate eigenstates constitute the optimal separable basis, in the sense of self-consistent field theory. These distorted waves give rise to a Born series with optimized convergence properties. Analytical results are presented for an application of the method to the two-dimensional shifted harmonic oscillator system. The primary interest however, is quantum reactive scattering in molecular systems. For numerical calculations, the use of distorted waves corresponds to numerical preconditioning. The new methodology therefore gives rise to an optimized preconditioning scheme for the efficient calculation of reactive and inelastic scattering amplitudes, especially at intermediate energies. This scheme is particularly suited to discrete variable representations (DVR`s) and iterative sparse matrix methods commonly employed in such calculations. State to state and cumulative reactive scattering results obtained via the optimized preconditioner are presented for the two-dimensional collinear H + H{sub 2} {yields} H{sub 2} + H system. Computational time and memory requirements for this system are drastically reduced in comparison with other methods, and results are obtained for previously prohibitive energy regimes.

  6. Supramolecular polymers constructed by crown ether-based molecular recognition.

    PubMed

    Zheng, Bo; Wang, Feng; Dong, Shengyi; Huang, Feihe

    2012-03-01

    Supramolecular polymers, polymeric systems beyond the molecule, have attracted more and more attention from scientists due to their applications in various fields, including stimuli-responsive materials, healable materials, and drug delivery. Due to their good selectivity and convenient enviro-responsiveness, crown ether-based molecular recognition motifs have been actively employed to fabricate supramolecular polymers with interesting properties and novel applications in recent years. In this tutorial review, we classify supramolecular polymers based on their differences in topology and cover recent advances in the marriage between crown ether-based molecular recognition and polymer science.

  7. Electronic transport properties of a quinone-based molecular switch

    NASA Astrophysics Data System (ADS)

    Zheng, Ya-Peng; Bian, Bao-An; Yuan, Pei-Pei

    2016-09-01

    In this paper, we carried out first-principles calculations based on density functional theory and non-equilibrium Green's function to investigate the electronic transport properties of a quinone-based molecule sandwiched between two Au electrodes. The molecular switch can be reversibly switched between the reduced hydroquinone (HQ) and oxidized quinone (Q) states via redox reactions. The switching behavior of two forms is analyzed through their I- V curves, transmission spectra and molecular projected self-consistent Hamiltonian at zero bias. Then we discuss the transmission spectra of the HQ and Q forms at different bias, and explain the oscillation of current according to the transmission eigenstates of LUMO energy level for Q form. The results suggest that this kind of a quinone-based molecule is usable as one of the good candidates for redox-controlled molecular switches.

  8. Artificial nanomachines based on interlocked molecular species: recent advances.

    PubMed

    Balzani, Vincenzo; Credi, Alberto; Silvi, Serena; Venturi, Margherita

    2006-11-01

    The bottom-up construction and operation of nanoscale machines and motors, that is, supramolecular systems wherein the molecular components can be set in motion in a controlled manner for ultimately accomplishing a function, is a topic of great interest in nanoscience and a fascinating challenge of nanotechnology. The field of artificial molecular machines and motors is growing at an astonishing rate and is attracting a great deal of interest. Research in the last decade has shown that species made of interlocked molecular components like rotaxanes, catenanes and related systems are most attractive candidates. In recent times, the evolution of the structural and functional design of such systems has led to the construction and operation of complex molecular machines that, in some cases, are able to do specific tasks. This tutorial review is intended to discuss the design principles for nanomachines based on interlocked molecules, and to provide a timely overview on representative prototype systems.

  9. Molecular partitioning based on the kinetic energy density

    NASA Astrophysics Data System (ADS)

    Noorizadeh, Siamak

    2016-05-01

    Molecular partitioning based on the kinetic energy density is performed to a number of chemical species, which show non-nuclear attractors (NNA) in their gradient maps of the electron density. It is found that NNAs are removed using this molecular partitioning and although the virial theorem is not valid for all of the basins obtained in the being used AIM, all of the atoms obtained using the new approach obey this theorem. A comparison is also made between some atomic topological parameters which are obtained from the new partitioning approach and those calculated based on the electron density partitioning.

  10. Plasmonic-Based Electrochemical Impedance Spectroscopy: Application to Molecular Binding

    PubMed Central

    Lu, Jin; Wang, Wei; Wang, Shaopeng; Shan, Xiaonan; Li, Jinghong; Tao, Nongjian

    2012-01-01

    Plasmonic-based electrochemical impedance spectroscopy (P-EIS) is developed to investigate molecular binding on surfaces. Its basic principle relies on the sensitive dependence of surface plasmon resonance (SPR) signal on surface charge density, which is modulated by applying an AC potential to a SPR chip surface. The AC component of the SPR response gives the electrochemical impedance, and the DC component provides the conventional SPR detection. The plasmonic-based impedance measured over a range of frequency is in quantitative agreement with the conventional electrochemical impedance. Compared to the conventional SPR detection, P-EIS is sensitive to molecular binding taking place on the chip surface, and less sensitive to bulk refractive index changes or non-specific binding. Moreover, this new approach allows for simultaneous SPR and surface impedance analysis of molecular binding processes. PMID:22122514

  11. Inorganic nanoparticle-based contrast agents for molecular imaging

    PubMed Central

    Cho, Eun Chul; Glaus, Charles; Chen, Jingyi; Welch, Michael J.; Xia, Younan

    2010-01-01

    Inorganic nanoparticles including semiconductor quantum dots, iron oxide nanoparticles, and gold nanoparticles have been developed as contrast agents for diagnostics by molecular imaging. Compared to traditional contrast agents, nanoparticles offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size, and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multi-modal imaging. Here, we review recent advances in the development of contrast agents based on inorganic nanoparticles for molecular imaging, with a touch on contrast enhancement, surface modification, tissue targeting, clearance, and toxicity. As research efforts intensify, contrast agents based on inorganic nanoparticles that are highly sensitive, target-specific, and safe to use are expected to enter clinical applications in the near future. PMID:21074494

  12. Efficient Molecular Dynamics Simulations of Multiple Radical Center Systems Based on the Fragment Molecular Orbital Method

    SciTech Connect

    Nakata, Hiroya; Schmidt, Michael W; Fedorov, Dmitri G; Kitaura, Kazuo; Nakamura, Shinichiro; Gordon, Mark S

    2014-10-16

    The fully analytic energy gradient has been developed and implemented for the restricted open-shell Hartree–Fock (ROHF) method based on the fragment molecular orbital (FMO) theory for systems that have multiple open-shell molecules. The accuracy of the analytic ROHF energy gradient is compared with the corresponding numerical gradient, illustrating the accuracy of the analytic gradient. The ROHF analytic gradient is used to perform molecular dynamics simulations of an unusual open-shell system, liquid oxygen, and mixtures of oxygen and nitrogen. These molecular dynamics simulations provide some insight about how triplet oxygen molecules interact with each other. Timings reveal that the method can calculate the energy gradient for a system containing 4000 atoms in only 6 h. Therefore, it is concluded that the FMO-ROHF method will be useful for investigating systems with multiple open shells.

  13. Efficient molecular dynamics simulations of multiple radical center systems based on the fragment molecular orbital method.

    PubMed

    Nakata, Hiroya; Schmidt, Michael W; Fedorov, Dmitri G; Kitaura, Kazuo; Nakamura, Shinichiro; Gordon, Mark S

    2014-10-16

    The fully analytic energy gradient has been developed and implemented for the restricted open-shell Hartree-Fock (ROHF) method based on the fragment molecular orbital (FMO) theory for systems that have multiple open-shell molecules. The accuracy of the analytic ROHF energy gradient is compared with the corresponding numerical gradient, illustrating the accuracy of the analytic gradient. The ROHF analytic gradient is used to perform molecular dynamics simulations of an unusual open-shell system, liquid oxygen, and mixtures of oxygen and nitrogen. These molecular dynamics simulations provide some insight about how triplet oxygen molecules interact with each other. Timings reveal that the method can calculate the energy gradient for a system containing 4000 atoms in only 6 h. Therefore, it is concluded that the FMO-ROHF method will be useful for investigating systems with multiple open shells.

  14. [Study on material base of Ligusticum wallichii for treating brain ischemia and its molecular mechanism based on molecular docking].

    PubMed

    Song, Xiang-gang; Zhou, Wei; Chen, Chao; Wang, Shu-mei; Liang, Sheng-wang

    2015-06-01

    To explore the effective ingredients and mechanism of Ligusticum wallichii in treating brain ischemia. Four brain ischemia-related target proteins were selected in the joint screening for the 45 component in L. wallichii reported in literatures based on molecular docking by reference to the corresponding drugs in the market. According to the docking results, multiple components in L. wallichii, such as phthalides, were superior to the corresponding drugs in the market, suggesting that they may be the major effective components in L. wallichii for treating brain ischemia. The method can be used to study the material base and molecular mechanism of traditional Chinese medicines.

  15. Computer-Based Semantic Network in Molecular Biology: A Demonstration.

    ERIC Educational Resources Information Center

    Callman, Joshua L.; And Others

    This paper analyzes the hardware and software features that would be desirable in a computer-based semantic network system for representing biology knowledge. It then describes in detail a prototype network of molecular biology knowledge that has been developed using Filevision software and a Macintosh computer. The prototype contains about 100…

  16. Intermolecular G-quadruplex-based universal quencher free molecular beacon.

    PubMed

    Zhou, Hui; Xie, Su-Jin; Li, Ji-Shan; Wu, Zai-Sheng; Shen, Guo-Li

    2012-11-11

    A simple and universal quencher-free molecular beacon (MB) with low background fluorescence is developed based on an intermolecular G-quadruplex signaling probe. Unlike previous fluorescent MB strategies, it can function without any fluorophore and quencher modifications on its hairpin sequence.

  17. Molecular Recognition: Detection of Colorless Compounds Based on Color Change

    ERIC Educational Resources Information Center

    Khalafi, Lida; Kashani, Samira; Karimi, Javad

    2016-01-01

    A laboratory experiment is described in which students measure the amount of cetirizine in allergy-treatment tablets based on molecular recognition. The basis of recognition is competition of cetirizine with phenolphthalein to form an inclusion complex with ß-cyclodextrin. Phenolphthalein is pinkish under basic condition, whereas it's complex form…

  18. Intelligent DNA-based molecular diagnostics using linked genetic markers

    SciTech Connect

    Pathak, D.K.; Perlin, M.W.; Hoffman, E.P.

    1994-12-31

    This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system`s successful diagnosis of DMD carrier and affected individuals from raw clinical data.

  19. [Morphofunctional and molecular bases of pineal gland aging].

    PubMed

    Khavinson, V Kh; Lin'kova, N S

    2012-01-01

    The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

  20. Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

    NASA Astrophysics Data System (ADS)

    Sato, Yukari; Natsume, Ryo; Prokop, Zbynek; Brezovsky, Jan; Chaloupkova, Radka; Damborsky, Jiri; Nagata, Yuji; Senda, Toshiya

    Enzymes are widely used for the synthesis of pharmaceuticals, agrochemicals, and food additives because they can catalyze high enantioselective transformations. In order to construct selective enzymes by protein engineering, it is important to understand the molecular basis of enzyme-substrate interactions that contribute to enantioselectivity. The haloalkane dehalogenase DbjA showed high enantioselectivity for two racemic mixtures: α-bromoesters and β-bromoalkanes. Thermodynamic analysis, protein crystallography, and computer simulations indicated that DbjA carries two bases for the enantiodiscrimination of each racemic mixture. This study helps us understand the molecular basis of the enantioselectivity and opens up new possibilities for constructing enantiospecific biocatalysts through protein engineering.

  1. Theory of zwitterionic molecular-based organic magnets

    NASA Astrophysics Data System (ADS)

    Shelton, William A.; Aprà, Edoardo; Sumpter, Bobby G.; Saraiva-Souza, Aldilene; Souza Filho, Antonio G.; Nero, Jordan Del; Meunier, Vincent

    2011-08-01

    We describe a class of organic molecular magnets based on zwitterionic molecules (betaine derivatives) possessing donor, π bridge, and acceptor groups. Using extensive electronic structure calculations we show the electronic ground-state in these systems is magnetic. In addition, we show that the large energy differences computed for the various magnetic states indicate a high Neel temperature. The quantum mechanical nature of the magnetic properties originates from the conjugated π bridge (only p electrons) in cooperation with the molecular donor-acceptor character. The exchange interactions between electron spin are strong, local, and independent on the length of the π bridge.

  2. Molecular rectifiers: a new design based on asymmetric anchoring moieties.

    PubMed

    Van Dyck, Colin; Ratner, Mark A

    2015-03-11

    The quest for a molecular rectifier is among the major challenges of molecular electronics. We introduce three simple rules to design an efficient rectifying molecule and demonstrate its functioning at the theoretical level, relying on the NEGF-DFT technique. The design rules notably require both the introduction of asymmetric anchoring moieties and a decoupling bridge. They lead to a new rectification mechanism based on the compression and control of the HOMO/LUMO gap by the electrode Fermi levels, arising from a pinning effect. Significant rectification ratios up to 2 orders of magnitude are theoretically predicted as the mechanism opposes resonant to nonresonant tunneling. PMID:25706442

  3. Gesture Interaction Browser-Based 3D Molecular Viewer.

    PubMed

    Virag, Ioan; Stoicu-Tivadar, Lăcrămioara; Crişan-Vida, Mihaela

    2016-01-01

    The paper presents an open source system that allows the user to interact with a 3D molecular viewer using associated hand gestures for rotating, scaling and panning the rendered model. The novelty of this approach is that the entire application is browser-based and doesn't require installation of third party plug-ins or additional software components in order to visualize the supported chemical file formats. This kind of solution is suitable for instruction of users in less IT oriented environments, like medicine or chemistry. For rendering various molecular geometries our team used GLmol (a molecular viewer written in JavaScript). The interaction with the 3D models is made with Leap Motion controller that allows real-time tracking of the user's hand gestures. The first results confirmed that the resulting application leads to a better way of understanding various types of translational bioinformatics related problems in both biomedical research and education. PMID:27350455

  4. Multiferroic materials based on organic transition-metal molecular nanowires.

    PubMed

    Wu, Menghao; Burton, J D; Tsymbal, Evgeny Y; Zeng, Xiao Cheng; Jena, Puru

    2012-09-01

    We report on the density functional theory aided design of a variety of organic ferroelectric and multiferroic materials by functionalizing crystallized transition-metal molecular sandwich nanowires with chemical groups such as -F, -Cl, -CN, -NO(2), ═O, and -OH. Such functionalized polar wires exhibit molecular reorientation in response to an electric field. Ferroelectric polarizations as large as 23.0 μC/cm(2) are predicted in crystals based on fully hydroxylized sandwich nanowires. Furthermore, we find that organic nanowires formed by sandwiching transition-metal atoms in croconic and rhodizonic acids, dihydroxybenzoquinone, dichloro-dihydroxy-p-benzoquinone, or benzene decorated by -COOH groups exhibit ordered magnetic moments, leading to a multiferroic organometallic crystal. When crystallized through hydrogen bonds, the microscopic molecular reorientation translates into a switchable polarization through proton transfer. A giant interface magnetoelectric response that is orders of magnitude greater than previously reported for conventional oxide heterostructure interfaces is predicted. PMID:22881120

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

    PubMed

    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.

  6. An OR logic gate based on two molecular beacons.

    PubMed

    Guo, Jing; Yang, Renqiang

    2012-03-01

    Design of elementary molecular logic gates is the key and the fundamental of performing complicated Boolean calculations. Herein, we report a strategy for constructing a DNA-based OR gate by using the mechanism of sequence recognition and the principle of fluorescence resonance energy transfer (FRET). In this system, the gate is entirely composed of a single strand of DNA (A, B and C) and the inputs are the molecular beacon probes (MB1 and MB2). Changes in fluorescence intensity confirm the realization of the OR logic operation and electrophoresis experiments verify these results. Our successful application of DNA to perform the binary operation represents that DNA can serve as an efficient biomaterial for designing molecular logic gates and devices.

  7. Gesture Interaction Browser-Based 3D Molecular Viewer.

    PubMed

    Virag, Ioan; Stoicu-Tivadar, Lăcrămioara; Crişan-Vida, Mihaela

    2016-01-01

    The paper presents an open source system that allows the user to interact with a 3D molecular viewer using associated hand gestures for rotating, scaling and panning the rendered model. The novelty of this approach is that the entire application is browser-based and doesn't require installation of third party plug-ins or additional software components in order to visualize the supported chemical file formats. This kind of solution is suitable for instruction of users in less IT oriented environments, like medicine or chemistry. For rendering various molecular geometries our team used GLmol (a molecular viewer written in JavaScript). The interaction with the 3D models is made with Leap Motion controller that allows real-time tracking of the user's hand gestures. The first results confirmed that the resulting application leads to a better way of understanding various types of translational bioinformatics related problems in both biomedical research and education.

  8. Emerging technologies in extracellular vesicle-based molecular diagnostics.

    PubMed

    Jia, Shidong; Zocco, Davide; Samuels, Michael L; Chou, Michael F; Chammas, Roger; Skog, Johan; Zarovni, Natasa; Momen-Heravi, Fatemeh; Kuo, Winston Patrick

    2014-04-01

    Extracellular vesicles (EVs), including exosomes and microvesicles, have been shown to carry a variety of biomacromolecules including mRNA, microRNA and other non-coding RNAs. Within the past 5 years, EVs have emerged as a promising minimally invasive novel source of material for molecular diagnostics. Although EVs can be easily identified and collected from biological fluids, further research and proper validation is needed in order for them to be useful in the clinical setting. In addition, innovative and more efficient means of nucleic acid profiling are needed to facilitate investigations into the cellular and molecular mechanisms of EV function and to establish their potential as useful clinical biomarkers and therapeutic tools. In this article, we provide an overview of recent technological improvements in both upstream EV isolation and downstream analytical technologies, including digital PCR and next generation sequencing, highlighting future prospects for EV-based molecular diagnostics.

  9. Optically induced transport through semiconductor-based molecular electronics

    SciTech Connect

    Li, Guangqi; Seideman, Tamar; Fainberg, Boris D.

    2015-04-21

    A tight binding model is used to investigate photoinduced tunneling current through a molecular bridge coupled to two semiconductor electrodes. A quantum master equation is developed within a non-Markovian theory based on second-order perturbation theory with respect to the molecule-semiconductor electrode coupling. The spectral functions are generated using a one dimensional alternating bond model, and the coupling between the molecule and the electrodes is expressed through a corresponding correlation function. Since the molecular bridge orbitals are inside the bandgap between the conduction and valence bands, charge carrier tunneling is inhibited in the dark. Subject to the dipole interaction with the laser field, virtual molecular states are generated via the absorption and emission of photons, and new tunneling channels open. Interesting phenomena arising from memory are noted. Such a phenomenon could serve as a switch.

  10. Genetic analysis and molecular characterization of Chinese sesame (Sesamum indicum L.) cultivars using Insertion-Deletion (InDel) and Simple Sequence Repeat (SSR) markers

    PubMed Central

    2014-01-01

    Background Sesame is an important and ancient oil crop in tropical and subtropical areas. China is one of the most important sesame producing countries with many germplasm accessions and excellent cultivars. Domestication and modern plant breeding have presumably narrowed the genetic basis of cultivated sesame. Several modern sesame cultivars were bred with a limited number of landrace cultivars in their pedigree. The genetic variation was subsequently reduced by genetic drift and selection. Characterization of genetic diversity of these cultivars by molecular markers is of great value to assist parental line selection and breeding strategy design. Results Three hundred and forty nine simple sequence repeat (SSR) and 79 insertion-deletion (InDel) markers were developed from cDNA library and reduced-representation sequencing of a sesame cultivar Zhongzhi 14, respectively. Combined with previously published SSR markers, 88 polymorphic markers were used to assess the genetic diversity, phylogenetic relationships, population structure, and allele distribution among 130 Chinese sesame accessions including 82 cultivars, 44 landraces and 4 wild germplasm accessions. A total of 325 alleles were detected, with the average gene diversity of 0.432. Model-based structure analysis revealed the presence of five subgroups belonging to two main groups, which were consistent with the results from principal coordinate analysis (PCA), phylogenetic clustering and analysis of molecular variance (AMOVA). Several missing or unique alleles were identified from particular types, subgroups or families, even though they share one or both parental/progenitor lines. Conclusions This report presented a by far most comprehensive characterization of the molecular and genetic diversity of sesame cultivars in China. InDels are more polymorphic than SSRs, but their ability for deciphering genetic diversity compared to the later. Improved sesame cultivars have narrower genetic basis than landraces

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

    NASA Astrophysics Data System (ADS)

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

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

  12. [Molecular bases of α-thalassemia in Argentina].

    PubMed

    Scheps, Karen G; Francipane, Liliana; Nash, Abigail; Cerrone, Gloria E; Copelli, Silvia B; Varela, Viviana

    2015-01-01

    The α-thalassemia is one of the most common hereditary disorders worldwide. Currently, molecular diagnostics is the only available tool to achieve an accurate diagnosis. The purpose of this study was to characterize the molecular bases of these syndromes in our environment and to establish genotype-phenotype associations. Through a combination of different molecular techniques and fluorescent in situ hybridization (FISH),we were able to find α-thalassemic mutations in 145 of the 184 patients (78.8%) studied with hematological parameters compatible with α-thalassemia. Deletions of the α-globin genes resulted the major molecular cause of the disease, and the most frequent mutation was -α(3.7), found in homozygous and heterozygous genotypes. In patients with α° phenotypes, other prevalent mutations were( _MED) and (_CAL/CAMP). The description of a sub-telomeric deletion in a patient with α-thalassemia and mental retardation was also achieved. β-thalassemic mutations in heterozygous state were found in 7.6% of the patients, who presented α-thalassemic clinical features (microcytosis and Hb A₂levels below 3.5%). Hematologic profiles for the α+ and α° genotypes were established for adult and pediatric patients. Hopefully, this work will provide guidelines for the detection of possible α-thalassemic carriers. It also highlights the collaborative work of hematologists, the biochemical and molecular biology laboratory and genetists, in order to provide appropriate genetic counseling.

  13. Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

    PubMed Central

    Algieri, Catia; Drioli, Enrico; Guzzo, Laura; Donato, Laura

    2014-01-01

    An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template) was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported. PMID:25196110

  14. [Molecular bases of α-thalassemia in Argentina].

    PubMed

    Scheps, Karen G; Francipane, Liliana; Nash, Abigail; Cerrone, Gloria E; Copelli, Silvia B; Varela, Viviana

    2015-01-01

    The α-thalassemia is one of the most common hereditary disorders worldwide. Currently, molecular diagnostics is the only available tool to achieve an accurate diagnosis. The purpose of this study was to characterize the molecular bases of these syndromes in our environment and to establish genotype-phenotype associations. Through a combination of different molecular techniques and fluorescent in situ hybridization (FISH),we were able to find α-thalassemic mutations in 145 of the 184 patients (78.8%) studied with hematological parameters compatible with α-thalassemia. Deletions of the α-globin genes resulted the major molecular cause of the disease, and the most frequent mutation was -α(3.7), found in homozygous and heterozygous genotypes. In patients with α° phenotypes, other prevalent mutations were( _MED) and (_CAL/CAMP). The description of a sub-telomeric deletion in a patient with α-thalassemia and mental retardation was also achieved. β-thalassemic mutations in heterozygous state were found in 7.6% of the patients, who presented α-thalassemic clinical features (microcytosis and Hb A₂levels below 3.5%). Hematologic profiles for the α+ and α° genotypes were established for adult and pediatric patients. Hopefully, this work will provide guidelines for the detection of possible α-thalassemic carriers. It also highlights the collaborative work of hematologists, the biochemical and molecular biology laboratory and genetists, in order to provide appropriate genetic counseling. PMID:25919868

  15. Bio-mimetic sensors based on molecularly imprinted membranes.

    PubMed

    Algieri, Catia; Drioli, Enrico; Guzzo, Laura; Donato, Laura

    2014-07-30

    An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template) was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported.

  16. Molecular imaging of cell-based cancer immunotherapy

    PubMed Central

    Liu, Gang; Swierczewska, Magdalena; Zhang, Xiaoming

    2011-01-01

    Cell-based cancer immunotherapy represents a new and powerful weapon in the arsenal of anticancer treatments. Non-invasive monitoring of the disposition, migration and destination of therapeutic cells will facilitate the development of cell based therapy. The therapeutic cells can be modified intrinsically by a reporter gene or labeled extrinsically by introducing imaging probes into the cells or on the cell surface before transplant. Various advanced non-invasive molecular imaging techniques are playing important roles in optimizing cellular therapy by tracking cells and monitoring the therapeutic effects of transplanted cells in vivo. This review will summarize the application of multiple molecular imaging modalities in cell-based cancer immunotherapy. PMID:21308113

  17. Molecular defects in the factor X gene caused by novel heterozygous mutations IVS5+1G>A and Asp409del.

    PubMed

    Zhou, J W; Liang, Q; Chen, Q; Xie, Y; Ding, Q L; Wang, X F; Xi, X D; Wang, H L

    2013-01-01

    Factor X (FX) deficiency is a rare autosomal-recessive bleeding disorder caused by diverse mutations in the F10 gene. To investigate the molecular basis of severe FX deficiency in a mildly hemorrhagic patient, variants of the F10 gene were detected by sequencing. A missense mutation was analysed by in vitro expression and modelling analysis, and a splice mutation using ectopic transcript analysis. The levels of activity of FX (FX:C) were <1% in both intrinsic and extrinsic pathway assays and 1.71% in chromogenic assay, the level of FX antigen (FX:Ag) was 53.36% in the proband. Two novel heterozygous mutations (IVS5+1G>A and Asp409del) were identified in the F10 gene. Ectopic transcript expression combined with informative marker (heterozygous Asp409del) analysis of the splice mutation (IVS5+1G>A) revealed and confirmed that the transcript from the mutated allele was absent, likely caused by the nonsense-mediated mRNA decay pathway. In vitro expression analysis showed that the Asp409del mutant led to a loss of enzymatic activity rather than impaired expression. Molecular modelling analysis confirmed that the Asp409del mutant dramatically altered the conformation of the 185-189 loop and impaired binding of the loop to sodium ions (Na(+) ), diminishing the enzymatic activity of FXa. This is the first report to clarify the molecular mechanisms of two naturally occurring F10 gene variants that cause severe FX deficiency.

  18. Optimizing legacy molecular dynamics software with directive-based offload

    NASA Astrophysics Data System (ADS)

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

    2015-10-01

    Directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In this paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also result in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMPS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel® Xeon Phi™ coprocessors and NVIDIA GPUs. The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS.

  19. Arthropod phylogeny based on eight molecular loci and morphology

    NASA Technical Reports Server (NTRS)

    Giribet, G.; Edgecombe, G. D.; Wheeler, W. C.

    2001-01-01

    The interrelationships of major clades within the Arthropoda remain one of the most contentious issues in systematics, which has traditionally been the domain of morphologists. A growing body of DNA sequences and other types of molecular data has revitalized study of arthropod phylogeny and has inspired new considerations of character evolution. Novel hypotheses such as a crustacean-hexapod affinity were based on analyses of single or few genes and limited taxon sampling, but have received recent support from mitochondrial gene order, and eye and brain ultrastructure and neurogenesis. Here we assess relationships within Arthropoda based on a synthesis of all well sampled molecular loci together with a comprehensive data set of morphological, developmental, ultrastructural and gene-order characters. The molecular data include sequences of three nuclear ribosomal genes, three nuclear protein-coding genes, and two mitochondrial genes (one protein coding, one ribosomal). We devised new optimization procedures and constructed a parallel computer cluster with 256 central processing units to analyse molecular data on a scale not previously possible. The optimal 'total evidence' cladogram supports the crustacean-hexapod clade, recognizes pycnogonids as sister to other euarthropods, and indicates monophyly of Myriapoda and Mandibulata.

  20. Graph-based interpretation of the molecular interstellar medium segmentation

    NASA Astrophysics Data System (ADS)

    Colombo, D.; Rosolowsky, E.; Ginsburg, A.; Duarte-Cabral, A.; Hughes, A.

    2015-12-01

    We present a generalization of the giant molecular cloud identification problem based on cluster analysis. The method we designed, SCIMES (Spectral Clustering for Interstellar Molecular Emission Segmentation) considers the dendrogram of emission in the broader framework of graph theory and utilizes spectral clustering to find discrete regions with similar emission properties. For Galactic molecular cloud structures, we show that the characteristic volume and/or integrated CO luminosity are useful criteria to define the clustering, yielding emission structures that closely reproduce `by-eye' identification results. SCIMES performs best on well-resolved, high-resolution data, making it complementary to other available algorithms. Using 12CO(1-0) data for the Orion-Monoceros complex, we demonstrate that SCIMES provides robust results against changes of the dendrogram-construction parameters, noise realizations and degraded resolution. By comparing SCIMES with other cloud decomposition approaches, we show that our method is able to identify all canonical clouds of the Orion-Monoceros region, avoiding the overdivision within high-resolution survey data that represents a common limitation of several decomposition algorithms. The Orion-Monoceros objects exhibit hierarchies and size-line width relationships typical to the turbulent gas in molecular clouds, although `the Scissors' region deviates from this common description. SCIMES represents a significant step forward in moving away from pixel-based cloud segmentation towards a more physical-oriented approach, where virtually all properties of the ISM can be used for the segmentation of discrete objects.

  1. Optimizing legacy molecular dynamics software with directive-based offload

    SciTech Connect

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

    2015-05-14

    The directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In our paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We also demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also result in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMAS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel (R) Xeon Phi (TM) coprocessors and NVIDIA GPUs: The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS. (C) 2015 Elsevier B.V. All rights reserved.

  2. Optimizing legacy molecular dynamics software with directive-based offload

    DOE PAGESBeta

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

    2015-05-14

    The directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In our paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We also demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also resultmore » in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMAS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel (R) Xeon Phi (TM) coprocessors and NVIDIA GPUs: The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS. (C) 2015 Elsevier B.V. All rights reserved.« less

  3. Predictive value of molecular drug resistance testing of Mycobacterium tuberculosis isolates in Valle del Cauca, Colombia.

    PubMed

    Ferro, Beatriz E; García, Pamela K; Nieto, Luisa Maria; van Soolingen, Dick

    2013-07-01

    Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first- and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in Mycobacterium tuberculosis, and especially in South America, there is a paucity of information regarding the frequencies and types of mutations associated with resistance to first- and second-line antituberculosis drugs. We therefore evaluated the performance of the GenoType kits in this region by testing 228 M. tuberculosis isolates in Colombia, including 134 resistant and 94 pansusceptible strains. Overall, the sensitivity and specificity of the GenoType MTBDRplus test ranged from 92 to 96% and 97 to 100%, respectively; the agreement index was optimal (Cohen's kappa, >0.8). The sensitivity of the GenoType MTBDRsl test ranged from 84 to 100% and the specificity from 88 to 100%. The most common mutations were katG S315T1, rpoB S531L, embB M306V, gyrA D94G, and rrs A1401G. Our results reflect the utility of the GenoType tests in Colombia; however, as some discordance still exists between the conventional and molecular approaches in resistance testing, we adhere to the recommendation that the GenoType tests serve as early guides for therapy, followed by phenotypic drug susceptibility testing for all cases.

  4. Estudio multifrecuencia del flujo bipolar-molecular asociado con la proto-estrella VLA 1623

    NASA Astrophysics Data System (ADS)

    Artur de la Villarmois, E.; Merlo, D. C.; Gómez, M.

    In this work; we present a multi-wavelength study of the bipolar molecular outflow associated with the VLA 1623 proto-star (age 10 yrs). We analyze images obtained by Spitzer as well as other images from the literature. We identify 32 H (2.12 m) emission knots and 25 objects predominantly emitting in the [4.5] m band; usually known as EGOs (Extended Green Objects). Seven of these emissions are new EGO candidates; five of which have 2.12 m counter-parts. We compare the morphology of the emissions at 2.12 m and [4.5] m with the bipolar molecular outflow; finding an excellent agreement. The emissions are quasi-regularly spaced. We determine a dynamical time of 194.3 yrs between consecutive knots; which agrees with the lapse of time between eruptive FU Orionis events. This suggests that events of this type experimented by the central source might be the cause of the intermittency in the detected emissions. FULL TEXT IN SPANISH

  5. Predictive Value of Molecular Drug Resistance Testing of Mycobacterium tuberculosis Isolates in Valle del Cauca, Colombia

    PubMed Central

    García, Pamela K.; Nieto, Luisa Maria; van Soolingen, Dick

    2013-01-01

    Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first- and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in Mycobacterium tuberculosis, and especially in South America, there is a paucity of information regarding the frequencies and types of mutations associated with resistance to first- and second-line antituberculosis drugs. We therefore evaluated the performance of the GenoType kits in this region by testing 228 M. tuberculosis isolates in Colombia, including 134 resistant and 94 pansusceptible strains. Overall, the sensitivity and specificity of the GenoType MTBDRplus test ranged from 92 to 96% and 97 to 100%, respectively; the agreement index was optimal (Cohen's kappa, >0.8). The sensitivity of the GenoType MTBDRsl test ranged from 84 to 100% and the specificity from 88 to 100%. The most common mutations were katG S315T1, rpoB S531L, embB M306V, gyrA D94G, and rrs A1401G. Our results reflect the utility of the GenoType tests in Colombia; however, as some discordance still exists between the conventional and molecular approaches in resistance testing, we adhere to the recommendation that the GenoType tests serve as early guides for therapy, followed by phenotypic drug susceptibility testing for all cases. PMID:23658272

  6. [Evolution and systematics of nematodes based on molecular investigation].

    PubMed

    Okulewicz, Anna; Perec, Agnieszka

    2004-01-01

    Evolution and systematics of nematodes based on molecular investigation. The use of molecular phylogenetics to examine the interrelationships between animal parasites, free-living nematodes, and plant parasites versus traditional classification based on morphological-ecological characters was discussed and reviewed. Distinct differences were observed between parasitic nematodes and free-living ones. Within the former group, animal parasites turned out to be distinctly different from plant parasites. Using small subunit of ribosomal RNA gene sequence from a wide range of nematodes, there is a possibility to compare animal-parasitic, plant-parasitic and free-living taxa. Nowadays the parasitic nematodes expressed sequence tag (EST) project is currently generating sequence information to provide a new source of data to examine the evolutionary history of this taxonomic group. PMID:16859012

  7. Context-based preprocessing of molecular docking data

    PubMed Central

    2013-01-01

    Background Data preprocessing is a major step in data mining. In data preprocessing, several known techniques can be applied, or new ones developed, to improve data quality such that the mining results become more accurate and intelligible. Bioinformatics is one area with a high demand for generation of comprehensive models from large datasets. In this article, we propose a context-based data preprocessing approach to mine data from molecular docking simulation results. The test cases used a fully-flexible receptor (FFR) model of Mycobacterium tuberculosis InhA enzyme (FFR_InhA) and four different ligands. Results We generated an initial set of attributes as well as their respective instances. To improve this initial set, we applied two selection strategies. The first was based on our context-based approach while the second used the CFS (Correlation-based Feature Selection) machine learning algorithm. Additionally, we produced an extra dataset containing features selected by combining our context strategy and the CFS algorithm. To demonstrate the effectiveness of the proposed method, we evaluated its performance based on various predictive (RMSE, MAE, Correlation, and Nodes) and context (Precision, Recall and FScore) measures. Conclusions Statistical analysis of the results shows that the proposed context-based data preprocessing approach significantly improves predictive and context measures and outperforms the CFS algorithm. Context-based data preprocessing improves mining results by producing superior interpretable models, which makes it well-suited for practical applications in molecular docking simulations using FFR models. PMID:24564276

  8. Molecularly Imprinted Polymer Based Sensor for the Detection of Theophylline

    NASA Astrophysics Data System (ADS)

    Braga, Guilherme S.; Paterno, Leonardo G.; Fonseca, Fernando J.; del Valle, Manel

    2011-11-01

    A molecularly imprinted polymer (MIP) impedance-based sensor was employed to detect theophylline in distilled water. To evaluate its sensibility, impedance measurements were carried out in a diluted solution of theophylline (1 mM) and distilled water using MIP and NIP (reference non-imprinted polymer) sensors. MIP showed higher sensitivity to theophylline than the NIP. This feature shows their suitability for developing an electronic tongue system for determination of methylxanthines.

  9. Phylogeny of Kinorhyncha Based on Morphology and Two Molecular Loci

    PubMed Central

    Sørensen, Martin V.; Dal Zotto, Matteo; Rho, Hyun Soo; Herranz, Maria; Sánchez, Nuria; Pardos, Fernando; Yamasaki, Hiroshi

    2015-01-01

    rRNA had been omitted. Analysis of the morphological data produced results that were similar with those from the combined molecular and morphological analysis. E.g., the morphological data also supported exclusion of Dracoderes from Cyclorhagida. The main differences between the morphological analysis and analyses based on the combined datasets include: 1) Homalorhagida appears as monophyletic in the morphological tree only, 2) the morphological analyses position Franciscideres and the new genus within Cyclorhagida near Zelinkaderidae and Cateriidae, whereas analyses including molecular data place the two genera inside Allomalorhagida, and 3) species of Campyloderes appear in a basal trichotomy within Kentrorhagata in the morphological tree, whereas analysis of the combined datasets places species of Campyloderes as a sister clade to Echinoderidae and Kentrorhagata. PMID:26200115

  10. Phylogeny of Kinorhyncha Based on Morphology and Two Molecular Loci.

    PubMed

    Sørensen, Martin V; Dal Zotto, Matteo; Rho, Hyun Soo; Herranz, Maria; Sánchez, Nuria; Pardos, Fernando; Yamasaki, Hiroshi

    2015-01-01

    RNA had been omitted. Analysis of the morphological data produced results that were similar with those from the combined molecular and morphological analysis. E.g., the morphological data also supported exclusion of Dracoderes from Cyclorhagida. The main differences between the morphological analysis and analyses based on the combined datasets include: 1) Homalorhagida appears as monophyletic in the morphological tree only, 2) the morphological analyses position Franciscideres and the new genus within Cyclorhagida near Zelinkaderidae and Cateriidae, whereas analyses including molecular data place the two genera inside Allomalorhagida, and 3) species of Campyloderes appear in a basal trichotomy within Kentrorhagata in the morphological tree, whereas analysis of the combined datasets places species of Campyloderes as a sister clade to Echinoderidae and Kentrorhagata. PMID:26200115

  11. Design of two and three input molecular logic gates using non-Watson-Crick base pairing-based molecular beacons.

    PubMed

    Lin, Jia-Hui; Tseng, Wei-Lung

    2014-03-21

    This study presents a single, resettable, and sensitive molecular beacon (MB) used to operate molecular-scale logic gates. The MB consists of a random DNA sequence, a fluorophore at the 5'-end, and a quencher at the 3'-end. The presence of Hg(2+), Ag(+), and coralyne promoted the formation of stable T-Hg(2+)-T, C-Ag(+)-C, and A2-coralyne-A2 coordination in the MB probe, respectively, thereby driving its conformational change. The metal ion or small molecule-mediated coordination of mismatched DNA brought the fluorophore and the quencher into close proximity, resulting in collisional quenching of fluorescence between the two organic dyes. Because thiol can bind Hg(2+) and remove it from the T-Hg(2+)-T-based MB, adding thiol to a solution of the T-Hg(2+)-T-based MB allowed the fluorophore and the quencher to be widely separated. A similar phenomenon was observed when replacing Hg(2+) with Ag(+). Because Ag(+) strongly binds to iodide, cyanide, and cysteine, they were capable of removing Ag(+) from the C-Ag(+)-C-based MB, restoring the fluorescence of the MB. Moreover, the fluorescence of the A2-coralyne-A2-based MB could be switched on by adding polyadenosine. Using these analytes as inputs and the MB as a signal transducer, we successfully developed a series of two-input, three-input, and set-reset logic gates at the molecular level.

  12. Paper-based molecular diagnostic for Chlamydia trachomatis

    PubMed Central

    Linnes, Jacqueline C.; Fan, Andy; Rodriguez, Natalia M.; Lemieux, Bertrand; Kong, Huimin; Klapperich, Catherine M.

    2014-01-01

    Herein we show the development of a minimally instrumented paper-based molecular diagnostic for point of care detection of sexually transmitted infections caused by Chlamydia trachomatis. This new diagnostic platform incorporates cell lysis, isothermal nucleic acid amplification, and lateral flow visual detection using only a pressure source and heat block, eliminating the need for expensive laboratory equipment. This paper-based test can be performed in less than one hour and has a clinically relevant limit of detection that is 100x more sensitive than current rapid immunoassays used for chlamydia diagnosis. PMID:25309740

  13. Molecular Beacon CNT-based Detection of SNPs

    NASA Astrophysics Data System (ADS)

    Egorova, V. P.; Krylova, H. V.; Lipnevich, I. V.; Veligura, A. A.; Shulitsky, B. G.; Y Fedotenkova, L.

    2015-11-01

    An fluorescence quenching effect due to few-walled carbon nanotubes chemically modified by carboxyl groups has been utilized to discriminate Single Nucleotide Polymorphism (SNP). It was shown that the complex obtained from these nanotube and singlestranded primer DNA is formed due to stacking interactions between the hexagons of the nanotubes and aromatic rings of nucleotide bases as well as due to establishing of hydrogen bonds between acceptor amine groups of nucleotide bases and donor carboxyl groups of the nanotubes. It has been demonstrated that these complexes may be used to make highly effective DNA biosensors detecting SNPs which operate as molecular beacons.

  14. Kinetic modeling based probabilistic segmentation for molecular images.

    PubMed

    Saad, Ahmed; Hamarneh, Ghassan; Möller, Torsten; Smith, Ben

    2008-01-01

    We propose a semi-supervised, kinetic modeling based segmentation technique for molecular imaging applications. It is an iterative, self-learning algorithm based on uncertainty principles, designed to alleviate low signal-to-noise ratio (SNR) and partial volume effect (PVE) problems. Synthetic fluorodeoxyglucose (FDG) and simulated Raclopride dynamic positron emission tomography (dPET) brain images with excessive noise levels are used to validate our algorithm. We show, qualitatively and quantitatively, that our algorithm outperforms state-of-the-art techniques in identifying different functional regions and recovering the kinetic parameters.

  15. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine.

    PubMed

    Jain, Ajay N

    2003-02-13

    Surflex is a fully automatic flexible molecular docking algorithm that combines the scoring function from the Hammerhead docking system with a search engine that relies on a surface-based molecular similarity method as a means to rapidly generate suitable putative poses for molecular fragments. Results are presented evaluating reliability and accuracy of dockings compared with crystallographic experimental results on 81 protein/ligand pairs of substantial structural diversity. In over 80% of the complexes, Surflex's highest scoring docked pose was within 2.5 A root-mean-square deviation (rmsd), with over 90% of the complexes having one of the top ranked poses within 2.5 A rmsd. Results are also presented assessing Surflex's utility as a screening tool on two protein targets (thymidine kinase and estrogen receptor) using data sets on which competing methods were run. Performance of Surflex was significantly better, with true positive rates of greater than 80% at false positive rates of less than 1%. Docking time was roughly linear in number of rotatable bonds, beginning with a few seconds for rigid molecules and adding approximately 10 s per rotatable bond.

  16. A molecular beacon assay for measuring base excision repair activities.

    PubMed

    Maksimenko, Andrei; Ishchenko, Alexander A; Sanz, Guenhaël; Laval, Jacques; Elder, Rhoderick H; Saparbaev, Murat K

    2004-06-18

    The base excision repair (BER) pathway plays a key role in protecting the genome from endogenous DNA damage. Current methods to measure BER activities are indirect and cumbersome. Here, we introduce a direct method to assay DNA excision repair that is suitable for automation and industrial use, based on the fluorescence quenching mechanism of molecular beacons. We designed a single-stranded DNA oligonucleotide labelled with a 5'-fluorescein (F) and a 3'-Dabcyl (D) in which the fluorophore, F, is held in close proximity to the quencher, D, by the stem-loop structure design of the oligonucleotide. Following removal of the modified base or incision of the oligonucleotide, the fluorophore is separated from the quencher and fluorescence can be detected as a function of time. Several modified beacons have been used to validate the assay on both cell-free extracts and purified proteins. We have further developed the method to analyze BER in cultured cells. As described, the molecular beacon-based assay can be applied to all DNA modifications processed by DNA excision/incision repair pathways. Possible applications of the assay are discussed, including high-throughput real-time DNA repair measurements both in vitro and in living cells.

  17. A Molecular Imaging Approach to Mercury Sensing Based on Hyperpolarized (129)Xe Molecular Clamp Probe.

    PubMed

    Guo, Qianni; Zeng, Qingbin; Jiang, Weiping; Zhang, Xiaoxiao; Luo, Qing; Zhang, Xu; Bouchard, Louis-S; Liu, Maili; Zhou, Xin

    2016-03-14

    Mercury pollution, in the form of mercury ions (Hg(2+)), is a major health and environmental hazard. Commonly used sensors are invasive and limited to point measurements. Fluorescence-based sensors do not provide depth resolution needed to image spatial distributions. Herein we report a novel sensor capable of yielding spatial distributions by MRI using hyperpolarized (129)Xe. A molecular clamp probe was developed consisting of dipyrrolylquinoxaline (DPQ) derivatives and twocryptophane-A cages. The DPQ derivatives act as cation receptors whereas cryptophane-A acts as a suitable host molecule for xenon. When the DPQ moiety interacts with mercury ions, the molecular clamp closes on the ion. Due to overlap of the electron clouds of the two cryptophane-A cages, the shielding effect on the encapsulated Xe becomes important. This leads to an upfield change of the chemical shift of the encapsulated Xe. This sensor exhibits good selectivity and sensitivity toward the mercury ion. This mercury-activated hyperpolarized (129)Xe-based chemosensor is a new concept method for monitoring Hg(2+) ion distributions by MRI.

  18. Recent Advances of Radionuclide-based Molecular Imaging of Atherosclerosis

    PubMed Central

    Kazuma, Soraya M.; Sultan, Deborah; Zhao, Yongfeng; Detering, Lisa; You, Meng; Luehmann, Hannah P.; Abdalla, Dulcineia S.P.; Liu, Yongjian

    2015-01-01

    Atherosclerosis is a systemic disease characterized by the development of multifocal plaque lesions within vessel walls and extending into the vascular lumen. The disease takes decades to develop symptomatic lesions, affording opportunities for accurate detection of plaque progression, analysis of risk factors responsible for clinical events, and planning personalized treatment. Of the available molecular imaging modalities, radionuclide-based imaging strategies have been favored due to their sensitivity, quantitative detection and pathways for translational research. This review summarizes recent advances of radiolabeled small molecules, peptides, antibodies and nanoparticles for atherosclerotic plaque imaging during disease progression. PMID:26369676

  19. Molecular Dipole Osmosis Based on Induced Charge Electro-Osmosis

    NASA Astrophysics Data System (ADS)

    Sugioka, Hideyuki

    2016-09-01

    We propose a novel mechanism of producing a large nonlinear electrokinetic vortex flow around a nonconductive polar molecule in an electrolyte. That is, a large nonlinear electrokinetic slip velocity is derived by considering a local giant permittivity due to a molecular electric dipole moment with induced-charge electro-osmosis (ICEO). Different from the conventional ICEO theory, our theory predicts that a nonconductive biomaterial, such as a base of a deoxyribonucleic acid (DNA) molecule, has a significantly high ICEO flow velocity because of its large local permittivity. We consider that our findings will contribute markedly to promising biomedical applications.

  20. Recent advances on polyoxometalate-based molecular and composite materials.

    PubMed

    Song, Yu-Fei; Tsunashima, Ryo

    2012-11-21

    Polyoxometalates (POMs) are a subset of metal oxides with unique physical and chemical properties, which can be reliably modified through various techniques and methods to develop sophisticated materials and devices. In parallel with the large number of new crystal structures reported in the literature, the application of these POMs towards multifunctional materials has attracted considerable attention. This critical review summarizes recent progress on POM-based molecular and composite materials, and particularly highlights the emerging areas that are closely related to surface, electronic, energy, environment, life science, etc. (171 references). PMID:22850732

  1. Molecular tools for the construction of peptide-based materials.

    PubMed

    Ramakers, B E I; van Hest, J C M; Löwik, D W P M

    2014-04-21

    Proteins and peptides are fundamental components of living systems where they play crucial roles at both functional and structural level. The versatile biological properties of these molecules make them interesting building blocks for the construction of bio-active and biocompatible materials. A variety of molecular tools can be used to fashion the peptides necessary for the assembly of these materials. In this tutorial review we shall describe five of the main techniques, namely solid phase peptide synthesis, native chemical ligation, Staudinger ligation, NCA polymerisation, and genetic engineering, that have been used to great effect for the construction of a host of peptide-based materials.

  2. DNA barcode-based molecular identification system for fish species.

    PubMed

    Kim, Sungmin; Eo, Hae-Seok; Koo, Hyeyoung; Choi, Jun-Kil; Kim, Won

    2010-12-01

    In this study, we applied DNA barcoding to identify species using short DNA sequence analysis. We examined the utility of DNA barcoding by identifying 53 Korean freshwater fish species, 233 other freshwater fish species, and 1339 saltwater fish species. We successfully developed a web-based molecular identification system for fish (MISF) using a profile hidden Markov model. MISF facilitates efficient and reliable species identification, overcoming the limitations of conventional taxonomic approaches. MISF is freely accessible at http://bioinfosys.snu.ac.kr:8080/MISF/misf.jsp .

  3. Estrellas jóvenes en la nube molecular del Camaleón II

    NASA Astrophysics Data System (ADS)

    Chavero, C.; Mazzalay, X.; Paz, D.; Quinzio, B.; Racca, G.; Sales, L.; Stasyszyn, F.; Ahumada, A.; Gómez, M.

    We present optical spectra of three candidate young stellar objects in the Chamaeleon II dark cloud. The observations were carried out at the CASLEO with the REOSC (DS) spectrograph, covering a spectral range between 5000 < λ < 8000 Å. These objects were selected from two lists of candidate young stars proposed by Larson et al. (1998, A&A 337:465) and Voung et al. (2001, A&A 379:208) based on the infrared excesses. We find Hα in emission in two of the three objects. This is an indicator of the pre-main sequence evolutionary state of a star. In addition, for one of the objects with Hα in emission we detect the TiO absorption bands (6180 and 7100 Å), characteristic of the M spectral type. The nature of the third object remains uncertain and higher signal to noise spectra are required to clarify its evolutionary status.

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

    PubMed

    Müller, Klaus

    2014-01-01

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

  5. Single-molecular diodes based on opioid derivatives.

    PubMed

    Siqueira, M R S; Corrêa, S M; Gester, R M; Del Nero, J; Neto, A M J C

    2015-12-01

    We propose an efficient single-molecule rectifier based on a derivative of opioid. Electron transport properties are investigated within the non-equilibrium Green's function formalism combined with density functional theory. The analysis of the current-voltage characteristics indicates obvious diode-like behavior. While heroin presents rectification coefficient R>1, indicating preferential electronic current from electron-donating to electron-withdrawing, 3 and 6-acetylmorphine and morphine exhibit contrary behavior, R<1. Our calculations indicate that the simple inclusion of acetyl groups modulate a range of devices, which varies from simple rectifying to resonant-tunneling diodes. In particular, the rectification rations for heroin diodes show microampere electron current with a maximum of rectification (R=9.1) at very low bias voltage of ∼0.6 V and (R=14.3)∼1.8 V with resistance varying between 0.4 and 1.5 M Ω. Once most of the current single-molecule diodes usually rectifies in nanoampere, are not stable over 1.0 V and present electrical resistance around 10 M. Molecular devices based on opioid derivatives are promising in molecular electronics.

  6. Single-molecular diodes based on opioid derivatives.

    PubMed

    Siqueira, M R S; Corrêa, S M; Gester, R M; Del Nero, J; Neto, A M J C

    2015-12-01

    We propose an efficient single-molecule rectifier based on a derivative of opioid. Electron transport properties are investigated within the non-equilibrium Green's function formalism combined with density functional theory. The analysis of the current-voltage characteristics indicates obvious diode-like behavior. While heroin presents rectification coefficient R>1, indicating preferential electronic current from electron-donating to electron-withdrawing, 3 and 6-acetylmorphine and morphine exhibit contrary behavior, R<1. Our calculations indicate that the simple inclusion of acetyl groups modulate a range of devices, which varies from simple rectifying to resonant-tunneling diodes. In particular, the rectification rations for heroin diodes show microampere electron current with a maximum of rectification (R=9.1) at very low bias voltage of ∼0.6 V and (R=14.3)∼1.8 V with resistance varying between 0.4 and 1.5 M Ω. Once most of the current single-molecule diodes usually rectifies in nanoampere, are not stable over 1.0 V and present electrical resistance around 10 M. Molecular devices based on opioid derivatives are promising in molecular electronics. PMID:26613894

  7. Implementation of CCNUGrid-based Computational Environment for Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Luo, Changhua; Ren, Yanliang; Wan, Jian; Xu, Xin

    2007-12-01

    Grid computing technology has being regarded as one of the most promising solutions for the tremendous requirement of computing resources in the field of molecular modeling up to date. Contrast to building a more and more powerful super-computer with novel hardware in a local network, grid technology enable us, in principle, to integrate various previous and present computing resources located in different location into a computing platform as a whole. As a case demonstration, we reported herein that a campus grid entitled CCNUGrid was implemented with grid middleware, consisting of four local computing networks distributed in College of Chemistry, College of Physics, Center for Network, and Center for Education Information Technology and Engineering, respectively, at Central China Normal University. Visualization functions of monitoring computer machines in each local network, monitoring job processing flow, and monitoring computational results were realized in this campus grid-based computational environment, in addition to the conventional components of grid architecture: universal portal, task management, computing node and security. In the last section of this paper, a molecular docking-based virtual screening study was performed at the CCNUGrid, as one example of CCNUGrid applications.

  8. Improving structure-based function prediction using molecular dynamics

    PubMed Central

    Glazer, Dariya S.; Radmer, Randall J.; Altman, Russ B.

    2009-01-01

    Summary The number of molecules with solved three-dimensional structure but unknown function is increasing rapidly. Particularly problematic are novel folds with little detectable similarity to molecules of known function. Experimental assays can determine the functions of such molecules, but are time-consuming and expensive. Computational approaches can identify potential functional sites; however, these approaches generally rely on single static structures and do not use information about dynamics. In fact, structural dynamics can enhance function prediction: we coupled molecular dynamics simulations with structure-based function prediction algorithms that identify Ca2+ binding sites. When applied to 11 challenging proteins, both methods showed substantial improvement in performance, revealing 22 more sites in one case and 12 more in the other, with a modest increase in apparent false positives. Thus, we show that treating molecules as dynamic entities improves the performance of structure-based function prediction methods. PMID:19604472

  9. Enzymatic amplification detection of DNA based on "molecular beacon" biosensors.

    PubMed

    Mao, Xun; Jiang, Jianhui; Xu, Xiangmin; Chu, Xia; Luo, Yan; Shen, Guoli; Yu, Ruqin

    2008-05-15

    We described a novel electrochemical DNA biosensor based on molecular beacon (MB) probe and enzymatic amplification protocol. The MB modified with a thiol at its 5' end and a biotin at its 3' end was immobilized on the gold electrode through mixed self-assembly process. Hybridization events between MB and target DNA cause the conformational change of the MB, triggering the attached biotin group on the electrode surface. Following the specific interaction between the conformation-triggered biotin and streptavidin-horseradish peroxidase (HRP), subsequent quantification of DNA was realized by electrochemical detection of enzymatic product in the presence of substrate. The detection limit is obtained as low as 0.1nM. The presented DNA biosensor has good selectivity, being able to differentiate between a complementary target DNA sequence and one containing G-G single-base mismatches.

  10. Molecular based subtyping of feline mammary carcinomas and clinicopathological characterization.

    PubMed

    Soares, Maria; Madeira, Sara; Correia, Jorge; Peleteiro, Maria; Cardoso, Fátima; Ferreira, Fernando

    2016-06-01

    Molecular classification of feline mammary carcinomas (FMC) from which specific behavioral patterns may be estimated has potential applications in veterinary clinical practice and in comparative oncology. In this perspective, the main goal of this study was to characterize both the clinical and the pathological features of the different molecular phenotypes found in a population of FMC (n = 102), using the broadly accepted IHC-based classification established by St. Gallen International Expert Consensus panel. The luminal B/HER2-negative subtype was the most common (29.4%, 30/102) followed by luminal B/HER2-positive subtype (19.6%, 20/102), triple negative basal-like (16.7%, 17/102), luminal A (14.7%, 15/102), triple negative normal-like (12.7%, 13/102) and finally, HER2-positive subtype (6.9%, 7/102). Luminal A subtype was significantly associated with smaller tumors (p = 0.024) and with well differentiated ones (p < 0.001), contrasting with the triple negative basal-like subtype, that was associated with larger and poorly differentiated tumors (p < 0.001), and with the presence of necrotic areas in the tumoral lesion (p = 0.003). In the survival analysis, cats with Luminal A subtype presented the highest survival time (mean OS = 943.6 days) and animals with triple negative basal-like subtype exhibited the lowest survival time (OS mean = 368.9 days). Moreover, two thirds (64%, 32/50) of the queens with multiple primary tumors showed different molecular subtypes in each carcinoma, revealing that all independent lesions should be analyzed in order to improve the clinical management of animals. Finally, the similarities between the subtypes of feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies. PMID:27212699

  11. Graphene-based nanomaterials as molecular imaging agents.

    PubMed

    Garg, Bhaskar; Sung, Chu-Hsun; Ling, Yong-Chien

    2015-01-01

    Molecular imaging (MI) is a noninvasive, real-time visualization of biochemical events at the cellular and molecular level within tissues, living cells, and/or intact objects that can be advantageously applied in the areas of diagnostics, therapeutics, drug discovery, and development in understanding the nanoscale reactions including enzymatic conversions and protein-protein interactions. Consequently, over the years, great advancement has been made in the development of a variety of MI agents such as peptides, aptamers, antibodies, and various nanomaterials (NMs) including single-walled carbon nanotubes. Recently, graphene, a material popularized by Geim & Novoselov, has ignited considerable research efforts to rationally design and execute a wide range of graphene-based NMs making them an attractive platform for developing highly sensitive MI agents. Owing to their exceptional physicochemical and biological properties combined with desirable surface engineering, graphene-based NMs offer stable and tunable visible emission, small hydrodynamic size, low toxicity, and high biocompatibility and thus have been explored for in vitro and in vivo imaging applications as a promising alternative of traditional imaging agents. This review begins by describing the intrinsic properties of graphene and the key MI modalities. After which, we provide an overview on the recent advances in the design and development as well as physicochemical properties of the different classes of graphene-based NMs (graphene-dye conjugates, graphene-antibody conjugates, graphene-nanoparticle composites, and graphene quantum dots) being used as MI agents for potential applications including theranostics. Finally, the major challenges and future directions in the field will be discussed.

  12. Molecular Dynamics and Energy Minimization Based on Embedded Atom Method

    1995-03-01

    This program performs atomic scale computer simulations of the structure and dynamics of metallic system using energetices based on the Embedded Atom Method. The program performs two types of calculations. First, it performs local energy minimization of all atomic positions to determine ground state and saddle point energies and structures. Second, it performs molecular dynamics simulations to determine thermodynamics or miscroscopic dynamics of the system. In both cases, various constraints can be applied to themore » system. The volume of the system can be varied automatically to achieve any desired external pressure. The temperature in molecular dynamics simulations can be controlled by a variety of methods. Further, the temperature control can be applied either to the entire system or just a subset of the atoms that would act as a thermal source/sink. The motion of one or more of the atoms can be constrained to either simulate the effects of bulk boundary conditions or to facilitate the determination of saddle point configurations. The simulations are performed with periodic boundary conditions.« less

  13. Toward Understanding the Molecular Bases of Stretch Activation

    PubMed Central

    Sanfelice, Domenico; Sanz-Hernández, Máximo; de Simone, Alfonso; Bullard, Belinda; Pastore, Annalisa

    2016-01-01

    Muscles are usually activated by calcium binding to the calcium sensory protein troponin-C, which is one of the three components of the troponin complex. However, in cardiac and insect flight muscle activation is also produced by mechanical stress. Little is known about the molecular bases of this calcium-independent activation. In Lethocerus, a giant water bug often used as a model system because of its large muscle fibers, there are two troponin-C isoforms, called F1 and F2, that have distinct roles in activating the muscle. It has been suggested that this can be explained either by differences in structural features or by differences in the interactions with other proteins. Here we have compared the structural and dynamic properties of the two proteins and shown how they differ. We have also mapped the interactions of the F2 isoform with peptides spanning the sequence of its natural partner, troponin-I. Our data have allowed us to build a model of the troponin complex and may eventually help in understanding the specialized function of the F1 and F2 isoforms and the molecular mechanism of stretch activation. PMID:27226601

  14. A molecularly based theory for electron transfer reorganization energy

    SciTech Connect

    Zhuang, Bilin; Wang, Zhen-Gang

    2015-12-14

    Using field-theoretic techniques, we develop a molecularly based dipolar self-consistent-field theory (DSCFT) for charge solvation in pure solvents under equilibrium and nonequilibrium conditions and apply it to the reorganization energy of electron transfer reactions. The DSCFT uses a set of molecular parameters, such as the solvent molecule’s permanent dipole moment and polarizability, thus avoiding approximations that are inherent in treating the solvent as a linear dielectric medium. A simple, analytical expression for the free energy is obtained in terms of the equilibrium and nonequilibrium electrostatic potential profiles and electric susceptibilities, which are obtained by solving a set of self-consistent equations. With no adjustable parameters, the DSCFT predicts activation energies and reorganization energies in good agreement with previous experiments and calculations for the electron transfer between metallic ions. Because the DSCFT is able to describe the properties of the solvent in the immediate vicinity of the charges, it is unnecessary to distinguish between the inner-sphere and outer-sphere solvent molecules in the calculation of the reorganization energy as in previous work. Furthermore, examining the nonequilibrium free energy surfaces of electron transfer, we find that the nonequilibrium free energy is well approximated by a double parabola for self-exchange reactions, but the curvature of the nonequilibrium free energy surface depends on the charges of the electron-transferring species, contrary to the prediction by the linear dielectric theory.

  15. Molecular-beacon-based array for sensitive DNA analysis.

    PubMed

    Yao, Gang; Tan, Weihong

    2004-08-15

    Molecular beacon (MB) DNA probes provide a new way for sensitive label-free DNA/protein detection in homogeneous solution and biosensor development. However, a relatively low fluorescence enhancement after the hybridization of the surface-immobilized MB hinders its effective biotechnological applications. We have designed new molecular beacon probes to enable a larger separation between the surface and the surface-bound MBs. Using these MB probes, we have developed a DNA array on avidin-coated cover slips and have improved analytical sensitivity. A home-built wide-field optical setup was used for imaging the array. Our results show that linker length, pH, and ionic strength have obvious effects on the performance of the surface-bound MBs. The fluorescence enhancement of the new MBs after hybridization has been increased from 2 to 5.5. The MB-based DNA array could be used for DNA detection with high sensitivity, enabling simultaneous multiple-target bioanalysis in a variety of biotechnological applications.

  16. Genomic and epigenetic insights into the molecular bases of heterosis.

    PubMed

    Chen, Z Jeffrey

    2013-07-01

    Heterosis, also known as hybrid vigour, is widespread in plants and animals, but the molecular bases for this phenomenon remain elusive. Recent studies in hybrids and allopolyploids using transcriptomic, proteomic, metabolomic, epigenomic and systems biology approaches have provided new insights. Emerging genomic and epigenetic perspectives suggest that heterosis arises from allelic interactions between parental genomes, leading to altered programming of genes that promote the growth, stress tolerance and fitness of hybrids. For example, epigenetic modifications of key regulatory genes in hybrids and allopolyploids can alter complex regulatory networks of physiology and metabolism, thus modulating biomass and leading to heterosis. The conceptual advances could help to improve plant and animal productivity through the manipulation of heterosis.

  17. A test of neutral molecular evolution based on nucleotide data.

    PubMed

    Hudson, R R; Kreitman, M; Aguadé, M

    1987-05-01

    The neutral theory of molecular evolution predicts that regions of the genome that evolve at high rates, as revealed by interspecific DNA sequence comparisons, will also exhibit high levels of polymorphism within species. We present here a conservative statistical test of this prediction based on a constant-rate neutral model. The test requires data from an interspecific comparison of at least two regions of the genome and data on levels of intraspecific polymorphism in the same regions from at least one species. The model is rejected for data from the region encompassing the Adh locus and the 5' flanking sequence of Drosophila melanogaster and Drosophila sechellia. The data depart from the model in a direction that is consistent with the presence of balanced polymorphism in the coding region.

  18. Genomic and epigenetic insights into the molecular bases of heterosis.

    PubMed

    Chen, Z Jeffrey

    2013-07-01

    Heterosis, also known as hybrid vigour, is widespread in plants and animals, but the molecular bases for this phenomenon remain elusive. Recent studies in hybrids and allopolyploids using transcriptomic, proteomic, metabolomic, epigenomic and systems biology approaches have provided new insights. Emerging genomic and epigenetic perspectives suggest that heterosis arises from allelic interactions between parental genomes, leading to altered programming of genes that promote the growth, stress tolerance and fitness of hybrids. For example, epigenetic modifications of key regulatory genes in hybrids and allopolyploids can alter complex regulatory networks of physiology and metabolism, thus modulating biomass and leading to heterosis. The conceptual advances could help to improve plant and animal productivity through the manipulation of heterosis. PMID:23752794

  19. Molecular bases of circadian rhythmicity in renal physiology and pathology

    PubMed Central

    Bonny, Olivier; Vinciguerra, Manlio; Gumz, Michelle L.; Mazzoccoli, Gianluigi

    2013-01-01

    The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental–social cues and physiological–behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time–dependent changes in renal pathology. PMID:23901050

  20. DNA Aptamer Based Nanodrugs: Molecular Engineering for Efficiency

    PubMed Central

    Cansiz, Sena; Zhang, Liqin; Wu, Cuichen; Wu, Yuan; Teng, I-Ting; Hou, Weijia; Wang, Yanyue; Wan, Shuo; Cai, Ren; Jin, Chen; Liu, Qiaoling; Tan, Weihong

    2015-01-01

    In the past two decades, the study of cancer therapy has gradually advanced to the “Nano” era. Numerous novel nanomaterials armed with unique physical properties have been introduced into biomedical research. At the same time, functional nucleic acid molecules, especially aptamers, have aroused broad attention from the biomedical community. Benefiting from the advancement of molecular engineering strategies, it is now feasible to combine the cancer specific recognition capability of aptamers with various other special functions of nanomaterials to develop cancer specific drugs at the nanoscale. Nanodrugs are now offering an unprecedented opportunity to achieve the goal of efficient targeted delivery as well as controlled release. This review highlights some achievements of multiple aptamer-based nanodrug systems which have emerged in recent years, including studies in the infant stage of “proof-of-concept”. PMID:26177853

  1. Molecular Beacon-Based MicroRNA Imaging During Neurogenesis.

    PubMed

    Lee, Jonghwan; Kim, Soonhag

    2016-01-01

    The fluorescence monitoring system for examining endogenous microRNA (miRNA) activity in cellular level provides crucial information on not only understanding a critical role of miRNA involving a variety of biological processes, but also evaluating miRNA expression patterns in a noninvasive manner. In this protocol, we report the details of a new procedure for a molecular beacon-based miRNA monitoring system, which includes the illustration scheme for miRNA detection strategy, exogenous miRNA detection, and measurement of endogenous miRNA expression level during neurogenesis. The fluorescence signal of miR-124a beacon quenched by BHQ2 was gradually recovered as increasing concentration of the miR-124a in tube. The functional work of miR-124a beacon was examined in intracellular environment, allowing for the internalization of the miR-124a beacon by lipofectamine, which resulted in activated fluorescent signals of the miR-124a beacon in the HeLa cells after the addition of synthetic miR-124a. The endogenous miR-124a expression level was detected by miR-124a beacon system during neurogenesis, showing brighter fluorescence intensity in cytoplasmic area of P19 cells after induction of neuronal differentiation by retinoic acid. The molecular beacon based-miRNA detection technique could be applicable to the simultaneous visualization of a variety of miRNA expression patterns using different fluorescence dyes. For the study of examining endogenous miRNA expression level using miRNA-beacon system, if cellular differentiation step is already prepared, transfection step of miR-124a beacon into P19 cells, and acquisition of activated fluorescence signal measured by confocal microscope can be conducted approximately within 6 h.

  2. Chemically engineered graphene-based 2D organic molecular magnet.

    PubMed

    Hong, Jeongmin; Bekyarova, Elena; de Heer, Walt A; Haddon, Robert C; Khizroev, Sakhrat

    2013-11-26

    Carbon-based magnetic materials and structures of mesoscopic dimensions may offer unique opportunities for future nanomagnetoelectronic/spintronic devices. To achieve their potential, carbon nanosystems must have controllable magnetic properties. We demonstrate that nitrophenyl functionalized graphene can act as a room-temperature 2D magnet. We report a comprehensive study of low-temperature magnetotransport, vibrating sample magnetometry (VSM), and superconducting quantum interference (SQUID) measurements before and after radical functionalization. Following nitrophenyl (NP) functionalization, epitaxially grown graphene systems can become organic molecular magnets with ferromagnetic and antiferromagnetic ordering that persists at temperatures above 400 K. The field-dependent, surface magnetoelectric properties were studied using scanning probe microscopy (SPM) techniques. The results indicate that the NP-functionalization orientation and degree of coverage directly affect the magnetic properties of the graphene surface. In addition, graphene-based organic magnetic nanostructures were found to demonstrate a pronounced magneto-optical Kerr effect (MOKE). The results were consistent across different characterization techniques and indicate room-temperature magnetic ordering along preferred graphene orientations in the NP-functionalized samples. Chemically isolated graphene nanoribbons (CINs) were observed along the preferred functionality directions. These results pave the way for future magnetoelectronic/spintronic applications based on promising concepts such as current-induced magnetization switching, magnetoelectricity, half-metallicity, and quantum tunneling of magnetization.

  3. Light-operated machines based on threaded molecular structures.

    PubMed

    Credi, Alberto; Silvi, Serena; Venturi, Margherita

    2014-01-01

    Rotaxanes and related species represent the most common implementation of the concept of artificial molecular machines, because the supramolecular nature of the interactions between the components and their interlocked architecture allow a precise control on the position and movement of the molecular units. The use of light to power artificial molecular machines is particularly valuable because it can play the dual role of "writing" and "reading" the system. Moreover, light-driven machines can operate without accumulation of waste products, and photons are the ideal inputs to enable autonomous operation mechanisms. In appropriately designed molecular machines, light can be used to control not only the stability of the system, which affects the relative position of the molecular components but also the kinetics of the mechanical processes, thereby enabling control on the direction of the movements. This step forward is necessary in order to make a leap from molecular machines to molecular motors.

  4. Boolean logic tree of graphene-based chemical system for molecular computation and intelligent molecular search query.

    PubMed

    Huang, Wei Tao; Luo, Hong Qun; Li, Nian Bing

    2014-05-01

    The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analyzing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable "words" and chemical interactions as "syntax" logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in biosensing, nanotechnology, and drug delivery.

  5. POLYANA-A tool for the calculation of molecular radial distribution functions based on Molecular Dynamics trajectories

    NASA Astrophysics Data System (ADS)

    Dimitroulis, Christos; Raptis, Theophanes; Raptis, Vasilios

    2015-12-01

    We present an application for the calculation of radial distribution functions for molecular centres of mass, based on trajectories generated by molecular simulation methods (Molecular Dynamics, Monte Carlo). When designing this application, the emphasis was placed on ease of use as well as ease of further development. In its current version, the program can read trajectories generated by the well-known DL_POLY package, but it can be easily extended to handle other formats. It is also very easy to 'hack' the program so it can compute intermolecular radial distribution functions for groups of interaction sites rather than whole molecules.

  6. Unveiling the molecular mechanism of brassinosteroids: Insights from structure-based molecular modeling studies.

    PubMed

    Lei, Beilei; Liu, Jiyuan; Yao, Xiaojun

    2015-12-01

    Brassinosteroid (BR) phytohormones play indispensable roles in plant growth and development. Brassinolide (BL) and 24-epibrassinolide (24-epiBL) are the most active ones among the BRs reported thus far. Unfortunately, the extremely low natural content and intricate synthesis process limit their popularization in agricultural production. Earlier reports to discover alternative compounds have resulted in molecules with nearly same scaffold structure and without diversity in chemical space. In the present study, receptors structure based BRs regulation mechanism was analyzed. First, we examined the detailed binding interactions and their dynamic stability between BL and its receptor BRI1 and co-receptor BAK1. Then, the binding modes and binding free energies for 24-epiBL and a series of representative BRs binding with BRI1 and BRI1-BAK1 were carried out by molecular docking, energy minimization and MM-PBSA free energy calculation. The obtained binding structures and energetic results provided vital insights into the structural factors affecting the activity from both receptors and BRs aspects. Subsequently, the obtained knowledge will serve as valuable guidance to build pharmacophore models for rational screening of new scaffold alternative BRs.

  7. A Raman-based endoscopic strategy for multiplexed molecular imaging.

    PubMed

    Zavaleta, Cristina L; Garai, Ellis; Liu, Jonathan T C; Sensarn, Steven; Mandella, Michael J; Van de Sompel, Dominique; Friedland, Shai; Van Dam, Jacques; Contag, Christopher H; Gambhir, Sanjiv S

    2013-06-18

    Endoscopic imaging is an invaluable diagnostic tool allowing minimally invasive access to tissues deep within the body. It has played a key role in screening colon cancer and is credited with preventing deaths through the detection and removal of precancerous polyps. However, conventional white-light endoscopy offers physicians structural information without the biochemical information that would be advantageous for early detection and is essential for molecular typing. To address this unmet need, we have developed a unique accessory, noncontact, fiber optic-based Raman spectroscopy device that has the potential to provide real-time, multiplexed functional information during routine endoscopy. This device is ideally suited for detection of functionalized surface-enhanced Raman scattering (SERS) nanoparticles as molecular imaging contrast agents. This device was designed for insertion through a clinical endoscope and has the potential to detect and quantify the presence of a multiplexed panel of tumor-targeting SERS nanoparticles. Characterization of the Raman instrument was performed with SERS particles on excised human tissue samples, and it has shown unsurpassed sensitivity and multiplexing capabilities, detecting 326-fM concentrations of SERS nanoparticles and unmixing 10 variations of colocalized SERS nanoparticles. Another unique feature of our noncontact Raman endoscope is that it has been designed for efficient use over a wide range of working distances from 1 to 10 mm. This is necessary to accommodate for imperfect centering during endoscopy and the nonuniform surface topology of human tissue. Using this endoscope as a key part of a multiplexed detection approach could allow endoscopists to distinguish between normal and precancerous tissues rapidly and to identify flat lesions that are otherwise missed.

  8. Molecular Sentinel-on-Chip for SERS-Based Biosensing†

    PubMed Central

    Du, Yan; Batchelor, Dale; Leonard, Donovan N.; Misra, Veena; Vo-Dinh, Tuan

    2013-01-01

    The development of DNA detection techniques on large-area plasmonics-active platforms is critical for many medical applications such as high-throughput screening, medical diagnosis and systems biology research. Here, we report for the first time a unique “molecular sentinel-on-chip” (MSC) technology for surface-enhanced Raman scattering (SERS)-based DNA detection. This unique approach allows label-free detection of DNA molecules on chips developed on a wafer scale using large area nanofabrication methodologies. To develop plasmonics-active biosensing platforms in a repeatable and reproducible manner, we employed a combination of deep UV lithography, atomic layer deposition, and metal deposition to fabricate triangular-shaped nanowire (TSNW) arrays having controlled sub-10 nm gaps nanostructures over an entire 6-inch wafer. The detection of a DNA sequence of the Ki-67 gene, a critical breast cancer biomarker, on the TSNW substrate illustrates the usefulness and potential of the MSC technology as a novel SERS-based DNA detection method. PMID:23493773

  9. Pathological bases for a robust application of cancer molecular classification.

    PubMed

    Diaz-Cano, Salvador J

    2015-01-01

    Any robust classification system depends on its purpose and must refer to accepted standards, its strength relying on predictive values and a careful consideration of known factors that can affect its reliability. In this context, a molecular classification of human cancer must refer to the current gold standard (histological classification) and try to improve it with key prognosticators for metastatic potential, staging and grading. Although organ-specific examples have been published based on proteomics, transcriptomics and genomics evaluations, the most popular approach uses gene expression analysis as a direct correlate of cellular differentiation, which represents the key feature of the histological classification. RNA is a labile molecule that varies significantly according with the preservation protocol, its transcription reflect the adaptation of the tumor cells to the microenvironment, it can be passed through mechanisms of intercellular transference of genetic information (exosomes), and it is exposed to epigenetic modifications. More robust classifications should be based on stable molecules, at the genetic level represented by DNA to improve reliability, and its analysis must deal with the concept of intratumoral heterogeneity, which is at the origin of tumor progression and is the byproduct of the selection process during the clonal expansion and progression of neoplasms. The simultaneous analysis of multiple DNA targets and next generation sequencing offer the best practical approach for an analytical genomic classification of tumors. PMID:25898411

  10. Cell-based quantification of molecular biomarkers in histopathology specimens

    PubMed Central

    Al-Kofahi, Yousef; Lassoued, Wiem; Grama, Kedar; Nath, Sumit K; Zhu, Jianliang; Oueslati, Ridha; Feldman, Michael; Lee, William M F; Roysam, Badrinath

    2011-01-01

    Aims To investigate the use of a computer-assisted technology for objective, cell-based quantification of molecular biomarkers in specified cell types in histopathology specimens, with the aim of advancing current visual estimation or pixel-level (rather than cell-based) quantification methods. Methods and results Tissue specimens were multiplex-immunostained to reveal cell structures, cell type markers, and analytes, and imaged with multispectral microscopy. The image data were processed with novel software that automatically delineates and types each cell in the field, measures morphological features, and quantifies analytes in different subcellular compartments of specified cells. The methodology was validated with the use of cell blocks composed of differentially labelled cultured cells mixed in known proportions, and evaluated on human breast carcinoma specimens for quantifying human epidermal growth factor receptor 2, oestrogen receptor, progesterone receptor, Ki67, phospho-extracellular signal-related kinase, and phospho-S6. Automated cell-level analyses closely matched human assessments, but, predictably, differed from pixel-level analyses of the same images. Conclusions Our method reveals the type, distribution, morphology and biomarker state of each cell in the field, and allows multiple biomarkers to be quantified over specified cell types, regardless of abundance. It is ideal for studying specimens from patients in clinical trials of targeted therapeutic agents, for investigating minority stromal cell subpopulations, and for phenotypic characterization to personalize therapy and prognosis. PMID:21771025

  11. Arrays of high quality SAM-based junctions and their application in molecular diode based logic.

    PubMed

    Wan, Albert; Suchand Sangeeth, C S; Wang, Lejia; Yuan, Li; Jiang, Li; Nijhuis, Christian A

    2015-12-14

    This paper describes a method to fabricate a microfluidic top-electrode that can be utilized to generate arrays of self-assembled monolayer (SAM)-based junctions. The top-electrodes consist of a liquid-metal of GaOx/EGaIn mechanically stabilized in microchannels and through-holes in polydimethylsiloxane (PDMS); these top-electrodes form molecular junctions by directly placing them onto the SAM supported by template-stripped (TS) Ag or Au bottom-electrodes. Unlike conventional techniques to form multiple junctions, our method does not require lithography to pattern the bottom-electrode and is compatible with TS bottom-electrodes, which are ultra-flat with large grains, free from potential contamination of photoresist residues, and do not have electrode-edges where the molecules are unable to pack well. We formed tunneling junctions with n-alkanethiolate SAMs in yields of ∼80%, with good reproducibility and electrical stability. Temperature dependent J(V) measurements indicated that the mechanism of charge transport across the junction is coherent tunneling. To demonstrate the usefulness of these junctions, we formed molecular diodes based on SAMs with Fc head groups. These junctions rectify currents with a rectification ratio R of 45. These molecular diodes were incorporated in simple electronic circuitry to demonstrate molecular diode-based Boolean logic.

  12. Postiive tone resists based on network deploymerization of molecular resists

    NASA Astrophysics Data System (ADS)

    Lawson, Richard A.; Cheng, Jing; Cheshmehkani, Ameneh; Tolbert, Laren M.; Henderson, Clifford L.

    2013-03-01

    Conventional chemically amplified resists have several issues that can potentially limit their capability for sub-40 nm imaging. One of the major issues at this size scale is that the mechanical strength of positive tone CARs limits the amount of stress they can withstand during development, rinse, and drying, thus leading to problems with pattern collapse due to the high capillary forces generated during drying. This problem is exasperated by the fact that linear polymers show dramatically reduced modulus at sub-50 nm features sizes. To improve on this problem, we have made a positive tone resist based on network depolymerization of molecular resists. The resist thermally cross-links after being spin cast into thin film form through reactions between vinyl ether groups and carboxylic acid groups. By cross-linking the resist to form a dense three dimensional polymer network, the mechanical strength of the resist is greatly improved compared to linear polymers. The network is depolymerized using an acid catalyzed reaction to create development contrast that allows for patterning of the resist via development in either aqueous base or organic solvent. One drawback of the current resist design is that the free carboxylic acids on the resist molecule appear to react in solution at room temperature with both the vinyl ether groups on adjacent molecules and with any added base quencher. These reactions cause reduced effectiveness of the base quencher and produce a noticeable resist shelf life problem. Despite these limitations, the material was used to compare the effect of development in aqueous base versus organic solvent. The resist formulated in this work showed a DUV sensitivity of 7 mJ/cm2 and a contrast of 5.2 for development in either solvent or aqueous base. Under 100 keV e-beam imaging, the material showed 40 nm resolution for both development types. In standard 0.26 N TMAH, the dose-to-size was 84 μC/cm2 with 3σ LER of 14.2 nm. Using methyl isobutyl ketone

  13. Conductivity of carbon-based molecular junctions from ab-initio methods

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Fei; Luo, Yi

    2014-12-01

    Carbon nanomaterials (CNMs) are prompting candidates for next generational electronics. In this review we provide a mini overview of recent results on the conductivity of carbon-based molecular junctions obtained from ab-initio methods. CNMs used as nanoelectrodes and molecular materials in molecular junctions are discussed. The functionalities that include the nanomechanically controlled molecular conductance switches, negative differential resistance devices, and electronic rectifiers realized by using CNMs have been demonstrated.

  14. Interfacial activation-based molecular bioimprinting of lipolytic enzymes.

    PubMed Central

    Mingarro, I; Abad, C; Braco, L

    1995-01-01

    Interfacial activation-based molecular (bio)-imprinting (IAMI) has been developed to rationally improve the performance of lipolytic enzymes in nonaqueous environments. The strategy combinedly exploits (i) the known dramatic enhancement of the protein conformational rigidity in a water-restricted milieu and (ii) the reported conformational changes associated with the activation of these enzymes at lipid-water interfaces, which basically involves an increased substrate accessibility to the active site and/or an induction of a more competent catalytic machinery. Six model enzymes have been assayed in several model reactions in nonaqueous media. The results, rationalized in light of the present biochemical and structural knowledge, show that the IAMI approach represents a straightforward, versatile method to generate manageable, activated (kinetically trapped) forms of lipolytic enzymes, providing under optimal conditions nonaqueous rate enhancements of up to two orders of magnitude. It is also shown that imprintability of lipolytic enzymes depends not only on the nature of the enzyme but also on the "quality" of the interface used as the template. PMID:7724558

  15. Molecular and Cellular Bases of Iron Metabolism in Humans.

    PubMed

    Milto, I V; Suhodolo, I V; Prokopieva, V D; Klimenteva, T K

    2016-06-01

    Iron is a microelement with the most completely studied biological functions. Its wide dissemination in nature and involvement in key metabolic pathways determine the great importance of this metal for uni- and multicellular organisms. The biological role of iron is characterized by its indispensability in cell respiration and various biochemical processes providing normal functioning of cells and organs of the human body. Iron also plays an important role in the generation of free radicals, which under different conditions can be useful or damaging to biomolecules and cells. In the literature, there are many reviews devoted to iron metabolism and its regulation in pro- and eukaryotes. Significant progress has been achieved recently in understanding molecular bases of iron metabolism. The purpose of this review is to systematize available data on mechanisms of iron assimilation, distribution, and elimination from the human body, as well as on its biological importance and on the major iron-containing proteins. The review summarizes recent ideas about iron metabolism. Special attention is paid to mechanisms of iron absorption in the small intestine and to interrelationships of cellular and extracellular pools of this metal in the human body.

  16. Sensitive determination of citrinin based on molecular imprinted electrochemical sensor

    NASA Astrophysics Data System (ADS)

    Atar, Necip; Yola, Mehmet Lütfi; Eren, Tanju

    2016-01-01

    In this report, a novel molecular imprinted voltammetric sensor based on glassy carbon electrode (GCE) modified with platinum nanoparticles (PtNPs) involved in a polyoxometalate (H3PW12O40, POM) functionalized reduced graphene oxide (rGO) was prepared for the determination of citrinin (CIT). The developed surfaces were characterized by using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. CIT imprinted GCE was prepared via electropolymerization process of 80.0 mM pyrrole as monomer in the presence of phosphate buffer solution (pH 6.0) containing 20.0 mM CIT. The linearity range and the detection limit of the developed method were calculated as 1.0 × 10-12-1.0 × 10-10 M and 2.0 × 10-13 M, respectively. In addition, the voltammetric sensor was applied to rye samples. The stability and selectivity of the voltammetric sensor were also reported.

  17. Actin-based motility propelled by molecular motors

    NASA Astrophysics Data System (ADS)

    Upadyayula, Sai Pramod; Rangarajan, Murali

    2012-09-01

    Actin-based motility of Listeria monocytogenes propelled by filament end-tracking molecular motors has been simulated. Such systems may act as potential nanoscale actuators and shuttles useful in sorting and sensing biomolecules. Filaments are modeled as three-dimensional elastic springs distributed on one end of the capsule and persistently attached to the motile bacterial surface through an end-tracking motor complex. Filament distribution is random, and monomer concentration decreases linearly as a function of position on the bacterial surface. Filament growth rate increases with monomer concentration but decreases with the extent of compression. The growing filaments exert push-pull forces on the bacterial surface. In addition to forces, torques arise due to two factors—distribution of motors on the bacterial surface, and coupling of torsion upon growth due to the right-handed helicity of F-actin—causing the motile object to undergo simultaneous translation and rotation. The trajectory of the bacterium is simulated by performing a force and torque balance on the bacterium. All simulations use a fixed value of torsion. Simulations show strong alignment of the filaments and the long axis of the bacterium along the direction of motion. In the absence of torsion, the bacterial surface essentially moves along the direction of the long axis. When a small amount of the torsion is applied to the bacterial surface, the bacterium is seen to move in right-handed helical trajectories, consistent with experimental observations.

  18. [Cell therapy in cartilage repair: cellular and molecular bases].

    PubMed

    Corvol, Marie-Thérèse; Tahiri, Khadija; Montembault, Alexandra; Daumard, Alain; Savouret, Jean-François; Rannou, François

    2008-01-01

    The destruction of articular cartilage represents the outcome of most inflammatory and degenerative rheumatic diseases and leads to severe disability. Articular cartilage being unable to repair spontaneously, alterations of the joint surface often results in end-stage osteoarthritis, requiring surgical intervention and total joint replacement. This makes damaged tissues repair a major challenge in our aging society. Cartilage harbors only one cell type, the chondrocyte, which synthesizes and secretes specific matrix proteins such as type II collagen and high molecular weight proteoglycans. Matrix proteins are responsible for the conservation of the chondrocyte phenotype and the maintenance of the mechanical functions of cartilage. Development of therapeutic strategies for cartilage repair should thus comprise not only the replacement of lost cartilage cells but also that of extracellular matrix with cartilage-like properties. Different protocols are under investigation. The most commonly employed materials include transplantation of autologous osteochondral tissue. More recently, cell-based therapies using autologous mature chondrocytes or pre-chondrogenic stem cells have drawn particular attention. Tissue-engineering procedures represent the actual trend in cartilage repair. This approach combines biodegradable polymeric three-dimensional matrixes and isolated prechondrogenic stem cells. The cells are seeded within the biocompatible matrix and then implanted into the joint. Numerous non-degradable and degradable polymers, which efficiently "mimic" the natural surroundings of cartilage cells, are currently under investigation.

  19. A portable, integrated analyzer for microfluidic - based molecular analysis.

    PubMed

    Qiu, Xianbo; Chen, Dafeng; Liu, Changchun; Mauk, Michael G; Kientz, Terry; Bau, Haim H

    2011-10-01

    A portable, fully automated analyzer that provides actuation and flow control to a disposable, self-contained, microfluidic cassette ("chip") for point-of-care, molecular testing is described. The analyzer provides mechanical actuation to compress pouches that pump liquids in the cassette, to open and close diaphragm valves for flow control, and to induce vibrations that enhance stirring. The analyzer also provides thermal actuation for the temperature cycling needed for polymerase chain reaction (PCR) amplification of nucleic acids and for various drying processes. To improve the temperature uniformity of the PCR chamber, the system utilizes a double-sided heating/cooling scheme with a custom feedforward, variable, structural proportional-integral-derivative (FVSPID) controller. The analyzer includes a programmable central processing unit that directs the sequence and timing of the various operations and that is interfaced with a computer. The disposable cassette receives a sample, and it carries out cell lysis, nucleic acid isolation, concentration, and purification, thermal cycling, and either real time or lateral flow (LF) based detection. The system's operation was demonstrated by processing saliva samples spiked with B. cereus cells. The amplicons were detected with a lateral flow assay using upconverting phosphor reporter particles. This system is particularly suited for use in regions lacking centralized laboratory facilities and skilled personnel.

  20. Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

    NASA Technical Reports Server (NTRS)

    Macelroy, R. D.; Pohorille, A.

    1986-01-01

    The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

  1. Construction of an Interspecific Genetic Map Based on InDel and SSR for Mapping the QTLs Affecting the Initiation of Flower Primordia in Pepper (Capsicum spp.)

    PubMed Central

    Qin, Cheng; Nong, Ding-Guo; Li, Wei-Peng; Tang, Xin; Wu, Zhi-Ming; Hu, Kai-Lin

    2015-01-01

    Re-sequencing permits the mining of genome-wide variations on a large scale and provides excellent resources for the research community. To accelerate the development and application of molecular markers and identify the QTLs affecting the flowering time-related trait in pepper, a total of 1,038 pairs of InDel and 674 SSR primers from different sources were used for genetic mapping using the F2 population (n = 154) derived from a cross between BA3 (C. annuum) and YNXML (C. frutescens). Of these, a total of 224 simple PCR-based markers, including 129 InDels and 95 SSRs, were validated and integrated into a map, which was designated as the BY map. The BY map consisted of 13 linkage groups (LGs) and spanned a total genetic distance of 1,249.77 cM with an average marker distance of 5.60 cM. Comparative analysis of the genetic and physical map based on the anchored markers showed that the BY map covered nearly the whole pepper genome. Based on the BY map, one major and five minor QTLs affecting the number of leaves on the primary axis (Nle) were detected on chromosomes P2, P7, P10 and P11 in 2012. The major QTL on P2 was confirmed based on another subset of the same F2 population (n = 147) in 2014 with selective genotyping of markers from the BY map. With the accomplishment of pepper whole genome sequencing and annotations (release 2.0), 153 candidate genes were predicted to embed in the Nle2.2 region, of which 12 important flowering related genes were obtained. The InDel/SSR-based interspecific genetic map, QTLs and candidate genes obtained by the present study will be useful for the downstream isolation of flowering time-related gene and other genetic applications for pepper. PMID:25781878

  2. Construction of an interspecific genetic map based on InDel and SSR for mapping the QTLs affecting the initiation of flower primordia in pepper (Capsicum spp.).

    PubMed

    Tan, Shu; Cheng, Jiao-Wen; Zhang, Li; Qin, Cheng; Nong, Ding-Guo; Li, Wei-Peng; Tang, Xin; Wu, Zhi-Ming; Hu, Kai-Lin

    2015-01-01

    Re-sequencing permits the mining of genome-wide variations on a large scale and provides excellent resources for the research community. To accelerate the development and application of molecular markers and identify the QTLs affecting the flowering time-related trait in pepper, a total of 1,038 pairs of InDel and 674 SSR primers from different sources were used for genetic mapping using the F2 population (n = 154) derived from a cross between BA3 (C. annuum) and YNXML (C. frutescens). Of these, a total of 224 simple PCR-based markers, including 129 InDels and 95 SSRs, were validated and integrated into a map, which was designated as the BY map. The BY map consisted of 13 linkage groups (LGs) and spanned a total genetic distance of 1,249.77 cM with an average marker distance of 5.60 cM. Comparative analysis of the genetic and physical map based on the anchored markers showed that the BY map covered nearly the whole pepper genome. Based on the BY map, one major and five minor QTLs affecting the number of leaves on the primary axis (Nle) were detected on chromosomes P2, P7, P10 and P11 in 2012. The major QTL on P2 was confirmed based on another subset of the same F2 population (n = 147) in 2014 with selective genotyping of markers from the BY map. With the accomplishment of pepper whole genome sequencing and annotations (release 2.0), 153 candidate genes were predicted to embed in the Nle2.2 region, of which 12 important flowering related genes were obtained. The InDel/SSR-based interspecific genetic map, QTLs and candidate genes obtained by the present study will be useful for the downstream isolation of flowering time-related gene and other genetic applications for pepper.

  3. Recent advances in molecular recognition based on nanoengineered platforms.

    PubMed

    Mu, Bin; Zhang, Jingqing; McNicholas, Thomas P; Reuel, Nigel F; Kruss, Sebastian; Strano, Michael S

    2014-04-15

    they are able to obtain loading curves similar to surface plasmon resonance measurements. They demonstrate the sensitivity and specificity of this platform with two higher-affined glycan-lectin pairs: fucose (Fuc) to PA-IIL and N-acetylglucosamine (GlcNAc) to GafD. Lastly, we discuss how developments in protein biomarker detection in general are benefiting specifically from label-free molecular recognition. Electrical field effect transistors, chemi-resistive and fluorometric nanosensors based on various nanomaterials have demonstrated substantial progress in recent years in addressing this challenging problem. In this Account, we compare the balance between sensitivity, selectivity, and nonspecific adsorption for various applications. In particular, our group has utilized SWNTs as fluorescence sensors for label-free protein-protein interaction measurements. In this assay, we have encapsulated each nanotube in a biocompatible polymer, chitosan, which has been further modified to conjugate nitrilotriacetic acid (NTA) groups. After Ni(2+) chelation, NTA Ni(2+) complexes bind to his-tagged proteins, resulting in a local environment change of the SWNT array, leading to optical fluorescence modulation with detection limit down to 100 nM. We have further engineered the platform to monitor single protein binding events, with an even lower detection limit down to 10 pM.

  4. Development of InDel markers for Brassica rapa based on whole-genome re-sequencing.

    PubMed

    Liu, Bo; Wang, Yan; Zhai, Wen; Deng, Jie; Wang, Hui; Cui, Yang; Cheng, Feng; Wang, Xiaowu; Wu, Jian

    2013-01-01

    Genome-wide detection of short insertion/deletion length polymorphisms (InDels, <5 bp) in Brassica rapa (named the A genome) was performed by comparing whole-genome re-sequencing data from two B. rapa accessions, L144 and Z16, to the reference genome sequence of Chiifu-401-42. In total, we identified 108,558 InDel polymorphisms between Chiifu-401-42 and L144, 26,795 InDels between Z16 and Chiifu-401-42, and 26,693 InDels between L144 and Z16. From these, 639 InDel polymorphisms of 3-5 bp in length between L144 and Z16 were selected for experimental validation; 491 (77%) yielded single PCR fragments and showed polymorphisms, 7 (1%) did not amplify a product, and 141 (22%) showed no polymorphism. For further validation of these intra-specific InDel polymorphisms, 503 candidates, randomly selected from the 639 InDels, were screened across seven accessions representing different B. rapa cultivar groups. Of these assayed markers, 387 (77%) were polymorphic, 111 (22%) were not polymorphic and 5 (1%) did not amplify a PCR product. Furthermore, we randomly selected 518 InDel markers to validate their polymorphism in B. napus (the AC genome) and B. juncea (the AB genome), of which more than 90% amplified a PCR product; 132 (25%) showed polymorphism between the two B. napus accessions and 41 (8%) between the two B. juncea accessions. This set of novel PCR-based InDel markers will be a valuable resource for genetic studies and breeding programs in B. rapa.

  5. Development of InDel markers for Brassica rapa based on whole-genome re-sequencing.

    PubMed

    Liu, Bo; Wang, Yan; Zhai, Wen; Deng, Jie; Wang, Hui; Cui, Yang; Cheng, Feng; Wang, Xiaowu; Wu, Jian

    2013-01-01

    Genome-wide detection of short insertion/deletion length polymorphisms (InDels, <5 bp) in Brassica rapa (named the A genome) was performed by comparing whole-genome re-sequencing data from two B. rapa accessions, L144 and Z16, to the reference genome sequence of Chiifu-401-42. In total, we identified 108,558 InDel polymorphisms between Chiifu-401-42 and L144, 26,795 InDels between Z16 and Chiifu-401-42, and 26,693 InDels between L144 and Z16. From these, 639 InDel polymorphisms of 3-5 bp in length between L144 and Z16 were selected for experimental validation; 491 (77%) yielded single PCR fragments and showed polymorphisms, 7 (1%) did not amplify a product, and 141 (22%) showed no polymorphism. For further validation of these intra-specific InDel polymorphisms, 503 candidates, randomly selected from the 639 InDels, were screened across seven accessions representing different B. rapa cultivar groups. Of these assayed markers, 387 (77%) were polymorphic, 111 (22%) were not polymorphic and 5 (1%) did not amplify a PCR product. Furthermore, we randomly selected 518 InDel markers to validate their polymorphism in B. napus (the AC genome) and B. juncea (the AB genome), of which more than 90% amplified a PCR product; 132 (25%) showed polymorphism between the two B. napus accessions and 41 (8%) between the two B. juncea accessions. This set of novel PCR-based InDel markers will be a valuable resource for genetic studies and breeding programs in B. rapa. PMID:22972202

  6. Arrays of high quality SAM-based junctions and their application in molecular diode based logic

    NASA Astrophysics Data System (ADS)

    Wan, Albert; Suchand Sangeeth, C. S.; Wang, Lejia; Yuan, Li; Jiang, Li; Nijhuis, Christian A.

    2015-11-01

    This paper describes a method to fabricate a microfluidic top-electrode that can be utilized to generate arrays of self-assembled monolayer (SAM)-based junctions. The top-electrodes consist of a liquid-metal of GaOx/EGaIn mechanically stabilized in microchannels and through-holes in polydimethylsiloxane (PDMS); these top-electrodes form molecular junctions by directly placing them onto the SAM supported by template-stripped (TS) Ag or Au bottom-electrodes. Unlike conventional techniques to form multiple junctions, our method does not require lithography to pattern the bottom-electrode and is compatible with TS bottom-electrodes, which are ultra-flat with large grains, free from potential contamination of photoresist residues, and do not have electrode-edges where the molecules are unable to pack well. We formed tunneling junctions with n-alkanethiolate SAMs in yields of ~80%, with good reproducibility and electrical stability. Temperature dependent J(V) measurements indicated that the mechanism of charge transport across the junction is coherent tunneling. To demonstrate the usefulness of these junctions, we formed molecular diodes based on SAMs with Fc head groups. These junctions rectify currents with a rectification ratio R of 45. These molecular diodes were incorporated in simple electronic circuitry to demonstrate molecular diode-based Boolean logic.This paper describes a method to fabricate a microfluidic top-electrode that can be utilized to generate arrays of self-assembled monolayer (SAM)-based junctions. The top-electrodes consist of a liquid-metal of GaOx/EGaIn mechanically stabilized in microchannels and through-holes in polydimethylsiloxane (PDMS); these top-electrodes form molecular junctions by directly placing them onto the SAM supported by template-stripped (TS) Ag or Au bottom-electrodes. Unlike conventional techniques to form multiple junctions, our method does not require lithography to pattern the bottom-electrode and is compatible with TS

  7. Fluorescence molecular tomographic image reconstruction based on reduced measurement data

    NASA Astrophysics Data System (ADS)

    Zou, Wei; Wang, Jiajun; Feng, David Dagan; Fang, Erxi

    2015-07-01

    The analysis of fluorescence molecular tomography is important for medical diagnosis and treatment. Although the quality of reconstructed results can be improved with the increasing number of measurement data, the scale of the matrices involved in the reconstruction of fluorescence molecular tomography will also become larger, which may slow down the reconstruction process. A new method is proposed where measurement data are reduced according to the rows of the Jacobian matrix and the projection residual error. To further accelerate the reconstruction process, the global inverse problem is solved with level-by-level Schur complement decomposition. Simulation results demonstrate that the speed of the reconstruction process can be improved with the proposed algorithm.

  8. Photocatalytic water oxidation by molecular assemblies based on cobalt catalysts.

    PubMed

    Zhou, Xu; Li, Fei; Li, Hua; Zhang, Biaobiao; Yu, Fengshou; Sun, Licheng

    2014-09-01

    Chromophore-catalyst molecular assemblies towards visible light-driven water oxidation were synthesized by covalent integration of a light-harvesting complex [Ru(bpy)3](2+) (bpy=2,2'-bipyridine) and a Co4O4 cubane water oxidation catalyst. The two components were assembled either in linear or macrocyclic configurations. In the presence of the sacrificial reagent, the Ru-Co metallocycle exhibits remarkable photocatalytic activity for oxygen evolution, which is one order of magnitude higher than that of a multicomponent system and exceeds that of a linear assembly by a factor of five, offering access to highly active photocatalyst through molecular design. PMID:25111070

  9. Sugar-based molecular computing by material implication.

    PubMed

    Elstner, Martin; Axthelm, Jörg; Schiller, Alexander

    2014-07-01

    A method to integrate an (in principle) unlimited number of molecular logic gates to construct complex circuits is presented. Logic circuits, such as half- or full-adders, can be reinterpreted by using the functional completeness of the implication function (IMP) and the trivial FALSE operation. The molecular gate IMP is represented by a fluorescent boronic acid sugar probe. An external wiring algorithm translates the fluorescent output from one gate into a chemical input for the next gate on microtiter plates. This process is demonstrated on a four-bit full adder. PMID:24924187

  10. Congenital neutropenia: diagnosis, molecular bases and patient management

    PubMed Central

    2011-01-01

    The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l. When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte

  11. Engineering controllable bidirectional molecular motors based on myosin

    NASA Astrophysics Data System (ADS)

    Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

    2012-04-01

    Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

  12. An Inquiry-based Introduction to Molecular Biology.

    ERIC Educational Resources Information Center

    Levy, Foster

    2000-01-01

    Presents investigative approaches to teaching molecular biology. Emphasizes a deductive determination of the nature of nucleic acids visualized in a gel, and a comparison of different genomes. Asks why students should take it on faith that what they view on a gel is DNA. (SAH)

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

    ERIC Educational Resources Information Center

    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…

  14. Genetic diversity and population structure in Physalis peruviana and related taxa based on InDels and SNPs derived from COSII and IRG markers

    PubMed Central

    Garzón-Martínez, Gina A.; Osorio-Guarín, Jaime A.; Delgadillo-Durán, Paola; Mayorga, Franklin; Enciso-Rodríguez, Felix E.; Landsman, David

    2015-01-01

    The genus Physalis is common in the Americas and includes several economically important species, among them Physalis peruviana that produces appetizing edible fruits. We studied the genetic diversity and population structure of P. peruviana and characterized 47 accessions of this species along with 13 accessions of related taxa consisting of 222 individuals from the Colombian Corporation of Agricultural Research (CORPOICA) germplasm collection, using Conserved Orthologous Sequences (COSII) and Immunity Related Genes (IRGs). In addition, 642 Single Nucleotide Polymorphism (SNPs) markers were identified and used for the genetic diversity analysis. A total of 121 alleles were detected in 24 InDels loci ranging from 2 to 9 alleles per locus, with an average of 5.04 alleles per locus. The average number of alleles in the SNP markers was two. The observed heterozygosity for P. peruviana with InDel and SNP markers was higher (0.48 and 0.59) than the expected heterozygosity (0.30 and 0.41). Interestingly, the observed heterozygosity in related taxa (0.4 and 0.12) was lower than the expected heterozygosity (0.59 and 0.25). The coefficient of population differentiation FST was 0.143 (InDels) and 0.038 (SNPs), showing a relatively low level of genetic differentiation among P. peruviana and related taxa. Higher levels of genetic variation were instead observed within populations based on the AMOVA analysis. Population structure analysis supported the presence of two main groups and PCA analysis based on SNP markers revealed two distinct clusters in the P. peruviana accessions corresponding to their state of cultivation. In this study, we identified molecular markers useful to detect genetic variation in Physalis germplasm for assisting conservation and crossbreeding strategies. PMID:26550601

  15. Effect of molecular electrical doping on polyfuran based photovoltaic cells

    SciTech Connect

    Yu, Shuwen; Opitz, Andreas; Salzmann, Ingo; Frisch, Johannes; Cohen, Erez; Bendikov, Michael; Koch, Norbert

    2015-05-18

    The electronic, optical, and morphological properties of molecularly p-doped polyfuran (PF) films were investigated over a wide range of doping ratio in order to explore the impact of doping in photovoltaic applications. We find evidence for integer-charge transfer between PF and the prototypical molecular p-dopant tetrafluoro-tetracyanoquinodimethane (F4TCNQ) and employed the doped polymer in bilayer organic solar cells using fullerene as acceptor. The conductivity increase in the PF films at dopant loadings ≤2% significantly enhances the short-circuit current of photovoltaic devices. For higher doping ratios, however, F4TCNQ is found to precipitate at the heterojunction between the doped donor polymer and the fullerene acceptor. Ultraviolet photoelectron spectroscopy reveals that its presence acts beneficial to the energy-level alignment by doubling the open-circuit voltage of solar cells from 0.2 V to ca. 0.4 V, as compared to pristine PF.

  16. Deciphering the molecular bases for drought tolerance in Arabidopsis autotetraploids.

    PubMed

    del Pozo, Juan C; Ramirez-Parra, Elena

    2014-12-01

    Whole genome duplication (autopolyploidy) is common in many plant species and often leads to better adaptation to adverse environmental conditions. However, little is known about the physiological and molecular mechanisms underlying these adaptations. Drought is one of the major environmental conditions limiting plant growth and development. Here, we report that, in Arabidopsis thaliana, tetraploidy promotes alterations in cell proliferation and organ size in a tissue-dependent manner. Furthermore, it potentiates plant tolerance to salt and drought stresses and decreases transpiration rate, likely through controlling stomata density and closure, abscisic acid (ABA) signalling and reactive oxygen species (ROS) homeostasis. Our transcriptomic analyses revealed that tetraploidy mainly regulates the expression of genes involved in redox homeostasis and ABA and stress response. Taken together, our data have shed light on the molecular basis associated with stress tolerance in autopolyploid plants.

  17. Effect of molecular electrical doping on polyfuran based photovoltaic cells

    NASA Astrophysics Data System (ADS)

    Yu, Shuwen; Frisch, Johannes; Opitz, Andreas; Cohen, Erez; Bendikov, Michael; Koch, Norbert; Salzmann, Ingo

    2015-05-01

    The electronic, optical, and morphological properties of molecularly p-doped polyfuran (PF) films were investigated over a wide range of doping ratio in order to explore the impact of doping in photovoltaic applications. We find evidence for integer-charge transfer between PF and the prototypical molecular p-dopant tetrafluoro-tetracyanoquinodimethane (F4TCNQ) and employed the doped polymer in bilayer organic solar cells using fullerene as acceptor. The conductivity increase in the PF films at dopant loadings ≤2% significantly enhances the short-circuit current of photovoltaic devices. For higher doping ratios, however, F4TCNQ is found to precipitate at the heterojunction between the doped donor polymer and the fullerene acceptor. Ultraviolet photoelectron spectroscopy reveals that its presence acts beneficial to the energy-level alignment by doubling the open-circuit voltage of solar cells from 0.2 V to ca. 0.4 V, as compared to pristine PF.

  18. The HITRAN molecular data base - Editions of 1991 and 1992

    NASA Technical Reports Server (NTRS)

    Rothman, Laurence S.; Gamache, R. R.; Tipping, R. H.; Rinsland, C. P.; Smith, M. A. H.; Benner, D. C.; Devi, V. M.; Flaud, J.-M.; Camy-Peyret, C.; Perrin, A.

    1992-01-01

    We describe in this paper the modifications, improvements, and enhancements to the HITRAN molecular absorption database that have occurred in the two editions of 1991 and 1992. The current database includes line parameters for 31 species and their isotopomers that are significant for terrestrial atmospheric studies. This line-by-line portion of HITRAN presently contains about 709,000 transitions between 0 and 23,000/cm and contains three molecules not present in earlier versions: COF2, SF6, and H2S. The HITRAN compilation has substantially more information on chlorofluorocarbons and other molecular species that exhibit dense spectra which are not amenable to line-by-line representation. The user access of the database has been advanced, and new media forms are now available for use on personal computers.

  19. [Personalized urooncology based on molecular uropathology: what is the future?].

    PubMed

    Dahl, E; Haller, F

    2013-07-01

    Targeted therapies and biomarker validation are key drivers in the advancement of personalized oncology which is a growing topic in all clinical areas. Compared with other professions, such as pulmonology and gynecology, development in urology has so far been retarded but has recently gained increasing momentum. A basis for this is the currently growing and in future accelerated application of new knowledge derived from molecular biology in the field of uropathology. The rapid gain of knowledge is driven by a whole new class of analytical methods, such as massively parallel sequencing (deep sequencing or next generation sequencing), which enables analysis of virtually a new universe of potential biomarkers. This article describes the emerging paradigm shift in molecular pathological diagnostics of urological tumors using the example of prostate cancer.

  20. Extending the molecular clutch beyond actin-based cell motility

    NASA Astrophysics Data System (ADS)

    Havrylenko, Svitlana; Mezanges, Xavier; Batchelder, Ellen; Plastino, Julie

    2014-10-01

    Many cell movements occur via polymerization of the actin cytoskeleton beneath the plasma membrane at the front of the cell, forming a protrusion called a lamellipodium, while myosin contraction squeezes forward the back of the cell. In what is known as the ‘molecular clutch’ description of cell motility, forward movement results from the engagement of the acto-myosin motor with cell-matrix adhesions, thus transmitting force to the substrate and producing movement. However during cell translocation, clutch engagement is not perfect, and as a result, the cytoskeleton slips with respect to the substrate, undergoing backward (retrograde) flow in the direction of the cell body. Retrograde flow is therefore inversely proportional to cell speed and depends on adhesion and acto-myosin dynamics. Here we asked whether the molecular clutch was a general mechanism by measuring motility and retrograde flow for the Caenorhabditis elegans sperm cell in different adhesive conditions. These cells move by adhering to the substrate and emitting a dynamic lamellipodium, but the sperm cell does not contain an acto-myosin cytoskeleton. Instead the lamellipodium is formed by the assembly of major sperm protein, which has no biochemical or structural similarity to actin. We find that these cells display the same molecular clutch characteristics as acto-myosin containing cells. We further show that retrograde flow is produced both by cytoskeletal assembly and contractility in these cells. Overall this study shows that the molecular clutch hypothesis of how polymerization is transduced into motility via adhesions is a general description of cell movement regardless of the composition of the cytoskeleton.

  1. Extending the molecular clutch beyond actin-based cell motility

    PubMed Central

    Havrylenko, Svitlana; Mezanges, Xavier; Batchelder, Ellen; Plastino, Julie

    2014-01-01

    Many cell movements occur via polymerization of the actin cytoskeleton beneath the plasma membrane at the front of the cell, forming a protrusion called a lamellipodium, while myosin contraction squeezes forward the back of the cell. In what is known as the “molecular clutch” description of cell motility, forward movement results from the engagement of the acto-myosin motor with cell-matrix adhesions, thus transmitting force to the substrate and producing movement. However during cell translocation, clutch engagement is not perfect, and as a result, the cytoskeleton slips with respect to the substrate, undergoing backward (retrograde) flow in the direction of the cell body. Retrograde flow is therefore inversely proportional to cell speed and depends on adhesion and acto-myosin dynamics. Here we asked whether the molecular clutch was a general mechanism by measuring motility and retrograde flow for the Caenorhabditis elegans sperm cell in different adhesive conditions. These cells move by adhering to the substrate and emitting a dynamic lamellipodium, but the sperm cell does not contain an acto-myosin cytoskeleton. Instead the lamellipodium is formed by the assembly of Major Sperm Protein (MSP), which has no biochemical or structural similarity to actin. We find that these cells display the same molecular clutch characteristics as acto-myosin containing cells. We further show that retrograde flow is produced both by cytoskeletal assembly and contractility in these cells. Overall this study shows that the molecular clutch hypothesis of how polymerization is transduced into motility via adhesions is a general description of cell movement regardless of the composition of the cytoskeleton. PMID:25383039

  2. Molecular dynamics simulations of carbon nanotube-based gears

    NASA Astrophysics Data System (ADS)

    Han, Jie; Globus, Al; Jaffe, Richard; Deardorff, Glenn

    1997-09-01

    We use a molecular dynamics simulation to investigate the properties and design space of molecular gears fashioned from carbon nanotubes with teeth added via a benzyne reaction known to occur with 0957-4484/8/3/001/img1. Brenner's reactive hydrocarbon potential is used to model interatomic forces within each molecular gear. A Lennard - Jones 6 - 12 potential or the Buckingham 0957-4484/8/3/001/img2 potential plus electrostatic interaction terms are used for intermolecular interactions between gears. A number of gear and gear/shaft configurations are simulated on parallel computers. One gear is powered by forcing the atoms near the end of the nanotube to rotate, and a second gear is allowed to rotate by keeping the atoms near the end of its nanotube constrained to a cylinder. The meshing aromatic gear teeth transfer angular momentum from the powered gear to the driven gear. Results suggest that these gears can operate at up to 50 - 100 GHz in a vacuum at room temperature. The failure mode involves tooth slip, not bond breaking, so failed gears can be returned to operation by lowering the temperature and/or rotation rate.

  3. Molecular Dynamics Simulation of Carbon Nanotube Based Gears

    NASA Technical Reports Server (NTRS)

    Han, Jie; Globus, Al; Jaffe, Richard; Deardorff, Glenn; Chancellor, Marisa K. (Technical Monitor)

    1996-01-01

    We used molecular dynamics to investigate the properties and design space of molecular gears fashioned from carbon nanotubes with teeth added via a benzyne reaction known to occur with C60. A modified, parallelized version of Brenner's potential was used to model interatomic forces within each molecule. A Leonard-Jones 6-12 potential was used for forces between molecules. One gear was powered by forcing the atoms near the end of the buckytube to rotate, and a second gear was allowed.to rotate by keeping the atoms near the end of its buckytube on a cylinder. The meshing aromatic gear teeth transfer angular momentum from the powered gear to the driven gear. A number of gear and gear/shaft configurations were simulated. Cases in vacuum and with an inert atmosphere were examined. In an extension to molecular dynamics technology, some simulations used a thermostat on the atmosphere while the hydrocarbon gear's temperature was allowed to fluctuate. This models cooling the gears with an atmosphere. Results suggest that these gears can operate at up to 50-100 gigahertz in a vacuum or inert atmosphere at room temperature. The failure mode involves tooth slip, not bond breaking, so failed gears can be returned to operation by lowering temperature and/or rotation rate. Videos and atomic trajectory files in xyz format are presented.

  4. Electronic Transport in Molecular Junction Based on C20 Cages

    NASA Astrophysics Data System (ADS)

    Ouyang, Fang-Ping; Xu, Hui

    2007-04-01

    Choosing closed-ended armchair (5, 5) single-wall carbon nanotubes (CCNTs) as electrodes, we investigate the electron transport properties across an all-carbon molecular junction consisting of C20 molecules suspended between two semi-infinite carbon nanotubes. It is shown that the conductances are quite sensitive to the number of C20 molecules between electrodes for both configuration CF1 and double-bonded models: the conductances of C20 dimers are markedly smaller than those of monomers. The physics is that incident electrons easily pass the C20 molecules and are predominantly scattered at the C20-C20 junctions. Moreover, we study the doping effect of such molecular junction by doping nitrogen atoms substitutionally. The bonding property of the molecular junction with configuration CF1 has been analysed by calculating the Mulliken atomic charges. Our results have revealed that the C atoms in N-doped junctions are more ionic than those in pure-carbon ones, leading to the fact that N-doped junctions have relatively large conductance.

  5. VAMMPIRE: a matched molecular pairs database for structure-based drug design and optimization.

    PubMed

    Weber, Julia; Achenbach, Janosch; Moser, Daniel; Proschak, Ewgenij

    2013-06-27

    Structure-based optimization to improve the affinity of a lead compound is an established approach in drug discovery. Knowledge-based databases holding molecular replacements can be supportive in the optimization process. We introduce a strategy to relate the substitution effect within matched molecular pairs (MMPs) to the atom environment within the cocrystallized protein-ligand complex. Virtually Aligned Matched Molecular Pairs Including Receptor Environment (VAMMPIRE) database and the supplementary web interface ( http://vammpire.pharmchem.uni-frankfurt.de ) provide valuable information for structure-based lead optimization.

  6. The Eyes Have It: A Problem-Based Learning Exercise in Molecular Evolution

    ERIC Educational Resources Information Center

    White, Harold B.

    2007-01-01

    Molecular evolution provides an interesting context in which to use problem-based learning because it integrates a variety of topics in biology, biochemistry, and molecular biology. This three-stage problem for advanced students deals with the structure, multiple functions, and properties of lactate dehydrogenase isozymes, and the related…

  7. Rapid Prototyping of Chemical Microsensors Based on Molecularly Imprinted Polymers Synthesized by Two-Photon Stereolithography.

    PubMed

    Gomez, Laura Piedad Chia; Spangenberg, Arnaud; Ton, Xuan-Anh; Fuchs, Yannick; Bokeloh, Frank; Malval, Jean-Pierre; Tse Sum Bui, Bernadette; Thuau, Damien; Ayela, Cédric; Haupt, Karsten; Soppera, Olivier

    2016-07-01

    Two-photon stereolithography is used for rapid prototyping of submicrometre molecularly imprinted polymer-based 3D structures. The structures are evaluated as chemical sensing elements and their specific recognition properties for target molecules are confirmed. The 3D design capability is exploited and highlighted through the fabrication of an all-organic molecularly imprinted polymeric microelectromechanical sensor.

  8. Rapid Prototyping of Chemical Microsensors Based on Molecularly Imprinted Polymers Synthesized by Two-Photon Stereolithography.

    PubMed

    Gomez, Laura Piedad Chia; Spangenberg, Arnaud; Ton, Xuan-Anh; Fuchs, Yannick; Bokeloh, Frank; Malval, Jean-Pierre; Tse Sum Bui, Bernadette; Thuau, Damien; Ayela, Cédric; Haupt, Karsten; Soppera, Olivier

    2016-07-01

    Two-photon stereolithography is used for rapid prototyping of submicrometre molecularly imprinted polymer-based 3D structures. The structures are evaluated as chemical sensing elements and their specific recognition properties for target molecules are confirmed. The 3D design capability is exploited and highlighted through the fabrication of an all-organic molecularly imprinted polymeric microelectromechanical sensor. PMID:27145145

  9. Molecular recognition of α-cyclodextrin (CD) to choral amino acids based on methyl orange as a molecular probe

    NASA Astrophysics Data System (ADS)

    Yuexian, Fan; Yu, Yang; Shaomin, Shuang; Chuan, Dong

    2005-03-01

    The molecular recognition interaction of α-CD to chiral amino acids was investigated by using spectrophotometry based on methyl orange as a molecular probe. The molecular recognition ability depended on the inclusion formation constants. The molecular recognition of α-CD to aromatic amino acids was the order: DL-tryptophan > L-tryptophan > L-phenylalanine > L-tyrosine ≈ DL-β-3,4-dihydroxy-phenylalanine; whereas for aliphatic amino acids, the order was: L- iso-leucine > L-leucine ≈ L-methionine ≈ DL-mehtionine > D-leucine. The effect of temperature on the inclusion interaction was examined and the thermodynamic parameters of inclusion process, Δ G, Δ H, Δ S, were determined. The experimental results indicated that the inclusion process was an exothermic and enthalpy-driven process accompanied with a negative or minor positive entropic contribution. The inclusion interaction between α-CD and amino acids satisfied the law of enthalpy-entropy compensation. The compensation temperature was 291 K.

  10. Drug repositioning by kernel-based integration of molecular structure, molecular activity, and phenotype data.

    PubMed

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems.

  11. Quantitative analysis of localized surface plasmons based on molecular probing.

    PubMed

    Deeb, Claire; Bachelot, Renaud; Plain, Jérôme; Baudrion, Anne-Laure; Jradi, Safi; Bouhelier, Alexandre; Soppera, Olivier; Jain, Prashant K; Huang, Libai; Ecoffet, Carole; Balan, Lavinia; Royer, Pascal

    2010-08-24

    We report on the quantitative characterization of the plasmonic optical near-field of a single silver nanoparticle. Our approach relies on nanoscale molecular molding of the confined electromagnetic field by photoactivated molecules. We were able to directly image the dipolar profile of the near-field distribution with a resolution better than 10 nm and to quantify the near-field depth and its enhancement factor. A single nanoparticle spectral signature was also assessed. This quantitative characterization constitutes a prerequisite for developing nanophotonic applications.

  12. Vibrational Spectra of Molecular Crystals with the Generalized Energy-Based Fragmentation Approach.

    PubMed

    Fang, Tao; Jia, Junteng; Li, Shuhua

    2016-05-01

    The generalized energy-based fragmentation (GEBF) approach for molecular crystals with periodic boundary condition (PBC) (denoted as PBC-GEBF) is extended to allow vibrational spectra of molecular crystals to be easily computed at various theory levels. Within the PBC-GEBF approach, the vibrational frequencies of a molecular crystal can be directly evaluated from molecular quantum chemistry calculations on a series of nonperiodic molecular systems. With this approach, the vibrational spectra of molecular crystals can be calculated with much reduced computational costs at various theory levels, as compared to those required by the methods based on periodic electronic structure theory. By testing the performance of the PBC-GEBF method for two molecular crystals (CO2 and imidazole), we demonstrate that the PBC-GEBF approach can reproduce the results of the methods based on periodic electronic structure theory in predicting vibrational spectra of molecular crystals. We apply the PBC-GEBF method at second-order Møller-Plesset perturbation theory (PBC-GEBF-MP2 in short) to investigate the vibrational spectra of the urea and ammonia borane crystals. Our results show that the PBC-GEBF-MP2 method can provide quite accurate descriptions for the observed vibrational spectra of the two systems under study.

  13. A graphene oxide (GO)-based molecular beacon for DNA-binding transcription factor detection.

    PubMed

    Liu, Jing-Jing; Song, Xiao-Rong; Wang, Yi-Wei; Chen, Guo-Nan; Yang, Huang-Hao

    2012-06-21

    A GO-based molecular beacon assay was developed for rapid, sensitive and cost-efficient detection of transcription factor proteins. Furthermore, this assay can be employed for screening inhibitors of transcription factor proteins.

  14. A room-temperature adenosine-based molecular beacon for highly sensitive detection of nucleic acids.

    PubMed

    Lin, Yen-Hsiu; Tseng, Wei-Lung

    2012-06-25

    This study developed a simple, sensitive, and selective molecular beacon for detecting nucleic acids at room temperature based on coralyne induced conformational change of a MB through A(2)-coralyne-A(2) coordination.

  15. Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

    SciTech Connect

    Rajagopalan, Raghavan

    2006-01-30

    The overall objective of the SBIR Phase I proposal is to prepare and evaluate a new class of {sup 99m}Tc or {sup 94m}Tc containing estrogen-like small molecules ('estrogen mimics') for SPECT or PET molecular imaging of estrogen receptor positive (ER+) tumors. In this approach, the metal ion is integrated into the estrone skeleton by isosteric substitution of a carbon atom in the steroidal structure to give new class of mimics that are topologically similar to the native estrogen (Fig. 1). Although both N{sub 2}S{sub 2} and N{sub 3}S mimics 1 and 2 were considered as target structures, molecular modeling study revealed that the presence of the acetyl group at position-15 in the N{sub 3}S mimic 2 causes steric hinderance toward binding of 2 to SHBG. Therefore, initial efforts were directed at the synthesis and evaluation of the N{sub 2}S{sub 2} mimic 1.

  16. Choline metabolism-based molecular diagnosis of cancer: an update

    PubMed Central

    Glunde, Kristine; Penet, Marie-France; Jiang, Lu; Jacobs, Michael A; Bhujwalla, Zaver M

    2016-01-01

    Abnormal choline metabolism continues to be identified in multiple cancers. Molecular causes of abnormal choline metabolism are changes in choline kinase-α, ethanolamine kinase-α, phosphatidylcholine-specific phospholipase C and -D and glycerophosphocholine phosphodiesterases, as well as several choline transporters. The net outcome of these enzymatic changes is an increase in phosphocholine and total choline (tCho) and, in some cancers, a relative decrease of glycerophosphocholine. The increased tCho signal detected by 1H magnetic resonance spectroscopy is being evaluated as a diagnostic marker in multiple cancers. Increased expression and activity of choline transporters and choline kinase-α have spurred the development of radiolabeled choline analogs as PET imaging tracers. Both tCho 1H magnetic resonance spectroscopy and choline PET are being investigated to detect response to treatment. Enzymes mediating the abnormal choline metabolism are being explored as targets for cancer therapy. This review highlights recent molecular, therapeutic and clinical advances in choline metabolism in cancer. PMID:25921026

  17. Linking traits based on their shared molecular mechanisms

    PubMed Central

    Oren, Yael; Nachshon, Aharon; Frishberg, Amit; Wilentzik, Roni; Gat-Viks, Irit

    2015-01-01

    There is growing recognition that co-morbidity and co-occurrence of disease traits are often determined by shared genetic and molecular mechanisms. In most cases, however, the specific mechanisms that lead to such trait–trait relationships are yet unknown. Here we present an analysis of a broad spectrum of behavioral and physiological traits together with gene-expression measurements across genetically diverse mouse strains. We develop an unbiased methodology that constructs potentially overlapping groups of traits and resolves their underlying combination of genetic loci and molecular mechanisms. For example, our method predicts that genetic variation in the Klf7 gene may influence gene transcripts in bone marrow-derived myeloid cells, which in turn affect 17 behavioral traits following morphine injection; this predicted effect of Klf7 is consistent with an in vitro perturbation of Klf7 in bone marrow cells. Our analysis demonstrates the utility of studying hidden causative mechanisms that lead to relationships between complex traits. DOI: http://dx.doi.org/10.7554/eLife.04346.001 PMID:25781485

  18. Fishing the molecular bases of Treacher Collins syndrome.

    PubMed

    Weiner, Andrea M J; Scampoli, Nadia L; Calcaterra, Nora B

    2012-01-01

    Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

  19. Fishing the Molecular Bases of Treacher Collins Syndrome

    PubMed Central

    Weiner, Andrea M. J.; Scampoli, Nadia L.; Calcaterra, Nora B.

    2012-01-01

    Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development. PMID:22295061

  20. Quantum-dots-encoded-microbeads based molecularly imprinted polymer.

    PubMed

    Liu, Yixi; Liu, Le; He, Yonghong; He, Qinghua; Ma, Hui

    2016-03-15

    Quantum dots encoded microbeads have various advantages such as large surface area, superb optical properties and the ability of multiplexing. Molecularly imprinted polymer that can mimic the natural recognition entities has high affinity and selectivity for the specific analyte. Here, the concept of utilizing the quantum dots encoded microbeads as the supporting material and the polydopamine as the functional monomer to form the core-shell molecular imprinted polymer was proposed for the first time. The resulted imprinted polymer can provide various merits: polymerization can complete in aqueous environment; fabrication procedure is facile and universal; the obvious economic advantage; the thickness of the imprinting layer is highly controllable; polydopamine coating can improve the biocompatibility of the quantum dot encoded microbeads. The rabbit IgG binding and flow cytometer experiment result showed the distinct advantages of this strategy: cost-saving, facile and fast preparation procedure. Most importantly, the ability for the multichannel detection, which makes the imprinted polydopamine modified encoded-beads very attractive in protein pre-concentration, recognition, separation and biosensing. PMID:26520251

  1. [Molecular bases of cellular senescence: Hayflick phenomenon 50 years later].

    PubMed

    Sosińska, Patrycja; Mikuła-Pietrasik, Justyna; Książek, Krzysztof

    2016-03-17

    Normal human somatic cells have strictly limited proliferative capacity and reach a state of senescence when it becomes exhausted. It is believed that senescence is a response to extensive and irreparable DNA injury, localized in telomeric and/or non-telomeric regions of the genome. Main cause of this damage is oxidative stress, increasing due to deteriorated function of mitochondria. Senescent cells accumulate in tissues during aging, which is causatively linked with the development of various pathologies in elderly individuals, including cancer. This paper, prepared exactly 50 years after Leonard Hayflick's discovery of the relationship between cellular senescence and organismal aging is aimed at presenting the current knowledge about molecular determinants of senescence, with particular emphasis paid to the role of oxidative stress, effectors of senescence at the level of cell cycle, markers of this phenomenon, and the effect of senescent cells on the development of certain age-related diseases.

  2. Two Molecular Information Processing Systems Based on Catalytic Nucleic Acids

    NASA Astrophysics Data System (ADS)

    Stojanovic, Milan

    Mixtures of molecules are capable of powerful information processing [1]. This statement is in the following way self-evident: it is a hierarchically organized complex mixture of molecules that is formulating it to other similarly organized mixtures of molecules. By making such a statement I am not endorsing the extreme forms of reductionism; rather, I am making what I think is a small first step towards harnessing information processing prowess of molecules and, hopefully, overcoming some limitations of more traditional computing paradigms. There are different ideas on how to understand and use molecular information processing abilities and I will list some below. My list is far from inclusive, and delineations are far from clear-cut; whenever available, I will provide examples from our research efforts. I should stress, for a computer science audience that I am a chemist. Thus, my approach may have much different focus and mathematical rigor, then if it would be taken by a computer scientist.

  3. Synopsis of Trichosanthes (Cucurbitaceae) based on recent molecular phylogenetic data

    PubMed Central

    de Boer, Hugo J.; Thulin, Mats

    2012-01-01

    Abstract The snake gourd genus, Trichosanthes, is the largest genus in the Cucurbitaceae family, with over 90 species. Recent molecular phylogenetic data have indicated that the genus Gymnopetalum is to be merged with Trichosanthes to maintain monophyly. A revised infrageneric classification of Trichosanthes including Gymnopetalum is proposed with two subgenera, (I) subg. Scotanthus comb. nov. and (II) subg. Trichosanthes, eleven sections, (i) sect. Asterospermae, (ii) sect. Cucumeroides, (iii) sect. Edulis, (iv) sect. Foliobracteola, (v) sect. Gymnopetalum, (vi) sect. Involucraria, (vii) sect. Pseudovariifera sect. nov., (viii) sect. Villosae stat. nov., (ix) sect. Trichosanthes, (x) sect. Tripodanthera, and (xi) sect. Truncata. A synopsis of Trichosanthes with the 91 species recognized here is presented, including four new combinations, Trichosanthes orientalis, Trichosanthes tubiflora, Trichosanthes scabra var. pectinata, Trichosanthes scabra var. penicaudii, and a clarified nomenclature of Trichosanthes costata and Trichosanthes scabra. PMID:22645411

  4. [Molecular bases of cellular senescence: Hayflick phenomenon 50 years later].

    PubMed

    Sosińska, Patrycja; Mikuła-Pietrasik, Justyna; Książek, Krzysztof

    2016-01-01

    Normal human somatic cells have strictly limited proliferative capacity and reach a state of senescence when it becomes exhausted. It is believed that senescence is a response to extensive and irreparable DNA injury, localized in telomeric and/or non-telomeric regions of the genome. Main cause of this damage is oxidative stress, increasing due to deteriorated function of mitochondria. Senescent cells accumulate in tissues during aging, which is causatively linked with the development of various pathologies in elderly individuals, including cancer. This paper, prepared exactly 50 years after Leonard Hayflick's discovery of the relationship between cellular senescence and organismal aging is aimed at presenting the current knowledge about molecular determinants of senescence, with particular emphasis paid to the role of oxidative stress, effectors of senescence at the level of cell cycle, markers of this phenomenon, and the effect of senescent cells on the development of certain age-related diseases. PMID:27117098

  5. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity

    PubMed Central

    Alsamarah, Abdelaziz; LaCuran, Alecander E.; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

    2015-01-01

    Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

  6. Genetic diversity analysis of common beans based on molecular markers

    PubMed Central

    Gill-Langarica, Homar R.; Muruaga-Martínez, José S.; Vargas-Vázquez, M.L. Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-01-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation. PMID:22215964

  7. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity.

    PubMed

    Alsamarah, Abdelaziz; LaCuran, Alecander E; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

    2015-01-01

    Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

  8. Genetic diversity analysis of common beans based on molecular markers.

    PubMed

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-10-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  9. A molecular beacon-based method for screening cervical cancer.

    PubMed

    Han, Suxia; Li, Ling; Jia, Xi; Ou, Wei; Ma, Jinlu; Wang, Hao; Zhao, Jing; Zhu, Qing

    2012-11-01

    The aim of this study is to develop a new screening method, molecular beacon (MB) imaging, for detection of cervical cancer and to determine its potential clinical applications by examining the sensitivity and specificity of target-specific MBs. Two target-specific molecular beacons were designed and synthesized for survivin and HPV16E6 mRNA. The two designed MBs and a random control MB were used to detect cervical cancer cell lines and a normal cell line. RT-PCR and western blot targeting survivin and HPV16E6 was done for verification. Furthermore the sensitivity and the specificity of the survivin and HPV16E6 mRNA MBs were examined in smears from 125 clinical cervical patients. The survivin and HPV16E6 mRNA MBs generated a strong fluorescence signal in cervical cancer cell lines, but not in the normal cell line, while the random control MB did not generated any signal in both cell lines. The fluorescence intensity correlated well with the gene expression levels in the cells determined by reverse transcription-PCR and Western blot analysis. The clinical sensitivity and the specificity of survivin MB-FITC were 72.5 and 77% while those of HPV16E6 MB-Cy3 were 96.1% and 71.6%, respectively. A parallel test of the two target MBs showed that the sensitivity increased to 98% and the specificity was 70.2%. The survivin and HPV16E6 mRNA MBs showed good reliability and sensitivity. They have great potential for clinical use in cervical cancer screening.

  10. Highly efficient and exact method for parallelization of grid-based algorithms and its implementation in DelPhi

    PubMed Central

    Li, Chuan; Li, Lin; Zhang, Jie; Alexov, Emil

    2012-01-01

    The Gauss-Seidel method is a standard iterative numerical method widely used to solve a system of equations and, in general, is more efficient comparing to other iterative methods, such as the Jacobi method. However, standard implementation of the Gauss-Seidel method restricts its utilization in parallel computing due to its requirement of using updated neighboring values (i.e., in current iteration) as soon as they are available. Here we report an efficient and exact (not requiring assumptions) method to parallelize iterations and to reduce the computational time as a linear/nearly linear function of the number of CPUs. In contrast to other existing solutions, our method does not require any assumptions and is equally applicable for solving linear and nonlinear equations. This approach is implemented in the DelPhi program, which is a finite difference Poisson-Boltzmann equation solver to model electrostatics in molecular biology. This development makes the iterative procedure on obtaining the electrostatic potential distribution in the parallelized DelPhi several folds faster than that in the serial code. Further we demonstrate the advantages of the new parallelized DelPhi by computing the electrostatic potential and the corresponding energies of large supramolecular structures. PMID:22674480

  11. Fragment based G-QSAR and molecular dynamics based mechanistic simulations into hydroxamic-based HDAC inhibitors against spinocerebellar ataxia.

    PubMed

    Sinha, Siddharth; Tyagi, Chetna; Goyal, Sukriti; Jamal, Salma; Somvanshi, Pallavi; Grover, Abhinav

    2016-10-01

    Expansion of polyglutamine (CAG) triplets within the coding gene ataxin 2 results in transcriptional repression, forming the molecular basis of the neurodegenerative disorder named spinocerebellar ataxia type-2 (SCA2). HDAC inhibitors (HDACi) have been elements of great interest in polyglutamine disorders such as Huntington's and Ataxia's. In this study, we have selected hydroxamic acid derivatives as HDACi and performed fragment-based G-QSAR, molecular docking studies and molecular dynamics simulations for elucidating the dynamic mode of action of HDACi with His-Asp catalytic dyad of HDAC4. The model was statistically validated to establish its predictive robustness. The model was statistically significant with r(2) value of .6297, cross-validated co-relation coefficient q(2) value of .5905 and pred_r(2) (predicted square co-relation coefficient) value of .85. An F-test value of 56.11 confirms absolute robustness of the model. Two combinatorial libraries comprising of 3180 compounds were created with hydroxamate moiety as the template and their pIC50 activities were predicted based on the G-QSAR model. The combinatorial library created was screened on the basis of predicted activity (pIC50), with two resultant top scoring compounds, HIC and DHC. The interaction of the compounds with His-Asp dyad in terms of H-bond interactions with His802, Asp840, Pro942, and Gly975 residues of HDAC4 was evaluated by docking and 20 ns long molecular dynamics simulations. This study provides valuable leads for structural substitutions required for hydroxamate moiety to exhibit enhanced inhibitory activity against HDAC4. The reported compounds demonstrated good binding and thus can be considered as potent therapeutic leads against ataxia. PMID:26510381

  12. Fragment based G-QSAR and molecular dynamics based mechanistic simulations into hydroxamic-based HDAC inhibitors against spinocerebellar ataxia.

    PubMed

    Sinha, Siddharth; Tyagi, Chetna; Goyal, Sukriti; Jamal, Salma; Somvanshi, Pallavi; Grover, Abhinav

    2016-10-01

    Expansion of polyglutamine (CAG) triplets within the coding gene ataxin 2 results in transcriptional repression, forming the molecular basis of the neurodegenerative disorder named spinocerebellar ataxia type-2 (SCA2). HDAC inhibitors (HDACi) have been elements of great interest in polyglutamine disorders such as Huntington's and Ataxia's. In this study, we have selected hydroxamic acid derivatives as HDACi and performed fragment-based G-QSAR, molecular docking studies and molecular dynamics simulations for elucidating the dynamic mode of action of HDACi with His-Asp catalytic dyad of HDAC4. The model was statistically validated to establish its predictive robustness. The model was statistically significant with r(2) value of .6297, cross-validated co-relation coefficient q(2) value of .5905 and pred_r(2) (predicted square co-relation coefficient) value of .85. An F-test value of 56.11 confirms absolute robustness of the model. Two combinatorial libraries comprising of 3180 compounds were created with hydroxamate moiety as the template and their pIC50 activities were predicted based on the G-QSAR model. The combinatorial library created was screened on the basis of predicted activity (pIC50), with two resultant top scoring compounds, HIC and DHC. The interaction of the compounds with His-Asp dyad in terms of H-bond interactions with His802, Asp840, Pro942, and Gly975 residues of HDAC4 was evaluated by docking and 20 ns long molecular dynamics simulations. This study provides valuable leads for structural substitutions required for hydroxamate moiety to exhibit enhanced inhibitory activity against HDAC4. The reported compounds demonstrated good binding and thus can be considered as potent therapeutic leads against ataxia.

  13. A New Graph-Based Molecular Descriptor Using the Canonical Representation of the Molecule

    PubMed Central

    Hentabli, Hamza; Abdo, Ammar; Salim, Naomie

    2014-01-01

    Molecular similarity is a pervasive concept in drug design. The basic idea underlying molecular similarity is the similar property principle, which states that structurally similar molecules will exhibit similar physicochemical and biological properties. In this paper, a new graph-based molecular descriptor (GBMD) is introduced. The GBMD is a new method of obtaining a rough description of 2D molecular structure in textual form based on the canonical representations of the molecule outline shape and it allows rigorous structure specification using small and natural grammars. Simulated virtual screening experiments with the MDDR database show clearly the superiority of the graph-based descriptor compared to many standard descriptors (ALOGP, MACCS, EPFP4, CDKFP, PCFP, and SMILE) using the Tanimoto coefficient (TAN) and the basic local alignment search tool (BLAST) when searches were carried. PMID:25140330

  14. A new graph-based molecular descriptor using the canonical representation of the molecule.

    PubMed

    Hentabli, Hamza; Saeed, Faisal; Abdo, Ammar; Salim, Naomie

    2014-01-01

    Molecular similarity is a pervasive concept in drug design. The basic idea underlying molecular similarity is the similar property principle, which states that structurally similar molecules will exhibit similar physicochemical and biological properties. In this paper, a new graph-based molecular descriptor (GBMD) is introduced. The GBMD is a new method of obtaining a rough description of 2D molecular structure in textual form based on the canonical representations of the molecule outline shape and it allows rigorous structure specification using small and natural grammars. Simulated virtual screening experiments with the MDDR database show clearly the superiority of the graph-based descriptor compared to many standard descriptors (ALOGP, MACCS, EPFP4, CDKFP, PCFP, and SMILE) using the Tanimoto coefficient (TAN) and the basic local alignment search tool (BLAST) when searches were carried. PMID:25140330

  15. Interaction of a Julolidine-Based Neutral Ultrafast Molecular Rotor with Natural DNA: Spectroscopic and Molecular Docking Studies.

    PubMed

    Kalel, Rahul; Mora, Aruna K; Ghosh, Rajib; Dhavale, Dilip D; Palit, Dipak K; Nath, Sukhendu

    2016-09-22

    Ultrafast molecular rotors (UMRs) are reported to be one of the best fluorescent sensors to study different microenvironments, including biomolecules. In the present work, we have explored the possibility of application of a julolidine-based neutral UMR, 9-(2,2-dicyano vinyl) julolidine (DCVJ), as a DNA sensor and studied its mode of binding with DNA in detail using spectroscopic and molecular docking techniques. Our spectroscopic studies indicate that association of DCVJ with DNA leads to a very large enhancement in its emission intensity. Detailed investigation reveals that, despite being a neutral molecule, binding of DCVJ with DNA is largely modulated in the presence of salt. Such an unusual salt effect has been explained by invoking the ion-dipole interaction between DCVJ and the phosphate backbone of DNA. The ion-dipole interaction has also been established by studying the interaction of DCVJ with nucleosides. Detailed time-resolved studies show that the twisting motion around the vinyl bond in DCVJ gets retarded to a great extent because of its association with DNA molecules. Through competitive binding studies, it has also been established that DCVJ also binds to DNA through intercalation. Finally, quantum chemical calculations and molecular docking studies have been performed to confirm the mode of binding of DCVJ with DNA. PMID:27559832

  16. Density functional theory based study of molecular interactions, recognition, engineering, and quantum transport in π molecular systems.

    PubMed

    Cho, Yeonchoo; Cho, Woo Jong; Youn, Il Seung; Lee, Geunsik; Singh, N Jiten; Kim, Kwang S

    2014-11-18

    CONSPECTUS: In chemical and biological systems, various interactions that govern the chemical and physical properties of molecules, assembling phenomena, and electronic transport properties compete and control the microscopic structure of materials. The well-controlled manipulation of each component can allow researchers to design receptors or sensors, new molecular architectures, structures with novel morphology, and functional molecules or devices. In this Account, we describe the structures and electronic and spintronic properties of π-molecular systems that are important for controlling the architecture of a variety of carbon-based systems. Although DFT is an important tool for describing molecular interactions, the inability of DFT to accurately represent dispersion interactions has made it difficult to properly describe π-interactions. However, the recently developed dispersion corrections for DFT have allowed us to include these dispersion interactions cost-effectively. We have investigated noncovalent interactions of various π-systems including aromatic-π, aliphatic-π, and non-π systems based on dispersion-corrected DFT (DFT-D). In addition, we have addressed the validity of DFT-D compared with the complete basis set (CBS) limit values of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)] and Møller-Plesset second order perturbation theory (MP2). The DFT-D methods are still unable to predict the correct ordering in binding energies within the benzene dimer and the cyclohexane dimer. Nevertheless, the overall DFT-D predicted binding energies are in reasonable agreement with the CCSD(T) results. In most cases, results using the B97-D3 method closely reproduce the CCSD(T) results with the optimized energy-fitting parameters. On the other hand, vdW-DF2 and PBE0-TS methods estimate the dispersion energies from the calculated electron density. In these approximations, the interaction energies around the equilibrium

  17. Polyphosphazene Based Star-Branched and Dendritic Molecular Brushes.

    PubMed

    Henke, Helena; Posch, Sandra; Brüggemann, Oliver; Teasdale, Ian

    2016-05-01

    A new synthetic procedure is described for the preparation of poly(organo)phosphazenes with star-branched and star dendritic molecular brush type structures, thus describing the first time it has been possible to prepare controlled, highly branched architectures for this type of polymer. Furthermore, as a result of the extremely high-arm density generated by the phosphazene repeat unit, the second-generation structures represent quite unique architectures for any type of polymer. Using two relativity straight forward iterative syntheses it is possible to prepare globular highly branched polymers with up to 30 000 functional end groups, while keeping relatively narrow polydispersities (1.2-1.6). Phosphine mediated polymerization of chlorophosphoranimine is first used to prepare three-arm star polymers. Subsequent substitution with diphenylphosphine moieties gives poly(organo)phosphazenes to function as multifunctional macroinitiators for the growth of a second generation of polyphosphazene arms. Macrosubstitution with Jeffamine oligomers gives a series of large, water soluble branched macromolecules with high-arm density and hydrodynamic diameters between 10 and 70 nm. PMID:27027404

  18. Polyphosphazene Based Star-Branched and Dendritic Molecular Brushes.

    PubMed

    Henke, Helena; Posch, Sandra; Brüggemann, Oliver; Teasdale, Ian

    2016-05-01

    A new synthetic procedure is described for the preparation of poly(organo)phosphazenes with star-branched and star dendritic molecular brush type structures, thus describing the first time it has been possible to prepare controlled, highly branched architectures for this type of polymer. Furthermore, as a result of the extremely high-arm density generated by the phosphazene repeat unit, the second-generation structures represent quite unique architectures for any type of polymer. Using two relativity straight forward iterative syntheses it is possible to prepare globular highly branched polymers with up to 30 000 functional end groups, while keeping relatively narrow polydispersities (1.2-1.6). Phosphine mediated polymerization of chlorophosphoranimine is first used to prepare three-arm star polymers. Subsequent substitution with diphenylphosphine moieties gives poly(organo)phosphazenes to function as multifunctional macroinitiators for the growth of a second generation of polyphosphazene arms. Macrosubstitution with Jeffamine oligomers gives a series of large, water soluble branched macromolecules with high-arm density and hydrodynamic diameters between 10 and 70 nm.

  19. Phthalocyanine-Based Molecularly Imprinted Polymers as Nucleoside Receptors

    PubMed Central

    Longo, Luigia; Vasapollo, Giuseppe

    2008-01-01

    A molecularly imprinted polymer (MIP) for tri-O-acetyladenosine (TOAA), PPM(TOAA), was prepared by the combined use of methacrylic acid (MAA) and Zn(II)tetra(4′-methacryloxyphenoxy) phthalocyanine as functional monomers. This MIP exhibited a higher binding ability for TOAA compared to the MIP prepared using only MAA, PM(TOAA), in batch rebinding tests. Scatchard analysis gave a higher association constant of PPM(TOAA) for TOAA (2.96×104 M−1) than that of PM(TOAA) (1.48×104 M−1). The MIP prepared using only the zinc-phthalocyanine, PP(TOAA), did not show any binding capacity for TOAA. This means that the phthalocyanine in the MIP contributes to higher affinities, although it barely interacts with TOAA. Since selectivity for this kind of MIPs is more important than binding affinity, the binding of TOAA and a structurally related compound, tri-O-acetyluridine (TOAU), on the polymers was investigated. Both PPM(TOAA) and PM(TOAA) exhibited binding affinities for TOAA while they did not show any binding capacity for TOAU. PMID:18288245

  20. Polyphosphazene Based Star-Branched and Dendritic Molecular Brushes

    PubMed Central

    Henke, Helena; Posch, Sandra; Brüggemann, Oliver; Teasdale, Ian

    2016-01-01

    A new synthetic procedure is described for the preparation of poly(organo)phosphazenes with star-branched and star dendritic molecular brush type structures, thus describing the first time it has been possible to prepare controlled, highly branched architectures for this type of polymer. Furthermore, as a result of the extremely high-arm density generated by the phosphazene repeat unit, the second-generation structures represent quite unique architectures for any type of polymer. Using two relativity straight forward iterative syntheses it is possible to prepare globular highly branched polymers with up to 30 000 functional end groups, while keeping relatively narrow polydispersities (1.2–1.6). Phosphine mediated polymerization of chlorophosphoranimine is first used to prepare three-arm star polymers. Subsequent substitution with diphenylphosphine moieties gives poly(organo)phosphazenes to function as multifunctional macroinitiators for the growth of a second generation of polyphosphazene arms. Macrosubstitution with Jeffamine oligomers gives a series of large, water soluble branched macromolecules with high-arm density and hydrodynamic diameters between 10 and 70 nm. PMID:27027404

  1. Molecular and biomolecular-based nanomaterials: Tubulin and taxol as molecular constituents

    NASA Astrophysics Data System (ADS)

    Castro Carmona, Javier Servando

    The new field of protein-based nano-technology takes advantage of the complex interactions between proteins to form unique structures with properties that cannot be achieved with traditional components. Microtubules (MTs), self assembled proteinaceous hollow filaments, offer promise in the development of MT-based nano-systems. The compelling need for the controlled assembly of 3D MT arrays is the fundamental motivation for the first part of this research. We report on the morphology of MTs grown in a crowded environment in the form of high viscosity fluids containing agarose and a novel process that enables the assembly of MTs supported by gel-based 3D scaffolds. Our research on MTs and their interaction with other molecules lead us to discover extraordinary spherulitic structures that changed the course of the project. The novel subject situate us into a complicated dilemma that question the nature of MT asters reported in experiments carried out in cells. The second part of this research is focused in the crystallization of Taxol, a MT stabilizing molecule used as anti-cancer drug. It was confirmed via fluorescent and differential interference contrast microscopy that Taxol crystals can be decorated with fluorescent proteins and fluorochromes without perturbing their morphology. We used theoretical calculations to further investigate Taxol-fluorescent agent interactions. Furthermore, the crystallization of Taxol was studied in pure water, aqueous solutions containing tubulin proteins and tubulin-containing agarose gels. We demonstrated that tubulin is able to heterogeneously nucleate Taxol spherulites. To explain the formation of tubulin-Taxol nuclei a new, secondary Taxol-binding site within the tubulin heterodimer is suggested. Results presented in this work are important for in vivo and in vitro microtubule studies due to the possibility of mistaking these Taxol spherulites for microtubule asters. Thus, we are confirming the need for careful interpretation of

  2. A communication theoretical analysis of FRET-based mobile ad hoc molecular nanonetworks.

    PubMed

    Kuscu, Murat; Akan, Ozgur B

    2014-09-01

    Nanonetworks refer to a group of nanosized machines with very basic operational capabilities communicating to each other in order to accomplish more complex tasks such as in-body drug delivery, or chemical defense. Realizing reliable and high-rate communication between these nanomachines is a fundamental problem for the practicality of these nanonetworks. Recently, we have proposed a molecular communication method based on Förster Resonance Energy Transfer (FRET) which is a nonradiative excited state energy transfer phenomenon observed among fluorescent molecules, i.e., fluorophores. We have modeled the FRET-based communication channel considering the fluorophores as single-molecular immobile nanomachines, and shown its reliability at high rates, and practicality at the current stage of nanotechnology. In this study, for the first time in the literature, we investigate the network of mobile nanomachines communicating through FRET. We introduce two novel mobile molecular nanonetworks: FRET-based mobile molecular sensor/actor nanonetwork (FRET-MSAN) which is a distributed system of mobile fluorophores acting as sensor or actor node; and FRET-based mobile ad hoc molecular nanonetwork (FRET-MAMNET) which consists of fluorophore-based nanotransmitter, nanoreceivers and nanorelays. We model the single message propagation based on birth-death processes with continuous time Markov chains. We evaluate the performance of FRET-MSAN and FRET-MAMNET in terms of successful transmission probability and mean extinction time of the messages, system throughput, channel capacity and achievable communication rates.

  3. [Molecular engineering of cellulase catalytic domain based on glycoside hydrolase family].

    PubMed

    Zhang, Xiaomei; Li, Dandan; Wang, Lushan; Zhao, Yue; Chen, Guanjun

    2013-04-01

    Molecular engineering of cellulases can improve enzymatic activity and efficiency. Recently, the Carbohydrate-Active enZYmes Database (CAZy), including glycoside hydrolase (GH) families, has been established with the development of Omics and structural measurement technologies. Molecular engineering based on GH families can obviously decrease the probing space of target sequences and structures, and increase the odds of experimental success. Besides, the study of cellulase active-site architecture paves the way toward the explanation of catalytic mechanism. This review focuses on the main GH families and the latest progresses in molecular engineering of catalytic domain. Based on the combination of analysis of a large amount of data in the same GH family and their conservative active-site architecture information, rational design will be an important direction for molecular engineering and promote the rapid development of the conversion of biomass. PMID:23894816

  4. Simple nanoparticle-based luminometric method for molecular weight determination of polymeric compounds.

    PubMed

    Pihlasalo, Sari; Virtamo, Maria; Legrand, Nicolas; Hänninen, Pekka; Härmä, Harri

    2014-01-21

    A nanoparticle-based method utilizing time-resolved luminescence resonance energy transfer (TR-LRET) was developed for molecular weight determination. This mix-and-measure nanoparticle method is based on the competitive adsorption between the analyte and the acceptor-labeled protein to donor Eu(III) nanoparticles. The size-dependent adsorption of molecules enables the molecular weight determination of differently sized polymeric compounds down to a concentration level of micrograms per liter. The molecular weight determination from 1 to 10 kDa for polyamino acids and from 0.3 to 70 kDa for polyethylene imines is demonstrated. The simple and cost-effective nanoparticle method as microtiter plate assay format shows great potential for the detection of the changes in molecular weight or for quantification of differently sized molecules in biochemical laboratories and in industrial polymeric processes.

  5. Molecular spies for bioimaging--fluorescent protein-based probes.

    PubMed

    Miyawaki, Atsushi; Niino, Yusuke

    2015-05-21

    Convergent advances in optical imaging and genetic engineering have fueled the development of new technologies for biological visualization. Those technologies include genetically encoded indicators based on fluorescent proteins (FPs) for imaging ions, molecules, and enzymatic activities "to spy on cells," as phrased by Roger Tsien, by sneaking into specific tissues, cell types, or subcellular compartments, and reporting on specific intracellular activities. Here we review the current range of unimolecular indicators whose working principle is the conversion of a protein conformational change into a fluorescence signal. Many of the indicators have been developed from fluorescence resonance energy transfer- and single-FP-based approaches. PMID:26000848

  6. Large magnetoresistance of paracyclophane-based molecular tunnel junctions: A first-principles study

    SciTech Connect

    Tao, L. L.; Liang, S. H.; Liu, D. P.; Han, X. F.

    2013-12-07

    We report a theoretical study of magnetoresistance and spin-polarized transport of a series of paracyclophane-based molecular tunnel junctions. We predict that the molecular tunnel junction using [2.2]-paracyclophane barrier has the desired low resistance area product in combination with high magnetoresistance ratio. In addition, we find the spin-polarized conductance decreases exponentially with increasing the molecular length, indicating a nonresonant tunneling mechanism. In particular, the characteristic decay constant can be theoretically evaluated from the complex band structure of periodic paracyclophane molecule. The spin-polarized transport mechanism is systematically analyzed.

  7. Influence of carbon curvature on molecular adsorptions in carbon-based materials: a force field approach.

    PubMed

    Kostov, M K; Cheng, H; Cooper, A C; Pez, G P

    2002-09-30

    A general force field methodology is developed for description of molecular interactions in carbon-based materials. The method makes use of existing parameters of potential functions developed for sp(2) and sp(3) carbons and allows accurate representation of molecular forces in curved carbon environment. The potential parameters are explicitly curvature and site dependent. The proposed force field approach was used in molecular dynamics (MD) simulations for hydrogen adsorption in single-walled carbon nanotubes (SWNTs). The results reveal significant nanotube deformations and the calculated energies of adsorption are comparable to the reported experimental heat of adsorption for H2 in SWNTs. PMID:12366059

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

    PubMed

    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. PMID:27251307

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

    PubMed

    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.

  10. Foraging on the potential energy surface: a swarm intelligence-based optimizer for molecular geometry.

    PubMed

    Wehmeyer, Christoph; Falk von Rudorff, Guido; Wolf, Sebastian; Kabbe, Gabriel; Schärf, Daniel; Kühne, Thomas D; Sebastiani, Daniel

    2012-11-21

    We present a stochastic, swarm intelligence-based optimization algorithm for the prediction of global minima on potential energy surfaces of molecular cluster structures. Our optimization approach is a modification of the artificial bee colony (ABC) algorithm which is inspired by the foraging behavior of honey bees. We apply our modified ABC algorithm to the problem of global geometry optimization of molecular cluster structures and show its performance for clusters with 2-57 particles and different interatomic interaction potentials. PMID:23181297

  11. NLP-based information extraction for managing the molecular biology literature.

    PubMed

    Libbus, Bisharah; Rindflesch, Thomas C

    2002-01-01

    We present research aimed at devising a tool for using natural language processing to identify and extract biomedical information from text for the purpose of assisting researchers in molecular biology manage large amounts of information. A pilot project based on the molecular genetics of diabetes demonstrates our ability to explore the interaction of genomic phenomena and clinical findings. We suggest the cooperation of this extracted information with systems for clustering text and constructing labeled networks of data. PMID:12463863

  12. Foraging on the potential energy surface: A swarm intelligence-based optimizer for molecular geometry

    NASA Astrophysics Data System (ADS)

    Wehmeyer, Christoph; Falk von Rudorff, Guido; Wolf, Sebastian; Kabbe, Gabriel; Schärf, Daniel; Kühne, Thomas D.; Sebastiani, Daniel

    2012-11-01

    We present a stochastic, swarm intelligence-based optimization algorithm for the prediction of global minima on potential energy surfaces of molecular cluster structures. Our optimization approach is a modification of the artificial bee colony (ABC) algorithm which is inspired by the foraging behavior of honey bees. We apply our modified ABC algorithm to the problem of global geometry optimization of molecular cluster structures and show its performance for clusters with 2-57 particles and different interatomic interaction potentials.

  13. New molecular descriptors based on local properties at the molecular surface and a boiling-point model derived from them.

    PubMed

    Ehresmann, Bernd; de Groot, Marcel J; Alex, Alexander; Clark, Timothy

    2004-01-01

    New molecular descriptors based on statistical descriptions of the local ionization potential, local electron affinity, and the local polarizability at the surface of the molecule are proposed. The significance of these descriptors has been tested by calculating them for the Maybridge database in addition to our set of 26 descriptors reported previously. The new descriptors show little correlation with those already in use. Furthermore, the principal components of the extended set of descriptors for the Maybridge data show that especially the descriptors based on the local electron affinity extend the variance in our set of descriptors, which we have previously shown to be relevant to physical properties. The first nine principal components are shown to be most significant. As an example of the usefulness of the new descriptors, we have set up a QSPR model for boiling points using both the old and new descriptors.

  14. GIS based Relative Tsunami Hazard Maps for Northern California, Humboldt and Del Norte Counties

    NASA Astrophysics Data System (ADS)

    Patton, J. R.; Dengler, L. A.

    2004-12-01

    Tsunami hazard maps are generated using a geographical information systems (GIS) approach to depict the relative tsunami hazard of coastal Humboldt and Del Norte Counties in northern California. Maps are composed for the Humboldt Bay, Eel River, and Crescent City regions and available online at http://www.humboldt.edu/~geodept/earthquakes/rctwg/toc.html . In contrast to previous mapping efforts that utilize a single line to represent inundation, hazard is displayed gradationally. A 2.5D surface is constructed to represent this hazard. Elevation, normally used for 2.5D surfaces, is substituted with hazard units. Criteria boundaries are used to separate regions of increasing hazard. Criteria boundaries are defined based on numerical modeling, paleoseismic studies, historical flooding, FEMA Q3 flood maps, and impacts of recent tsunamis elsewhere. Zones are constructed to further adjust the criteria with respect to a physically determined variable hazard (e.g. proximity to open ocean). A triangular irregular network (TIN) is constructed using hazard criteria boundaries as breaklines. Fabricated points are necessary to construct a hazard surface and are placed where criteria boundaries diverge or where hazard is nonlinear between criteria boundaries. Hazard is displayed as a continuous gradational color scale ranging from red (high hazard) through orange (medium), yellow (low) to gray (no hazard). The maps are GIS based to facilitate ready adaptation by planners and emergency managers. The maps are intended for educational purposes, to improve awareness of tsunami hazards and to encourage emergency planning efforts of local and regional organizations by illustrating the range of possible tsunami events.

  15. Microbial detection method based on sensing molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Wilkins, J. R.; Stoner, G. E.; Boykin, E. H.

    1974-01-01

    A simple method for detecting bacteria, based on the time of hydrogen evolution, was developed and tested against various members of the Enterobacteriaceae group. The test system consisted of (1) two electrodes, platinum and a reference electrode, (2) a buffer amplifier, and (3) a strip-chart recorder. Hydrogen evolution was measured by an increase in voltage in the negative (cathodic) direction. A linear relationship was established between inoculum size and the time hydrogen was detected (lag period). Lag times ranged from 1 h for 1 million cells/ml to 7 h for 1 cell/ml. For each 10-fold decrease in inoculum, length of the lag period increased 60 to 70 min. Based on the linear relationship between inoculum and lag period, these results indicate the potential application of the hydrogen-sensing method for rapidly detecting coliforms and other gas-producing microorganisms in a variety of clinical, food, and other samples.

  16. Lewis Acid-Base, Molecular Modeling, and Isotopic Labeling in a Sophomore Inorganic Chemistry Laboratory

    ERIC Educational Resources Information Center

    Nataro, Chip; Ferguson, Michelle A.; Bocage, Katherine M.; Hess, Brian J.; Ross, Vincent J.; Swarr, Daniel T.

    2004-01-01

    An experiment to prepare a deuterium labeled adduct of a Lewis acid and Lewis base, to use computational methods allowing students to visualize the LUMO of Lewis acids, the HOMO of Lewis bases and the molecular orbitals of the adduct that is formed is developed. This allows students to see the interplay between calculated and experimental results.

  17. The formation of ZnO-based coatings from solutions containing high-molecular polyvinylpyrrolidone

    NASA Astrophysics Data System (ADS)

    Evstrop'ev, S. K.; Soshnikov, I. P.; Khrebtov, A. I.

    2016-05-01

    A method for deposition of transparent nanosize ZnO-based coatings on the glass surface from solutions containing high-molecular polyvinylpyrrolidone is described. The method can be used to form transparent homogeneous coatings based on ZnO with an increased energy gap width. It does not require any intricate technological equipment.

  18. Polarization conversion-based molecular sensing using anisotropic plasmonic metasurfaces

    NASA Astrophysics Data System (ADS)

    Verre, R.; Maccaferri, N.; Fleischer, K.; Svedendahl, M.; Odebo Länk, N.; Dmitriev, A.; Vavassori, P.; Shvets, I. V.; Käll, M.

    2016-05-01

    Anisotropic media induce changes in the polarization state of transmitted and reflected light. Here we combine this effect with the refractive index sensitivity typical of plasmonic nanoparticles to experimentally demonstrate self-referenced single wavelength refractometric sensing based on polarization conversion. We fabricated anisotropic plasmonic metasurfaces composed of gold dimers and, as a proof of principle, measured the changes in the rotation of light polarization induced by biomolecular adsorption with a surface sensitivity of 0.2 ng cm-2. We demonstrate the possibility of miniaturized sensing and we show that experimental results can be reproduced by analytical theory. Various ways to increase the sensitivity and applicability of the sensing scheme are discussed.Anisotropic media induce changes in the polarization state of transmitted and reflected light. Here we combine this effect with the refractive index sensitivity typical of plasmonic nanoparticles to experimentally demonstrate self-referenced single wavelength refractometric sensing based on polarization conversion. We fabricated anisotropic plasmonic metasurfaces composed of gold dimers and, as a proof of principle, measured the changes in the rotation of light polarization induced by biomolecular adsorption with a surface sensitivity of 0.2 ng cm-2. We demonstrate the possibility of miniaturized sensing and we show that experimental results can be reproduced by analytical theory. Various ways to increase the sensitivity and applicability of the sensing scheme are discussed. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01336h

  19. Bio-molecular sensors based on guided mode resonance filters

    NASA Astrophysics Data System (ADS)

    Saleem, M. R.; Ali, R.; Honkanen, S.; Turunen, J.

    2016-08-01

    In this work a low surface roughness and homogenous, high refractive index, and amorphous TiO2 layer on corrugated structures of diffractive optical element is coated by Atomic Layer Deposition (ALD) for biosensors. The design of Guided Mode Resonance Filters (GMRFs) is based on refractive indices and thicknesses of the waveguide biomolecular layers. The designed spectral shifts are calculated by Fourier Modal Method (FMM) and depend on the magnitude of the variations in refractive index of the biomolecular layer on waveguide structures. Furthermore, the sensitivity of the biomolecular sensors depends on the thickness of biomolecular layer and periodicity of the structures. The waveguide structures designed for larger periods show an enhancement in the sensitivity (nm/RIU) of the biomolecular sensor at longer wavelengths. The periodicities of nanophotonic structures are varied from 300 to 500 nm in design calculations with predominance of increase in effective index of the structure to support leaky waveguide modes.

  20. Pulsed diode laser-based monitor for singlet molecular oxygen

    PubMed Central

    Lee, Seonkyung; Zhu, Leyun; Minhaj, Ahmed M.; Hinds, Michael F.; Vu, Danthu H.; Rosen, David I.; Davis, Steven J.; Hasan, Tayyaba

    2010-01-01

    Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1Δ) are believed to be the species that destroys cancerous cells during PDT. Monitoring singlet oxygen produced by PDT may lead to more precise and effective PDT treatments. Our approach uses a pulsed diode laser-based monitor with optical fibers and a fast data acquisition system to monitor singlet oxygen during PDT. We present results of in vitro singlet oxygen detection in solutions and in a rat prostate cancer cell line as well as PDT mechanism modeling. PMID:18601555

  1. Pulsed diode laser-based monitor for singlet molecular oxygen.

    PubMed

    Lee, Seonkyung; Zhu, Leyun; Minhaj, Ahmed M; Hinds, Michael F; Vu, Danthu H; Rosen, David I; Davis, Steven J; Hasan, Tayyaba

    2008-01-01

    Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1Delta) are believed to be the species that destroys cancerous cells during PDT. Monitoring singlet oxygen produced by PDT may lead to more precise and effective PDT treatments. Our approach uses a pulsed diode laser-based monitor with optical fibers and a fast data acquisition system to monitor singlet oxygen during PDT. We present results of in vitro singlet oxygen detection in solutions and in a rat prostate cancer cell line as well as PDT mechanism modeling.

  2. Molecular Systematics of Polygonum minus Huds. Based on ITS Sequences

    PubMed Central

    Bunawan, Hamidun; Choong, Chee Yen; Md-Zain, Badrul Munir; Baharum, Syarul Nataqain; Noor, Normah Mohd

    2011-01-01

    Plastid trnL-trnF and nuclear ribosomal ITS sequences were obtained from selected wild-type individuals of Polygonum minus Huds. in Peninsular Malaysia. The 380 bp trnL-trnF sequences of the Polygonum minus accessions were identical. Therefore, the trnL-trnF failed to distinguish between the Polygonum minus accessions. However, the divergence of ITS sequences (650 bp) among the Polygonum minus accessions was 1%, indicating that these accessions could be distinguished by the ITS sequences. A phylogenetic relationship based on the ITS sequences was inferred using neighbor-joining, maximum parsimony and Bayesian inference. All of the tree topologies indicated that Polygonum minus from Peninsular Malaysia is unique and different from the synonymous Persicaria minor (Huds.) Opiz and Polygonum kawagoeanum Makino. PMID:22174621

  3. High Speed Data Processing for Imaging MS-Based Molecular Histology Using Graphical Processing Units

    NASA Astrophysics Data System (ADS)

    Jones, Emrys A.; van Zeijl, René J. M.; Andrén, Per E.; Deelder, André M.; Wolters, Lex; McDonnell, Liam A.

    2012-04-01

    Imaging MS enables the distributions of hundreds of biomolecular ions to be determined directly from tissue samples. The application of multivariate methods, to identify pixels possessing correlated MS profiles, is referred to as molecular histology as tissues can be annotated on the basis of the MS profiles. The application of imaging MS-based molecular histology to larger tissue series, for clinical applications, requires significantly increased computational capacity in order to efficiently analyze the very large, highly dimensional datasets. Such datasets are highly suited to processing using graphical processor units, a very cost-effective solution for high speed processing. Here we demonstrate up to 13× speed improvements for imaging MS-based molecular histology using off-the-shelf components, and demonstrate equivalence with CPU based calculations. It is then discussed how imaging MS investigations may be designed to fully exploit the high speed of graphical processor units.

  4. Manganese-Based Molecular Electrocatalysts for Oxidation of Hydrogen

    SciTech Connect

    Hulley, Elliott; Kumar, Neeraj; Raugei, Simone; Bullock, R. Morris

    2015-10-05

    Oxidation of H2 (1 atm) is catalyzed by the manganese electrocatalysts [(P2N2)MnI(CO)(bppm)]+ and [(PNP)MnI(CO)(bppm)]+ (P2N2= 1,5-dibenzyl-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane; PNP = (Ph2PCH2)2NMe); bppm = (PArF2)2CH2, and ArF = 3,5-(CF3)2C6H3). In fluorobenzene solvent using 2,6-lutidine as the exogeneous base, the turnover frequency for [(P2N2)MnI(CO)(bppm)]+ is 3.5 s-1 with an estimated overpotential of 590 mV. For [(PNP)MnI(CO)(bppm)], in fluorobenzene solvent using N-methylpyrrolidine as the exogeneous base, the turnover frequency is 1.4 s-1 with an estimated overpotential of 700 mV. Density functional theory calculations suggest that the slow step in the catalytic cycle is proton transfer from the oxidized 17-electron manganese hydride, e.g., [(P2N2)MnIIH(CO)(bppm)]+ to the pendant amine. The computed activation barrier for intramolecular proton transfer from the metal to the pendant amine is 20.4 kcal/mol in [(P2N2)MnIIH(CO)(bppm)]+ and 21.3 kcal/mol in [(PNP)MnI(CO)(bppm)]. The high barrier appears to result from both the unfavorability of metal-to-nitrogen proton transfer (thermodynamically uphill by 6.6 pKa units, 9 kcal/mol), as well as the relatively long manganese-nitrogen separation in the MnIIH complexes.

  5. Gd-based macromolecules and nanoparticles as magnetic resonance contrast agents for molecular imaging

    PubMed Central

    Huang, Ching-Hui; Tsourkas, Andrew

    2013-01-01

    As we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice. Magnetic resonance (MR) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes. One promising new direction in the development of MR contrast agents involves the labeling and/or loading of nanoparticles with gadolinium (Gd). These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies. In this review, we discuss some of the progress that has recently been made in the development of Gd-based macromolecules and nanoparticles and outline some of the physical and chemical properties that will be important to incorporate into the next generation of contrast agents, including high Gd chelate stability, high “relaxivity per particle” and “relaxivity density”, and biodegradability. PMID:23432004

  6. Molecular-based identification of yeasts isolated from bovine clinical mastitis in Japan.

    PubMed

    Hayashi, Tomohito; Sugita, Takashi; Hata, Eiji; Katsuda, Ken; Zhang, Enshi; Kiku, Yoshio; Sugawara, Kazue; Ozawa, Tomomi; Matsubara, Tomoko; Ando, Takaaki; Obayashi, Tetsu; Ito, Takaaki; Yabusaki, Takahiro; Kudo, Katsunori; Yamamoto, Hiroshi; Koiwa, Masateru; Oshida, Toshio; Tagawa, Yuichi; Kawai, Kazuhiro

    2013-01-01

    This study analyzed molecular-based identification of yeasts that associated with bovine clinical mastitis in Japan. Over 3,200 quarter milk samples from Holstein dairy cows collected in 2011 on Hokkaido and Honshu islands were examined. Yeast isolates were characterized by polymerase chain reaction amplification and sequencing of the D1/D2 region of the 26S rDNA. Molecular characterization confirmed that Candida spp. and Pichia spp. were most frequently isolated species. Our molecular analysis of mastitic milk samples demonstrated the prevalence of Pichia kudriavzevii(22/58) and Candida tropicalis(14/58). In addition, we demonstrated that molecular analysis of the D1/D2 region of the 26S rDNA is a rapid and reliable method for identifying clinically significant yeasts in dairy hygiene, including potentially new or emerging pathogenic species. PMID:23100116

  7. Electronic shift register memory based on molecular electron-transfer reactions

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

    The design of a shift register memory at the molecular level is described in detail. The memory elements are based on a chain of electron-transfer molecules incorporated on a very large scale integrated (VLSI) substrate, and the information is shifted by photoinduced electron-transfer reactions. The design requirements for such a system are discussed, and several realistic strategies for synthesizing these systems are presented. The immediate advantage of such a hybrid molecular/VLSI device would arise from the possible information storage density. The prospect of considerable savings of energy per bit processed also exists. This molecular shift register memory element design solves the conceptual problems associated with integrating molecular size components with larger (micron) size features on a chip.

  8. Computational design of intrinsic molecular rectifiers based on asymmetric functionalization of N-phenylbenzamide

    SciTech Connect

    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.

    2015-12-08

    Here, 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.

  9. Computational design of intrinsic molecular rectifiers based on asymmetric functionalization of N-phenylbenzamide

    DOE PAGESBeta

    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.

    2015-11-03

    Here, 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 findingsmore » 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.« less

  10. Computational design of intrinsic molecular rectifiers based on asymmetric functionalization of N-phenylbenzamide

    SciTech Connect

    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.

    2015-11-03

    Here, 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.

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

    PubMed

    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.

  12. Molecular evidence of Burkholderia pseudomallei genotypes based on geographical distribution

    PubMed Central

    Zulkefli, Noorfatin Jihan; Mariappan, Vanitha; Vellasamy, Kumutha Malar; Chong, Chun Wie; Thong, Kwai Lin; Ponnampalavanar, Sasheela; Vadivelu, Jamuna

    2016-01-01

    Background. Central intermediary metabolism (CIM) in bacteria is defined as a set of metabolic biochemical reactions within a cell, which is essential for the cell to survive in response to environmental perturbations. The genes associated with CIM are commonly found in both pathogenic and non-pathogenic strains. As these genes are involved in vital metabolic processes of bacteria, we explored the efficiency of the genes in genotypic characterization of Burkholderia pseudomallei isolates, compared with the established pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) schemes. Methods. Nine previously sequenced B. pseudomallei isolates from Malaysia were characterized by PFGE, MLST and CIM genes. The isolates were later compared to the other 39 B. pseudomallei strains, retrieved from GenBank using both MLST and sequence analysis of CIM genes. UniFrac and hierachical clustering analyses were performed using the results generated by both MLST and sequence analysis of CIM genes. Results. Genetic relatedness of nine Malaysian B. pseudomallei isolates and the other 39 strains was investigated. The nine Malaysian isolates were subtyped into six PFGE profiles, four MLST profiles and five sequence types based on CIM genes alignment. All methods demonstrated the clonality of OB and CB as well as CMS and THE. However, PFGE showed less than 70% similarity between a pair of morphology variants, OS and OB. In contrast, OS was identical to the soil isolate, MARAN. To have a better understanding of the genetic diversity of B. pseudomallei worldwide, we further aligned the sequences of genes used in MLST and genes associated with CIM for the nine Malaysian isolates and 39 B. pseudomallei strains from NCBI database. Overall, based on the CIM genes, the strains were subtyped into 33 profiles where majority of the strains from Asian countries were clustered together. On the other hand, MLST resolved the isolates into 31 profiles which formed three clusters

  13. SWIFT MODELLER: a Java based GUI for molecular modeling.

    PubMed

    Mathur, Abhinav; Shankaracharya; Vidyarthi, Ambarish S

    2011-10-01

    MODELLER is command line argument based software which requires tedious formatting of inputs and writing of Python scripts which most people are not comfortable with. Also the visualization of output becomes cumbersome due to verbose files. This makes the whole software protocol very complex and requires extensive study of MODELLER manuals and tutorials. Here we describe SWIFT MODELLER, a GUI that automates formatting, scripting and data extraction processes and present it in an interactive way making MODELLER much easier to use than before. The screens in SWIFT MODELLER are designed keeping homology modeling in mind and their flow is a depiction of its steps. It eliminates the formatting of inputs, scripting processes and analysis of verbose output files through automation and makes pasting of the target sequence as the only prerequisite. Jmol (3D structure visualization tool) has been integrated into the GUI which opens and demonstrates the protein data bank files created by the MODELLER software. All files required and created by the software are saved in a folder named after the work instance's date and time of execution. SWIFT MODELLER lowers the skill level required for the software through automation of many of the steps in the original software protocol, thus saving an enormous amount of time per instance and making MODELLER very easy to work with.

  14. Detecting Molecular Properties by Various Laser-Based Techniques

    SciTech Connect

    Hsin, Tse-Ming

    2007-01-01

    Four different laser-based techniques were applied to study physical and chemical characteristics of biomolecules and dye molecules. These techniques are liole burning spectroscopy, single molecule spectroscopy, time-resolved coherent anti-Stokes Raman spectroscopy and laser-induced fluorescence microscopy. Results from hole burning and single molecule spectroscopy suggested that two antenna states (C708 & C714) of photosystem I from cyanobacterium Synechocystis PCC 6803 are connected by effective energy transfer and the corresponding energy transfer time is ~6 ps. In addition, results from hole burning spectroscopy indicated that the chlorophyll dimer of the C714 state has a large distribution of the dimer geometry. Direct observation of vibrational peaks and evolution of coumarin 153 in the electronic excited state was demonstrated by using the fs/ps CARS, a variation of time-resolved coherent anti-Stokes Raman spectroscopy. In three different solvents, methanol, acetonitrile, and butanol, a vibration peak related to the stretch of the carbonyl group exhibits different relaxation dynamics. Laser-induced fluorescence microscopy, along with the biomimetic containers-liposomes, allows the measurement of the enzymatic activity of individual alkaline phosphatase from bovine intestinal mucosa without potential interferences from glass surfaces. The result showed a wide distribution of the enzyme reactivity. Protein structural variation is one of the major reasons that are responsible for this highly heterogeneous behavior.

  15. Recent advances in molecular electronics based on carbon nanotubes.

    PubMed

    Bourgoin, Jean-Philippe; Campidelli, Stéphane; Chenevier, Pascale; Derycke, Vincent; Filoramo, Arianna; Goffman, Marcelo F

    2010-01-01

    Carbon nanotubes (CNTs) have exceptional physical properties that make them one of the most promising building blocks for future nanotechnologies. They may in particular play an important role in the development of innovative electronic devices in the fields of flexible electronics, ultra-high sensitivity sensors, high frequency electronics, opto-electronics, energy sources and nano-electromechanical systems (NEMS). Proofs of concept of several high performance devices already exist, usually at the single device level, but there remain many serious scientific issues to be solved before the viability of such routes can be evaluated. In particular, the main concern regards the controlled synthesis and positioning of nanotubes. In our opinion, truly innovative use of these nano-objects will come from: (i) the combination of some of their complementary physical properties, such as combining their electrical and mechanical properties, (ii) the combination of their properties with additional benefits coming from other molecules grafted on the nanotubes, and (iii) the use of chemically- or bio-directed self-assembly processes to allow the efficient combination of several devices into functional arrays or circuits. In this article, we outline the main issues concerning the development of carbon nanotubes based electronics applications and review our recent results in the field.

  16. Bioinformatics-Based Molecular Classification of Arthrobacter Plasmids.

    PubMed

    Mihăşan, Marius

    2015-12-01

    The omnipresence of Arthrobacter species in polluted and toxic soils indicates their great potential in environmental biotechnologies, but practical applications of these bacteria are scarce mainly due to the availability of useful genetic engineering tools. Although many fully sequenced Arthrobacter genomes have been deposited in GenBank, little is known about the biology of their plasmids, especially the core functions: replication and partition. In this study the available Arthrobacter plasmid sequences were analyzed in order to identify their putative replication origin. At least the oris from the cryptic plasmids pXZ10142, pCG1, and pBL1 appear to work in this genus. Based on ParA homolog sequences, the Arthrobacter specific plasmids were classified into 4 clades. Iteron-like sequences were identified on most of the plasmids, indicating the position of the putative Arthrobacter specific oris. Although attempts were made to identify the core gene set required for plasmid replication in this genus, it was not possible. The plasmid proteomes showed a rather low similarity.

  17. Biomedical wellness monitoring system based upon molecular markers

    NASA Astrophysics Data System (ADS)

    Ingram, Whitney

    2012-06-01

    We wish to assist caretakers with a sensor monitoring systems for tracking the physiological changes of homealone patients. One goal is seeking biomarkers and modern imaging sensors like stochastic optical reconstruction microscopy (STORM), which has achieved visible imaging at the nano-scale range. Imaging techniques like STORM can be combined with a fluorescent functional marker in a system to capture the early transformation signs from wellness to illness. By exploiting both microscopic knowledge of genetic pre-disposition and the macroscopic influence of epigenetic factors we hope to target these changes remotely. We adopt dual spectral infrared imaging for blind source separation (BSS) to detect angiogenesis changes and use laser speckle imaging for hypertension blood flow monitoring. Our design hypothesis for the monitoring system is guided by the user-friendly, veteran-preferred "4-Non" principles (noninvasive, non-contact, non-tethered, non-stop-to-measure) and by the NIH's "4Ps" initiatives (predictive, personalized, preemptive, and participatory). We augment the potential storage system with the recent know-how of video Compressive Sampling (CSp) from surveillance cameras. In CSp only major changes are saved, which reduces the manpower cost of caretakers and medical analysts. This CSp algorithm is based on smart associative memory (AM) matrix storage: change features and detailed scenes are written by the outer-product and read by the inner product without the usual Harsh index for image searching. From this approach, we attempt to design an effective household monitoring approach to save healthcare costs and maintain the quality of life of seniors.

  18. Comparison of molecular breeding values based on within- and across-breed training in beef cattle

    PubMed Central

    2013-01-01

    Background Although the efficacy of genomic predictors based on within-breed training looks promising, it is necessary to develop and evaluate across-breed predictors for the technology to be fully applied in the beef industry. The efficacies of genomic predictors trained in one breed and utilized to predict genetic merit in differing breeds based on simulation studies have been reported, as have the efficacies of predictors trained using data from multiple breeds to predict the genetic merit of purebreds. However, comparable studies using beef cattle field data have not been reported. Methods Molecular breeding values for weaning and yearling weight were derived and evaluated using a database containing BovineSNP50 genotypes for 7294 animals from 13 breeds in the training set and 2277 animals from seven breeds (Angus, Red Angus, Hereford, Charolais, Gelbvieh, Limousin, and Simmental) in the evaluation set. Six single-breed and four across-breed genomic predictors were trained using pooled data from purebred animals. Molecular breeding values were evaluated using field data, including genotypes for 2227 animals and phenotypic records of animals born in 2008 or later. Accuracies of molecular breeding values were estimated based on the genetic correlation between the molecular breeding value and trait phenotype. Results With one exception, the estimated genetic correlations of within-breed molecular breeding values with trait phenotype were greater than 0.28 when evaluated in the breed used for training. Most estimated genetic correlations for the across-breed trained molecular breeding values were moderate (> 0.30). When molecular breeding values were evaluated in breeds that were not in the training set, estimated genetic correlations clustered around zero. Conclusions Even for closely related breeds, within- or across-breed trained molecular breeding values have limited prediction accuracy for breeds that were not in the training set. For breeds in the training

  19. Fast parallel molecular algorithms for DNA-based computation: factoring integers.

    PubMed

    Chang, Weng-Long; Guo, Minyi; Ho, Michael Shan-Hui

    2005-06-01

    The RSA public-key cryptosystem is an algorithm that converts input data to an unrecognizable encryption and converts the unrecognizable data back into its original decryption form. The security of the RSA public-key cryptosystem is based on the difficulty of factoring the product of two large prime numbers. This paper demonstrates to factor the product of two large prime numbers, and is a breakthrough in basic biological operations using a molecular computer. In order to achieve this, we propose three DNA-based algorithms for parallel subtractor, parallel comparator, and parallel modular arithmetic that formally verify our designed molecular solutions for factoring the product of two large prime numbers. Furthermore, this work indicates that the cryptosystems using public-key are perhaps insecure and also presents clear evidence of the ability of molecular computing to perform complicated mathematical operations.

  20. Giant tunnel magneto-resistance in graphene based molecular tunneling junction

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Li, Jianwei; Yu, Yunjin; Wei, Yadong; Wang, Jian; Guo, Hong

    2016-02-01

    We propose and theoretically investigate a class of stable zigzag graphene nanoribbon (ZGNR) based molecular magnetic tunneling junctions (MTJs). For those junctions having pentagon-connecting formations, huge tunnel magneto-resistance (TMR) is found. Different from most of the other proposed molecular junctions, the huge TMR in our structures is generic, and is not significantly affected by external parameters such as bias voltage, gate voltage, length of the molecule and width of the ZGNRs. The double pentagon-connecting formation between the molecule and ZGNRs is critical for the remarkable TMR ratio, which is as large as ~2 × 105. These molecular MTJs behave as almost perfect spin filters and spin valve devices. Other connecting formations of the ZGNR based MTJs lead to much smaller TMR. By first principles analysis, we reveal the microscopic physics responsible for this phenomenon.

  1. Giant tunnel magneto-resistance in graphene based molecular tunneling junction.

    PubMed

    Wang, Bin; Li, Jianwei; Yu, Yunjin; Wei, Yadong; Wang, Jian; Guo, Hong

    2016-02-14

    We propose and theoretically investigate a class of stable zigzag graphene nanoribbon (ZGNR) based molecular magnetic tunneling junctions (MTJs). For those junctions having pentagon-connecting formations, huge tunnel magneto-resistance (TMR) is found. Different from most of the other proposed molecular junctions, the huge TMR in our structures is generic, and is not significantly affected by external parameters such as bias voltage, gate voltage, length of the molecule and width of the ZGNRs. The double pentagon-connecting formation between the molecule and ZGNRs is critical for the remarkable TMR ratio, which is as large as ∼2 × 10(5). These molecular MTJs behave as almost perfect spin filters and spin valve devices. Other connecting formations of the ZGNR based MTJs lead to much smaller TMR. By first principles analysis, we reveal the microscopic physics responsible for this phenomenon. PMID:26790615

  2. Detection of airborne bacteria in a German turkey house by cultivation-based and molecular methods.

    PubMed

    Fallschissel, Kerstin; Klug, Kerstin; Kämpfer, Peter; Jäckel, Udo

    2010-11-01

    Today's large-scale poultry production with densely stocked and enclosed production buildings is often accompanied by very high concentrations of airborne microorganisms leading to a clear health hazard for employees working in such environments. Depending on the expected exposure to microorganisms, work has to be performed under occupational safety conditions. In this study, turkey houses bioaerosols were investigated by cultivation-based and molecular methods in parallel to determine the concentrations and the composition of bacterial community. Results obtained with the molecular approach showed clearly its applicability for qualitative exposure measurements. With both, cultivation-based and molecular methods species of microorganism with a potential health risk for employees (Acinetobacter johnsonii, Aerococcus viridans, Pantoea agglomerans, and Shigella flexneri) were identified. These results underline the necessity of adequate protection measures, including the recommendation to wear breathing masks during work in poultry houses.

  3. Feasibility of using molecular docking-based virtual screening for searching dual target kinase inhibitors.

    PubMed

    Zhou, Shunye; Li, Youyong; Hou, Tingjun

    2013-04-22

    Multitarget agents have been extensively explored for solving limited efficacies, poor safety, and resistant profiles of an individual target. Theoretical approaches for searching and designing multitarget agents are critically useful. Here, the performance of molecular docking to search dual-target inhibitors for four kinase pairs (CDK2-GSK3B, EGFR-Src, Lck-Src, and Lck-VEGFR2) was assessed. First, the representative structures for each kinase target were chosen by structural clustering of available crystal structures. Next, the performance of molecular docking to distinguish inhibitors from noninhibitors for each individual kinase target was evaluated. The results show that molecular docking-based virtual screening illustrates good capability to find known inhibitors for individual targets, but the prediction accuracy is structurally dependent. Finally, the performance of molecular docking to identify the dual-target kinase inhibitors for four kinase pairs was evaluated. The analyses show that molecular docking successfully filters out most noninhibitors and achieves promising performance for identifying dual-kinase inhibitors for CDK2-GSK3B and Lck-VEGFR2. But a high false-positive rate leads to low enrichment of true dual-target inhibitors in the final list. This study suggests that molecular docking serves as a useful tool in searching inhibitors against dual or even multiple kinase targets, but integration with other virtual screening tools is necessary for achieving better predictions.

  4. Double-hairpin molecular-beacon-based amplification detection for gene diagnosis linked to cancer.

    PubMed

    Xu, Huo; Zhang, Rongbo; Li, Feng; Zhou, Yingying; Peng, Ting; Wang, Xuedong; Shen, Zhifa

    2016-09-01

    A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related KRAS gene detection based on the one-to-two stoichiometry. During target DNA detection, DHMB can execute signal transduction even if no any exogenous element is involved. Unlike the conventional molecular beacon based on the one-to-one interaction, one target DNA not only hybridizes with one DHMB and opens its hairpin but also promotes the interaction between two DHMBs, causing the separation of two fluorophores from quenchers. This leads to an enhanced fluorescence signal. As a result, the target KRAS gene is able to be detected within a wide dynamic range from 0.05 to 200 nM with the detection limit of 50 pM, indicating a dramatic improvement compared with traditional molecular beacons. Moreover, the point mutations existing in target DNAs can be easily screened. The potential application for target species in real samples was indicated by the analysis of PCR amplicons of DNAs from the DNA extracted from SW620 cell. Besides becoming a promising candidate probe for molecular biology research and clinical diagnosis of genetic diseases, the DHMB is expected to provide a significant insight into the design of DNA probe-based homogenous sensing systems. Graphical Abstract A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related gene KRAS detection based on the one-to-two stoichiometry. Without the help of any exogenous probe, the point mutation is easily screened, and the target DNA can be quantified down to 50 pM, indicating a dramatic improvement compared with traditional molecular beacons. PMID:27422649

  5. Double-hairpin molecular-beacon-based amplification detection for gene diagnosis linked to cancer.

    PubMed

    Xu, Huo; Zhang, Rongbo; Li, Feng; Zhou, Yingying; Peng, Ting; Wang, Xuedong; Shen, Zhifa

    2016-09-01

    A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related KRAS gene detection based on the one-to-two stoichiometry. During target DNA detection, DHMB can execute signal transduction even if no any exogenous element is involved. Unlike the conventional molecular beacon based on the one-to-one interaction, one target DNA not only hybridizes with one DHMB and opens its hairpin but also promotes the interaction between two DHMBs, causing the separation of two fluorophores from quenchers. This leads to an enhanced fluorescence signal. As a result, the target KRAS gene is able to be detected within a wide dynamic range from 0.05 to 200 nM with the detection limit of 50 pM, indicating a dramatic improvement compared with traditional molecular beacons. Moreover, the point mutations existing in target DNAs can be easily screened. The potential application for target species in real samples was indicated by the analysis of PCR amplicons of DNAs from the DNA extracted from SW620 cell. Besides becoming a promising candidate probe for molecular biology research and clinical diagnosis of genetic diseases, the DHMB is expected to provide a significant insight into the design of DNA probe-based homogenous sensing systems. Graphical Abstract A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related gene KRAS detection based on the one-to-two stoichiometry. Without the help of any exogenous probe, the point mutation is easily screened, and the target DNA can be quantified down to 50 pM, indicating a dramatic improvement compared with traditional molecular beacons.

  6. Ultrasound-based Measurement of Molecular Marker Concentration in Large Blood Vessels: A Feasibility Study

    PubMed Central

    Wang, Shiying; Mauldin, F. William; Klibanov, Alexander L.; Hossack, John A.

    2014-01-01

    Ultrasound molecular imaging has demonstrated efficacy in pre-clinical studies for cancer and cardiovascular inflammation. However, these techniques often require lengthy protocols due to waiting periods or additional control microbubble injections. Moreover, they are not capable of quantifying molecular marker concentration in human tissue environments that exhibit variable attenuation and propagation path lengths. Our group recently investigated a modulated Acoustic Radiation Force (ARF)-based imaging sequence, which was demonstrated to detect targeted adhesion independent of control measurements. In the present study, this sequence was tested against various experimental parameters to determine feasibility for quantitative measurements of molecular marker concentration. Results demonstrated that measurements obtained from the sequence (residual-to-saturation ratio, Rresid) were independent of acoustic pressure and attenuation (p> 0.13, n = 10)when acoustic pressures were sufficiently low. The Rresid parameter exhibited a linear relationship with measured molecular marker concentration (R2> 0.94). Consequently, feasibility was demonstrated in vitro, for quantification of molecular marker concentration in large vessels using a modulated ARF-based sequence. Moreover, these measurements were independent of absolute acoustic reflection amplitude and used short imaging protocols(3 min) without control measurements. PMID:25308943

  7. Base de linhas moleculares para síntese espectral estelar

    NASA Astrophysics Data System (ADS)

    Milone, A.; Sanzovo, G.

    2003-08-01

    A análise das abundâncias quí micas fotosféricas em estrelas do tipo solar ou tardia, através do cálculo teórico de seus espectros, emprega a espectroscopia de alta resolução e necessita de uma base representativa de linhas atômicas e moleculares com suas respectivas constantes bem determinadas. Nesse trabalho, utilizamos como ponto de partida as extensas listas de linhas espectrais de sistemas eletrônicos de algumas moléculas diatômicas compiladas por Kurucz para a construção de uma base de linhas moleculares para a sí ntese espectral estelar. Revisamos as determinações dos fatores rotacionais de Honl-London das forças de oscilador das linhas moleculares, para cada banda vibracional de alguns sistemas eletrônicos, seguindo a regra usual de normalização. Usamos as forças de oscilador eletrônicas da literatura. Os fatores vibracionais de Franck-Condon de cada banda foram especialmente recalculados empregando-se novas constantes moleculares. Reproduzimos, com êxito, as absorções espectrais de determinadas bandas eletrônicas-vibracionais das espécies moleculares C12C12, C12N14 e Mg24H em espectros de estrelas de referência como o Sol e Arcturus.

  8. Fragment-Based Electronic Structure Approach for Computing Nuclear Magnetic Resonance Chemical Shifts in Molecular Crystals.

    PubMed

    Hartman, Joshua D; Beran, Gregory J O

    2014-11-11

    First-principles chemical shielding tensor predictions play a critical role in studying molecular crystal structures using nuclear magnetic resonance. Fragment-based electronic structure methods have dramatically improved the ability to model molecular crystal structures and energetics using high-level electronic structure methods. Here, a many-body expansion fragment approach is applied to the calculation of chemical shielding tensors in molecular crystals. First, the impact of truncating the many-body expansion at different orders and the role of electrostatic embedding are examined on a series of molecular clusters extracted from molecular crystals. Second, the ability of these techniques to assign three polymorphic forms of the drug sulfanilamide to the corresponding experimental (13)C spectra is assessed. This challenging example requires discriminating among spectra whose (13)C chemical shifts differ by only a few parts per million (ppm) across the different polymorphs. Fragment-based PBE0/6-311+G(2d,p) level chemical shielding predictions correctly assign these three polymorphs and reproduce the sulfanilamide experimental (13)C chemical shifts with 1 ppm accuracy. The results demonstrate that fragment approaches are competitive with the widely used gauge-invariant projector augmented wave (GIPAW) periodic density functional theory calculations. PMID:26584373

  9. Ultrasound-based measurement of molecular marker concentration in large blood vessels: a feasibility study.

    PubMed

    Wang, Shiying; Mauldin, F William; Klibanov, Alexander L; Hossack, John A

    2015-01-01

    Ultrasound molecular imaging has demonstrated efficacy in pre-clinical studies for cancer and cardiovascular inflammation. However, these techniques often require lengthy protocols because of waiting periods or additional control microbubble injections. Moreover, they are not capable of quantifying molecular marker concentration in human tissue environments that exhibit variable attenuation and propagation path lengths. Our group recently investigated a modulated acoustic radiation force-based imaging sequence, which was found to detect targeted adhesion independent of control measurements. In the present study, this sequence was tested against various experimental parameters to determine its feasibility for quantitative measurements of molecular marker concentration. Results indicated that measurements obtained from the sequence (residual-to-saturation ratio, Rresid) were independent of acoustic pressure and attenuation (p > 0.13, n = 10) when acoustic pressures were sufficiently low. The Rresid parameter exhibited a linear relationship with measured molecular marker concentration (R(2) > 0.94). Consequently, feasibility was illustrated in vitro, for quantification of molecular marker concentration in large vessels using a modulated acoustic radiation force-based sequence. Moreover, these measurements were independent of absolute acoustic reflection amplitude and used short imaging protocols (3 min) without control measurements.

  10. Accelerated electronic structure-based molecular dynamics simulations of shock-induced chemistry

    NASA Astrophysics Data System (ADS)

    Cawkwell, Marc

    2015-06-01

    The initiation and progression of shock-induced chemistry in organic materials at moderate temperatures and pressures are slow on the time scales available to regular molecular dynamics simulations. Accessing the requisite time scales is particularly challenging if the interatomic bonding is modeled using accurate yet expensive methods based explicitly on electronic structure. We have combined fast, energy conserving extended Lagrangian Born-Oppenheimer molecular dynamics with the parallel replica accelerated molecular dynamics formalism to study the relatively sluggish shock-induced chemistry of benzene around 13-20 GPa. We model interatomic bonding in hydrocarbons using self-consistent tight binding theory with an accurate and transferable parameterization. Shock compression and its associated transient, non-equilibrium effects are captured explicitly by combining the universal liquid Hugoniot with a simple shrinking-cell boundary condition. A number of novel methods for improving the performance of reactive electronic structure-based molecular dynamics by adapting the self-consistent field procedure on-the-fly will also be discussed. The use of accelerated molecular dynamics has enabled us to follow the initial stages of the nucleation and growth of carbon clusters in benzene under thermodynamic conditions pertinent to experiments.

  11. Molecular Interactions between a Novel Soybean Oil-Based Polymer and Doxorubicin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel soybean oil-based polymer, hydrolyzed polymers of epoxidized soybean oil (HPESO), was developed and investigated for drug delivery. This work was aimed at determining the molecular interactions between HPESO and doxorubicin (DOX), an anticancer drug. Powder X-ray diffraction, ATR-FTIR and ...

  12. Protein-based fluorescent metal nanoclusters for small molecular drug screening.

    PubMed

    Yu, Yong; New, Siu Yee; Xie, Jianping; Su, Xiaodi; Tan, Yen Nee

    2014-11-18

    A facile drug screening method based on synthesis of fluorescent gold nanoclusters inside albumin proteins loaded with small molecular drugs and comparing the relative fluorescence intensities of the resultant gold nanoclusters has been developed and successfully applied for the quantitative measurement of drug-protein binding constants. PMID:25253537

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

    ERIC Educational Resources Information Center

    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…

  14. A versatile electrochemical sensing receptor based on a molecularly imprinted polymer.

    PubMed

    Udomsap, Dutduan; Branger, Catherine; Culioli, Gérald; Dollet, Pascal; Brisset, Hugues

    2014-07-18

    Electrochemical molecularly imprinted polymers (e-MIPs) are reported for the first time. Their elaboration is based on the introduction of a redox tracer (vinylferrocene) inside the binding cavities of a cross-linked MIP. Determination of the analyte (benzo[a]pyrene) can be simply performed by measuring the redox tracer signal.

  15. Molecular beacon-based half-adder and half-subtractor.

    PubMed

    Yang, Chia-Ning; Hsu, Chun-Yu; Chuang, Yu-Chung

    2012-01-01

    This work demonstrates two DNA-based logic circuits that behave as a half-adder and a half-subtractor. A half-adder is composed of an AND gate and an XOR gate, whereas a half-subtractor consists of an INH gate and an XOR gate. The proposed designs are inspired by molecular beacons.

  16. Designing and Implementing a Hands-On, Inquiry-Based Molecular Biology Course

    ERIC Educational Resources Information Center

    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…

  17. QSPR correlation of melting point for drug compounds based on different sources of molecular descriptors.

    PubMed

    Modarresi, Hassan; Dearden, John C; Modarress, Hamid

    2006-01-01

    Five linear QSPR models for melting points (MP) of drug-like compounds are developed based on three different packages for molecular descriptor generation and a combined set of all descriptors. A data set of 323 gaseous, liquid, and solid compounds was used for this study. Two models from the combined set of descriptors based on stepwise regression and genetic algorithm (GA) descriptor selection methods have acceptable prediction abilities. The statistical results of these models are r2 = 0.673 and root-mean-square error (RMSE) of 40.4 degrees C for stepwise regression-based quantitative structure-property relationships (QSPRs) and r2 = 0.660 and RMSE of 41.1 degrees C for GA-based QSPRs. Interpretation of descriptors of all models showed a strong correlation of hydrogen bonding and molecular complexity with melting points of drug-like compounds.

  18. Detection of DNA damage based on metal-mediated molecular beacon and DNA strands displacement reaction.

    PubMed

    Xiong, Yanxiang; Wei, Min; Wei, Wei; Yin, Lihong; Pu, Yuepu; Liu, Songqin

    2014-01-24

    DNA hairpin structure probes are usually designed by forming intra-molecular duplex based on Watson-Crick hydrogen bonds. In this paper, a molecular beacon based on silver ions-mediated cytosine-Ag(+)-cytosine base pairs was used to detect DNA. The inherent characteristic of the metal ligation facilitated the design of functional probe and the adjustment of its binding strength compared to traditional DNA hairpin structure probes, which make it be used to detect DNA in a simple, rapid and easy way with the help of DNA strands displacement reaction. The method was sensitive and also possesses the good specificity to differentiate the single base mismatched DNA from the complementary DNA. It was also successfully applied to study the damage effect of classic genotoxicity chemicals such as styrene oxide and sodium arsenite on DNA, which was significant in food science, environmental science and pharmaceutical science.

  19. Detection of DNA damage based on metal-mediated molecular beacon and DNA strands displacement reaction

    NASA Astrophysics Data System (ADS)

    Xiong, Yanxiang; Wei, Min; Wei, Wei; Yin, Lihong; Pu, Yuepu; Liu, Songqin

    2014-01-01

    DNA hairpin structure probes are usually designed by forming intra-molecular duplex based on Watson-Crick hydrogen bonds. In this paper, a molecular beacon based on silver ions-mediated cytosine-Ag+-cytosine base pairs was used to detect DNA. The inherent characteristic of the metal ligation facilitated the design of functional probe and the adjustment of its binding strength compared to traditional DNA hairpin structure probes, which make it be used to detect DNA in a simple, rapid and easy way with the help of DNA strands displacement reaction. The method was sensitive and also possesses the good specificity to differentiate the single base mismatched DNA from the complementary DNA. It was also successfully applied to study the damage effect of classic genotoxicity chemicals such as styrene oxide and sodium arsenite on DNA, which was significant in food science, environmental science and pharmaceutical science.

  20. Isatin based thiosemicarbazone derivatives as potential bioactive agents: Anti-oxidant and molecular docking studies

    NASA Astrophysics Data System (ADS)

    Haribabu, J.; Subhashree, G. R.; Saranya, S.; Gomathi, K.; Karvembu, R.; Gayathri, D.

    2016-04-01

    A new series of isatin based thiosemicarbazones has been synthesized from benzylisatin and unsubstituted/substituted thiosemicarbazides (1-5). The synthesized compounds were characterized by elemental analyses, and UV-Visible, FT-IR, 1H &13C NMR and mass spectroscopic techniques. Three dimensional molecular structure of three compounds (1, 3 and 4) was determined by single crystal X-ray crystallography. Anti-oxidant activity of the thiosemicarbazone derivatives showed their excellent scavenging effect against free radicals. In addition, all the compounds showed good anti-haemolytic activity. In silico molecular docking studies were performed to screen the anti-inflammatory and anti-tuberculosis properties of thiosemicarbazone derivatives.

  1. Nonadiabatic molecular dynamics simulation: An approach based on quantum measurement picture

    SciTech Connect

    Feng, Wei; Xu, Luting; Li, Xin-Qi; Fang, Weihai; Yan, YiJing

    2014-07-15

    Mixed-quantum-classical molecular dynamics simulation implies an effective quantum measurement on the electronic states by the classical motion of atoms. Based on this insight, we propose a quantum trajectory mean-field approach for nonadiabatic molecular dynamics simulations. The new protocol provides a natural interface between the separate quantum and classical treatments, without invoking artificial surface hopping algorithm. Moreover, it also bridges two widely adopted nonadiabatic dynamics methods, the Ehrenfest mean-field theory and the trajectory surface-hopping method. Excellent agreement with the exact results is illustrated with representative model systems, including the challenging ones for traditional methods.

  2. Ab initio based force field and molecular dynamics simulations of crystalline TATB.

    PubMed

    Gee, Richard H; Roszak, Szczepan; Balasubramanian, Krishnan; Fried, Laurence E

    2004-04-15

    An all-atom force field for 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is presented. The classical intermolecular interaction potential for TATB is based on single-point energies determined from high-level ab initio calculations of TATB dimers. The newly developed potential function is used to examine bulk crystalline TATB via molecular dynamics simulations. The isobaric thermal expansion and isothermal compression under hydrostatic pressures obtained from the molecular dynamics simulations are in good agreement with experiment. The calculated volume-temperature expansion is almost one dimensional along the c crystallographic axis, whereas under compression, all three unit cell axes participate, albeit unequally. PMID:15267608

  3. Molecular evidence-based medicine: evolution and integration of information in the genomic era.

    PubMed

    Ioannidis, J P A

    2007-05-01

    Evidence-based medicine and molecular medicine have both been influential in biomedical research in the last 15 years. Despite following largely parallel routes to date, the goals and principles of evidence-based and molecular medicine are complementary and they should be converging. I define molecular evidence-based medicine as the study of medical information that makes sense of the advances of molecular biological disciplines and where errors and biases are properly appreciated and placed in context. Biomedical measurement capacity improves very rapidly. The exponentially growing mass of hypotheses being tested requires a new approach to both statistical and biological inference. Multidimensional biology requires careful exact replication of research findings, but indirect corroboration is often all that is achieved at best. Besides random error, bias remains a major threat. It is often difficult to separate bias from the spirit of scientific inquiry to force data into coherent and 'significant' biological stories. Transparency and public availability of protocols, data, analyses and results may be crucial to make sense of the complex biology of human disease and avoid being flooded by spurious research findings. Research efforts should be integrated across teams in an open, sharing environment. Most research in the future may be designed, performed, and integrated in the public cyberspace. PMID:17461979

  4. Integration of Culture-Based and Molecular Analysis of a Complex Sponge-Associated Bacterial Community

    PubMed Central

    Vicente, Jan; Pittiglio, Raquel; Ravel, Jacques; Hill, Russell T.

    2014-01-01

    The bacterial communities of sponges have been studied using molecular techniques as well as culture-based techniques, but the communities described by these two methods are remarkably distinct. Culture-based methods describe communities dominated by Proteobacteria, and Actinomycetes while molecular methods describe communities dominated by predominantly uncultivated groups such as the Chloroflexi, Acidobacteria, and Acidimicrobidae. In this study, we used a wide range of culture media to increase the diversity of cultivable bacteria from the closely related giant barrel sponges, Xestospongia muta collected from the Florida Keys, Atlantic Ocean and Xestospongia testudinaria, collected from Indonesia, Pacific Ocean. Over 400 pure cultures were isolated and identified from X. muta and X. testudinaria and over 90 bacterial species were represented. Over 16,000 pyrosequences were analyzed and assigned to 976 OTUs. We employed both cultured-based methods and pyrosequencing to look for patterns of overlap between the culturable and molecular communities. Only one OTU was found in both the molecular and culturable communities, revealing limitations inherent in both approaches. PMID:24618773

  5. High-molecular-weight polymers for protein crystallization: poly-gamma-glutamic acid-based precipitants.

    PubMed

    Hu, Ting Chou; Korczyńska, Justyna; Smith, David K; Brzozowski, Andrzej Marek

    2008-09-01

    Protein crystallization has been revolutionized by the introduction of high-throughput technologies, which have led to a speeding up of the process while simultaneously reducing the amount of protein sample necessary. Nonetheless, the chemistry dimension of protein crystallization has remained relatively undeveloped. Most crystallization screens are based on the same set of precipitants. To address this shortcoming, the development of new protein precipitants based on poly-gamma-glutamic acid (PGA) polymers with different molecular-weight ranges is reported here: PGA-LM (low molecular weight) of approximately 400 kDa and PGA-HM (high molecular weight) of >1,000 kDa. It is also demonstrated that protein precipitants can be expanded further to polymers with much higher molecular weight than those that are currently in use. Furthermore, the modification of PGA-like polymers by covalent attachments of glucosamine substantially improved their solubility without affecting their crystallization properties. Some preliminary PGA-based screens are presented here.

  6. Towards artificial molecular motor-based electroactive/photoactive biomimetic muscles

    NASA Astrophysics Data System (ADS)

    Huang, Tony Jun

    2007-04-01

    Artificial molecular motors have recently attracted considerable interest from the nanoscience and nanoengineering community. These molecular-scale systems utilize a 'bottom-up' technology centered around the design and manipulation of molecular assemblies, and are potentially capable of delivering efficient actuations at dramatically reduced length scales when compared to traditional microscale actuators. When stimulated by light, electricity, or chemical reagents, a group of artificial molecular motors called bistable rotaxanes - which are composed of mutually recognizable and intercommunicating ring and dumbbell-shaped components - experience relative internal motions of their components just like the moving parts of macroscopic machines. Bistable rotaxanes' ability to precisely and cooperatively control mechanical motions at the molecular level reveals the potential of engineering systems that operate with the same elegance, efficiency, and complexity as biological motors function within the human body. We are in a process of developing a new class of bistable rotaxane-based electroactive/photoactive biomimetic muscles with unprecedented performance (strain: 40-60%, operating frequency: up to 1 MHz, energy density: ~50 J/cm 3, multi-stimuli: chemical, electricity, light). As a substantial step towards this longterm objective, we have proven, for the first time, that rotaxanes are mechanically switchable in condensed phases on solid substrates. We have further developed a rotaxane-powered microcantilever actuator utilizing an integrated approach that combines "bottom-up" assembly of molecular functionality with "top-down" micro/nano fabrication. By harnessing the nanoscale mechanical motion from artificial molecular machines and eliciting a nanomechanical response in a microscale device, this system mimics natural skeletal muscle and provides a key component for the development of nanoelectromechanical system (NEMS).

  7. Fibrin-based biomaterials: Modulation of macroscopic properties through rational design at the molecular level

    PubMed Central

    Brown, Ashley C.; Barker, Thomas H.

    2013-01-01

    Fibrinogen is one of the primary components of the coagulation cascade and rapidly forms an insoluble matrix following tissue injury. In addition to its important role in hemostasis, fibrin acts as a scaffold for tissue repair and provides important cues for directing cell phenotype following injury. Because of these properties and the ease of polymerization of the material, fibrin has been widely utilized as a biomaterial for over a century. Modifying the macroscopic properties of fibrin, such as elasticity and porosity, has been somewhat elusive until recently, yet with a molecular-level rational design approach can now be somewhat easily modified through alterations of molecular interactions key to the protein’s polymerization process. This review outlines the biochemistry of fibrin and discusses methods for modification of molecular interactions and their application to fibrin based biomaterials. PMID:24056097

  8. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    PubMed

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  9. An Electrically Driven and Readable Molecular Monolayer Switch Based on a Solid Electrolyte.

    PubMed

    Marchante, Elena; Crivillers, Núria; Buhl, Moritz; Veciana, Jaume; Mas-Torrent, Marta

    2016-01-01

    The potential application of molecular switches as active elements in information storage has been demonstrated through numerous works. Importantly, such switching capabilities have also been reported for self-assembled monolayers (SAMs). SAMs of electroactive molecules have recently been exploited as electrochemical switches. Typically, the state of these switches could be read out through their optical and/or magnetic response. These output reading processes are difficult to integrate into devices, and furthermore, there is a need to use liquid environments for switching the redox-active molecular systems. In this work, both of these challenges were overcome by using an ionic gel as the electrolyte medium, which led to an unprecedented solid-state device based on a single molecular layer. Moreover, electrochemical impedance has been successfully exploited as the output of the system.

  10. Realizing tunable molecular thermal devices based on photoisomerism—Is it possible?

    SciTech Connect

    Ranganathan, Raghavan; Sasikumar, Kiran; Keblinski, Pawel

    2015-01-14

    In this work, we address the question if it is possible to tune the thermal conductance through photoisomerism-capable molecular junctions. Using non-equilibrium molecular dynamics simulations, we study heat flow due to phonons between two silicon leads connected via two classes of photoisomeric molecules—(a) azobenzene and (b) Spiropyran (SP)–Merocyanine (MC) isomers. For the case of azobenzene, isomeric states with different conformations are realized via mechanical strain, while in the case of SP-MC, via a hybridization change. Based on the phononic contribution to thermal conductance, we observe that the thermal conductance of both junctions is rather insensitive to the isomeric state, thereby rendering the tunability of molecular thermal devices rather difficult. Consistent with these observations, the vibrational density of states for different configurations yields very similar spectra. We note that including the effect of electronic contribution to thermal conductance could enhance the tunability of thermal properties, albeit weakly.

  11. Interference between concurrent resistance and endurance exercise: molecular bases and the role of individual training variables.

    PubMed

    Fyfe, Jackson J; Bishop, David J; Stepto, Nigel K

    2014-06-01

    Concurrent training is defined as simultaneously incorporating both resistance and endurance exercise within a periodized training regime. Despite the potential additive benefits of combining these divergent exercise modes with regards to disease prevention and athletic performance, current evidence suggests that this approach may attenuate gains in muscle mass, strength, and power compared with undertaking resistance training alone. This has been variously described as the interference effect or concurrent training effect. In recent years, understanding of the molecular mechanisms mediating training adaptation in skeletal muscle has emerged and provided potential mechanistic insight into the concurrent training effect. Although it appears that various molecular signaling responses induced in skeletal muscle by endurance exercise can inhibit pathways regulating protein synthesis and stimulate protein breakdown, human studies to date have not observed such molecular 'interference' following acute concurrent exercise that might explain compromised muscle hypertrophy following concurrent training. However, given the multitude of potential concurrent training variables and the limitations of existing evidence, the potential roles of individual training variables in acute and chronic interference are not fully elucidated. The present review explores current evidence for the molecular basis of the specificity of training adaptation and the concurrent interference phenomenon. Additionally, insights provided by molecular and performance-based concurrent training studies regarding the role of individual training variables (i.e., within-session exercise order, between-mode recovery, endurance training volume, intensity, and modality) in the concurrent interference effect are discussed, along with the limitations of our current understanding of this complex paradigm.

  12. Simple and universal platform for logic gate operations based on molecular beacon probes.

    PubMed

    Park, Ki Soo; Seo, Myung Wan; Jung, Cheulhee; Lee, Joon Young; Park, Hyun Gyu

    2012-07-23

    A new platform technology is herein described with which to construct molecular logic gates by employing the hairpin-structured molecular beacon probe as a basic work unit. In this logic gate operation system, single-stranded DNA is used as the input to induce a conformational change in a molecular beacon probe through a sequence-specific interaction. The fluorescent signal resulting from the opening of the molecular beacon probe is then used as the output readout. Importantly, because the logic gates are based on DNA, thus permitting input/output homogeneity to be preserved, their wiring into multi-level circuits can be achieved by combining separately operated logic gates or by designing the DNA output of one gate as the input to the other. With this novel strategy, a complete set of two-input logic gates is successfully constructed at the molecular level, including OR, AND, XOR, INHIBIT, NOR, NAND, XNOR, and IMPLICATION. The logic gates developed herein can be reversibly operated to perform the set-reset function by applying an additional input or a removal strand. Together, these results introduce a new platform technology for logic gate operation that enables the higher-order circuits required for complex communication between various computational elements.

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

    PubMed

    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. PMID:25937012

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

    PubMed

    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.

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

    PubMed

    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

  16. A tetraphenylethylene core-based 3D structure small molecular acceptor enabling efficient non-fullerene organic solar cells.

    PubMed

    Liu, Yuhang; Mu, Cheng; Jiang, Kui; Zhao, Jingbo; Li, Yunke; Zhang, Lu; Li, Zhengke; Lai, Joshua Yuk Lin; Hu, Huawei; Ma, Tingxuan; Hu, Rongrong; Yu, Demei; Huang, Xuhui; Tang, Ben Zhong; Yan, He

    2015-02-01

    A tetraphenylethylene core-based small molecular acceptor with a unique 3D molecular structure is developed. Bulk-heterojunction blend films with a small feature size (≈20 nm) are obtained, which lead to non-fullerene organic solar cells (OSCs) with 5.5% power conversion efficiency. The work provides a new molecular design approach to efficient non-fullerene OSCs based on 3D-structured small-molecule acceptors.

  17. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    PubMed Central

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  18. PC-based molecular modeling in the classroom: applications to medicinal chemistry and biochemistry.

    PubMed

    Henkel, J G

    1991-03-01

    Among the most difficult aspects of medicinal chemistry and biochemistry for the student to master are the three-dimensional (3D) nature of drugs and bio-organic substances and the interaction of these substances with 3D targets. Compounding this problem is the fact that such relationships are very difficult to illustrate in a lecture or discussion format. While skeletal molecular models serve a useful role in the learning process, the techniques of PC-based desktop molecular visualization provide a more powerful and effective alternative to the lecture format. These techniques can be implemented on standard MS-DOS PC hardware using one of the commonly available data projection systems. The approach has found considerable use in several areas, including the generation of computer-based lecture aids, the illustration of the molecular shapes of drugs and biochemical structures, the superposition and comparison of drug substances with common pharmacophores, and the illustration of enzyme-substrate interactions. Another related technique, molecular animation, has proven to be quite successful at illustrating the essentials of enzyme mechanisms in the classroom. The "film clips" resulting from this technique may have use beyond the classroom, and further work in this area is underway.

  19. Identification of a novel V1-type AVP receptor based on the molecular recognition theory.

    PubMed Central

    Herrera, V. L.; Ruiz-Opazo, N.

    2001-01-01

    BACKGROUND: The molecular recognition theory predicts that binding domains of peptide hormones and their corresponding receptor binding domains evolved from complementary strands of genomic DNA, and that a process of selective evolutionary mutational events within these primordial domains gave rise to the high affinity and high specificity of peptide hormone-receptor interactions observed today in different peptide hormone-receptor systems. Moreover, this theory has been broadened as a general hypothesis that could explain the evolution of intermolecular protein-protein and intramolecular peptide interactions. MATERIALS AND METHODS: Applying a molecular cloning strategy based on the molecular recognition theory, we screened a rat kidney cDNA library with a vasopressin (AVP) antisense oligonucleotide probe, expecting to isolate potential AVP receptors. RESULTS: We isolated a rat kidney cDNA encoding a functional V1-type vasopressin receptor. Structural analysis identified a 135 amino acid-long polypeptide with a single transmembrane domain, quite distinct from the rhodopsin-based G protein-coupled receptor superfamily. Functional analysis of the expressed V1-type receptor in Cos-1 cells revealed AVP-specific binding, AVP-specific coupling to Ca2+ mobilizing transduction system, and characteristic V1-type antagonist inhibition. CONCLUSIONS: This is the second AVP receptor cDNA isolated using AVP antipeptide-based oligonucleotide screening, thus providing compelling evidence in support of the molecular recognition theory as the basis of the evolution of this peptide hormone-receptor system, as well as adds molecular complexity and diversity to AVP receptor systems. PMID:11683375

  20. Molecular sexing of birds: A comparative review of polymerase chain reaction (PCR)-based methods.

    PubMed

    Morinha, F; Cabral, J A; Bastos, E

    2012-09-01

    Accurate identification of sex in birds is important for the management and conservation of avian wildlife in several ways, namely in the development of population, behavioral and ecological studies, as well as in the improvement of ex situ captive breeding programs. In general, nestlings, juveniles and adult birds of a wide number of sexually monomorphic species cannot be sexed based on phenotypic traits. The development of molecular methodologies for avian sexing overcame these difficulties, allowing a reliable gender differentiation for these species. The polymerase chain reaction (PCR)-based methods have been widely applied in molecular sexing of birds, using a large diversity of sex-linked markers. During the last 15 yrs, there was a continuous improvement in the PCR-based protocols for bird sexing, increasing the accuracy, speed and high-throughput applicability of these techniques. The recent advances in real-time PCR platforms and whole genome analysis methods provided new resources for the detection and analysis of novel specific markers and protocols. This review presents a comparative guide of classical and recent advances in PCR-based methods for avian molecular sexing, highlighting its strengths and limitations. Future research opportunities in this field are also addressed.

  1. Molecular analysis of single oocyst of Eimeria by whole genome amplification (WGA) based nested PCR.

    PubMed

    Wang, Yunzhou; Tao, Geru; Cui, Yujuan; Lv, Qiyao; Xie, Li; Li, Yuan; Suo, Xun; Qin, Yinghe; Xiao, Lihua; Liu, Xianyong

    2014-09-01

    PCR-based molecular tools are widely used for the identification and characterization of protozoa. Here we report the molecular analysis of Eimeria species using combined methods of whole genome amplification (WGA) and nested PCR. Single oocyst of Eimeria stiedai or Eimeriamedia was directly used for random amplification of the genomic DNA with either primer extension preamplification (PEP) or multiple displacement amplification (MDA), and then the WGA product was used as template in nested PCR with species-specific primers for ITS-1, 18S rDNA and 23S rDNA of E. stiedai and E. media. WGA-based PCR was successful for the amplification of these genes from single oocyst. For the species identification of single oocyst isolated from mixed E. stiedai or E. media, the results from WGA-based PCR were exactly in accordance with those from morphological identification, suggesting the availability of this method in molecular analysis of eimerian parasites at the single oocyst level. WGA-based PCR method can also be applied for the identification and genetic characterization of other protists.

  2. Integrated biophysical studies implicate partial unfolding of NBD1 of CFTR in the molecular pathogenesis of F508del cystic fibrosis

    PubMed Central

    Wang, Chi; Protasevich, Irina; Yang, Zhengrong; Seehausen, Derek; Skalak, Timothy; Zhao, Xun; Atwell, Shane; Spencer Emtage, J; Wetmore, Diana R; Brouillette, Christie G; Hunt, John F

    2010-01-01

    The lethal genetic disease cystic fibrosis is caused predominantly by in-frame deletion of phenylalanine 508 in the cystic fibrosis transmembrane conductance regulator (CFTR). F508 is located in the first nucleotide-binding domain (NBD1) of CFTR, which functions as an ATP-gated chloride channel on the cell surface. The F508del mutation blocks CFTR export to the surface due to aberrant retention in the endoplasmic reticulum. While it was assumed that F508del interferes with NBD1 folding, biophysical studies of purified NBD1 have given conflicting results concerning the mutation's influence on domain folding and stability. We have conducted isothermal (this paper) and thermal (accompanying paper) denaturation studies of human NBD1 using a variety of biophysical techniques, including simultaneous circular dichroism, intrinsic fluorescence, and static light-scattering measurements. These studies show that, in the absence of ATP, NBD1 unfolds via two sequential conformational transitions. The first, which is strongly influenced by F508del, involves partial unfolding and leads to aggregation accompanied by an increase in tryptophan fluorescence. The second, which is not significantly influenced by F508del, involves full unfolding of NBD1. Mg-ATP binding delays the first transition, thereby offsetting the effect of F508del on domain stability. Evidence suggests that the initial partial unfolding transition is partially responsible for the poor in vitro solubility of human NBD1. Second-site mutations that increase the solubility of isolated F508del-NBD1 in vitro and suppress the trafficking defect of intact F508del-CFTR in vivo also stabilize the protein against this transition, supporting the hypothesize that it is responsible for the pathological trafficking of F508del-CFTR. PMID:20687163

  3. Charge transport and rectification in molecular junctions formed with carbon-based electrodes.

    PubMed

    Kim, Taekyeong; Liu, Zhen-Fei; Lee, Chulho; Neaton, Jeffrey B; Venkataraman, Latha

    2014-07-29

    Molecular junctions formed using the scanning-tunneling-microscope-based break-junction technique (STM-BJ) have provided unique insight into charge transport at the nanoscale. In most prior work, the same metal, typically Au, Pt, or Ag, is used for both tip and substrate. For such noble metal electrodes, the density of electronic states is approximately constant within a narrow energy window relevant to charge transport. Here, we form molecular junctions using the STM-BJ technique, with an Au metal tip and a microfabricated graphite substrate, and measure the conductance of a series of graphite/amine-terminated oligophenyl/Au molecular junctions. The remarkable mechanical strength of graphite and the single-crystal properties of our substrates allow measurements over few thousand junctions without any change in the surface properties. We show that conductance decays exponentially with molecular backbone length with a decay constant that is essentially the same as that for measurements with two Au electrodes. More importantly, despite the inherent symmetry of the oligophenylamines, we observe rectification in these junctions. State-of-art ab initio conductance calculations are in good agreement with experiment, and explain the rectification. We show that the highly energy-dependent graphite density of states contributes variations in transmission that, when coupled with an asymmetric voltage drop across the junction, leads to the observed rectification. Together, our measurements and calculations show how functionality may emerge from hybrid molecular-scale devices purposefully designed with different electrodes beyond the so-called "wide band limit," opening up the possibility of assembling molecular junctions with dissimilar electrodes using layered 2D materials.

  4. Charge transport and rectification in molecular junctions formed with carbon-based electrodes

    PubMed Central

    Kim, Taekyeong; Liu, Zhen-Fei; Lee, Chulho; Neaton, Jeffrey B.; Venkataraman, Latha

    2014-01-01

    Molecular junctions formed using the scanning-tunneling-microscope–based break-junction technique (STM-BJ) have provided unique insight into charge transport at the nanoscale. In most prior work, the same metal, typically Au, Pt, or Ag, is used for both tip and substrate. For such noble metal electrodes, the density of electronic states is approximately constant within a narrow energy window relevant to charge transport. Here, we form molecular junctions using the STM-BJ technique, with an Au metal tip and a microfabricated graphite substrate, and measure the conductance of a series of graphite/amine-terminated oligophenyl/Au molecular junctions. The remarkable mechanical strength of graphite and the single-crystal properties of our substrates allow measurements over few thousand junctions without any change in the surface properties. We show that conductance decays exponentially with molecular backbone length with a decay constant that is essentially the same as that for measurements with two Au electrodes. More importantly, despite the inherent symmetry of the oligophenylamines, we observe rectification in these junctions. State-of-art ab initio conductance calculations are in good agreement with experiment, and explain the rectification. We show that the highly energy-dependent graphite density of states contributes variations in transmission that, when coupled with an asymmetric voltage drop across the junction, leads to the observed rectification. Together, our measurements and calculations show how functionality may emerge from hybrid molecular-scale devices purposefully designed with different electrodes beyond the so-called “wide band limit,” opening up the possibility of assembling molecular junctions with dissimilar electrodes using layered 2D materials. PMID:25024198

  5. [Molecular genetic bases of adaptation processes and approaches to their analysis].

    PubMed

    Salmenkova, E A

    2013-01-01

    Great interest in studying the molecular genetic bases of the adaptation processes is explained by their importance in understanding evolutionary changes, in the development ofintraspecific and interspecific genetic diversity, and in the creation of approaches and programs for maintaining and restoring the population. The article examines the sources and conditions for generating adaptive genetic variability and contribution of neutral and adaptive genetic variability to the population structure of the species; methods for identifying the adaptive genetic variability on the genome level are also described. Considerable attention is paid to the potential of new technologies of genome analysis, including next-generation sequencing and some accompanying methods. In conclusion, the important role of the joint use of genomics and proteomics approaches in understanding the molecular genetic bases of adaptation is emphasized.

  6. A Novel Methodology for Metal Ion Separation Based on Molecularly Imprinting

    SciTech Connect

    Zuo, Xiaobin; Mosha, Donnati; Hassan, Mansour M.; Givens, Richard S.; Busch, Daryle H.

    2004-03-31

    The siderophore-based extraction of iron from the soil by bacteria is proposed as a model for a new separation methodology labeled the soil poutice, a molecular device that would selectively retrieve the complex of a targeted metal ion. In this report we described the synthesis and characterization of molecularly imprinted polymers and their application in the specific recognition of macrocyclic metal complexes. The imprinting is based on non-covalent interactions such as hydrogen bonding, electrostatic attractions and minor metal-ligand coordination. Good rebinding capacity for the imprinting metal complex was observed in acetonitrile as well as in water. The polymers are resistant to strong acids and oxidizing agents and showed an increase of rebinding capacity during cycles of reuse. The imprinting procedure, combined with the previously known selective chelation of macrocyclic ligands, supports the feasibility of a new methodology that can be used to extract waste metal ions effectively and selectively from soils and ground water.

  7. A chemically powered unidirectional rotary molecular motor based on a palladium redox cycle

    NASA Astrophysics Data System (ADS)

    Collins, Beatrice S. L.; Kistemaker, Jos C. M.; Otten, Edwin; Feringa, Ben L.

    2016-09-01

    The conversion of chemical energy to drive directional motion at the molecular level allows biological systems, ranging from subcellular components to whole organisms, to perform a myriad of dynamic functions and respond to changes in the environment. Directional movement has been demonstrated in artificial molecular systems, but the fundamental motif of unidirectional rotary motion along a single-bond rotary axle induced by metal-catalysed transformation of chemical fuels has not been realized, and the challenge is to couple the metal-centred redox processes to stepwise changes in conformation to arrive at a full unidirectional rotary cycle. Here, we present the design of an organopalladium-based motor and the experimental demonstration of a 360° unidirectional rotary cycle using simple chemical fuels. Exploiting fundamental reactivity principles in organometallic chemistry enables control of directional rotation and offers the potential of harnessing the wealth of opportunities offered by transition-metal-based catalytic conversions to drive motion and dynamic functions.

  8. Polymerase chain reaction-based molecular diagnosis of cutaneous infections in dermatopathology.

    PubMed

    Swick, Brian L

    2012-12-01

    Conventional methods, including microscopy, culture, and serologic studies, are a mainstay in the diagnosis of cutaneous infection. However, owing to limitations associated with these techniques, such as low sensitivity for standard microscopy and in the case of culture delay in diagnosis, polymerase chain-reaction based molecular techniques have taken on an expanding role in the diagnosis of infectious processes in dermatopathology. In particular, these assays are a useful adjunct in the diagnosis of cutaneous tuberculosis, atypical mycobacterial infection, leprosy, Lyme disease, syphilis, rickettsioses, leishmaniasis, and some fungal and viral infections. Already in the case of tuberculosis and atypical mycobacterial infection, standardized polymerase chain-reaction assays are commonly used for diagnostic purposes. With time, additional molecular-based techniques will decrease in cost and gain increased standardization, thus delivering rapid diagnostic confirmation for many difficult-to-diagnose cutaneous infections from standard formalin-fixed paraffin-embedded tissue specimens.

  9. Efficient electronic coupling and improved stability with dithiocarbamate-based molecular junctions

    NASA Astrophysics Data System (ADS)

    von Wrochem, Florian; Gao, Deqing; Scholz, Frank; Nothofer, Heinz-Georg; Nelles, Gabriele; Wessels, Jurina M.

    2010-08-01

    Molecular electronic devices require stable and highly conductive contacts between the metal electrodes and molecules. Thiols and amines are widely used to attach molecules to metals, but they form poor electrical contacts and lack the robustness required for device applications. Here, we demonstrate that dithiocarbamates provide superior electrical contact and thermal stability when compared to thiols on metals. Ultraviolet photoelectron spectroscopy and density functional theory show the presence of electronic states at 0.6 eV below the Fermi level of Au, which effectively reduce the charge injection barrier across the metal-molecule interface. Charge transport measurements across oligophenylene monolayers reveal that the conductance of terphenyl-dithiocarbamate junctions is two orders of magnitude higher than that of terphenyl-thiolate junctions. The stability and low contact resistance of dithiocarbamate-based molecular junctions represent a significant step towards the development of robust, organic-based electronic circuits.

  10. Efficient electronic coupling and improved stability with dithiocarbamate-based molecular junctions.

    PubMed

    von Wrochem, Florian; Gao, Deqing; Scholz, Frank; Nothofer, Heinz-Georg; Nelles, Gabriele; Wessels, Jurina M

    2010-08-01

    Molecular electronic devices require stable and highly conductive contacts between the metal electrodes and molecules. Thiols and amines are widely used to attach molecules to metals, but they form poor electrical contacts and lack the robustness required for device applications. Here, we demonstrate that dithiocarbamates provide superior electrical contact and thermal stability when compared to thiols on metals. Ultraviolet photoelectron spectroscopy and density functional theory show the presence of electronic states at 0.6 eV below the Fermi level of Au, which effectively reduce the charge injection barrier across the metal-molecule interface. Charge transport measurements across oligophenylene monolayers reveal that the conductance of terphenyl-dithiocarbamate junctions is two orders of magnitude higher than that of terphenyl-thiolate junctions. The stability and low contact resistance of dithiocarbamate-based molecular junctions represent a significant step towards the development of robust, organic-based electronic circuits. PMID:20562871

  11. A density-based adaptive quantum mechanical/molecular mechanical method.

    PubMed

    Waller, Mark P; Kumbhar, Sadhana; Yang, Jack

    2014-10-20

    We present a density-based adaptive quantum mechanical/molecular mechanical (DBA-QM/MM) method, whereby molecules can switch layers from the QM to the MM region and vice versa. The adaptive partitioning of the molecular system ensures that the layer assignment can change during the optimization procedure, that is, on the fly. The switch from a QM molecule to a MM molecule is determined if there is an absence of noncovalent interactions to any atom of the QM core region. The presence/absence of noncovalent interactions is determined by analysis of the reduced density gradient. Therefore, the location of the QM/MM boundary is based on physical arguments, and this neatly removes some empiricism inherent in previous adaptive QM/MM partitioning schemes. The DBA-QM/MM method is validated by using a water-in-water setup and an explicitly solvated L-alanyl-L-alanine dipeptide. PMID:24954803

  12. A density-based adaptive quantum mechanical/molecular mechanical method.

    PubMed

    Waller, Mark P; Kumbhar, Sadhana; Yang, Jack

    2014-10-20

    We present a density-based adaptive quantum mechanical/molecular mechanical (DBA-QM/MM) method, whereby molecules can switch layers from the QM to the MM region and vice versa. The adaptive partitioning of the molecular system ensures that the layer assignment can change during the optimization procedure, that is, on the fly. The switch from a QM molecule to a MM molecule is determined if there is an absence of noncovalent interactions to any atom of the QM core region. The presence/absence of noncovalent interactions is determined by analysis of the reduced density gradient. Therefore, the location of the QM/MM boundary is based on physical arguments, and this neatly removes some empiricism inherent in previous adaptive QM/MM partitioning schemes. The DBA-QM/MM method is validated by using a water-in-water setup and an explicitly solvated L-alanyl-L-alanine dipeptide.

  13. Development of a molecularly imprinted polymer based surface plasmon resonance sensor for theophylline monitoring

    NASA Astrophysics Data System (ADS)

    Zheng, Rui; Cameron, Brent D.

    2011-03-01

    Molecularly imprinted polymer (MIP) thin films and surface plasmon resonance (SPR) sensing technologies were combined to develop a novel sensing platform for monitoring real-time theophylline concentration, which is a compound of interest in environmental monitoring and a molecular probe for phenotyping certain cytochrome P450 enzymes. The MIPs hydrogel is easy to synthesize and provides shape-selective recognition with high affinity to specific target molecules. Different polymerization formulas were tested and optimized. The influence of the monomer sensitive factors were addressed by SPR. SPR is an evanescent wave optics based sensing technique that is suitable for real-time and label free sensing purposes. Gold nanorods (Au NRs) were uniformly immobilized onto a SPR sensing surface for the construction of a fiber optics based prism-free localized SPR (LSPR) measurement. This technique can be also applied to assess the activities of other small organic molecules by adjusting the polymerization formula, thus, this approach also has many other potential applications.

  14. Low molecular weight Neutral Boron Dipyrromethene (Bodipy) dyads for fluorescence-based neural imaging

    NASA Astrophysics Data System (ADS)

    Bai, Dan; Benniston, Andrew C.; Clift, Sophie; Baisch, Ulrich; Steyn, Jannetta; Everitt, Nicola; Andras, Peter

    2014-05-01

    The neutral low molecular weight julolidine-based borondipyrromethene (Bodipy) dyads JULBD and MJULBD were used for fast voltage-sensitive dye imaging of neurons in the crab stomatogastric ganglion. The fluorescence modulation of the dyads mirrors alterations in the membrane potential of the imaged neurons. The toxicity of the dyes towards the neurons is related to their structure in that methyl groups at the 3,5 positions results in reduced toxic effects.

  15. Dithienogermole-based solution-processed molecular solar cells with efficiency over 9.

    PubMed

    Gupta, Vinay; Lai, Lai Fan; Datt, Ram; Chand, Suresh; Heeger, Alan J; Bazan, Guillermo C; Singh, Surya Prakash

    2016-06-30

    A molecular donor of intermediate dimensions based on dithienogermole (DTG) as the central electron rich unit, coded as DTG(FBT2Th2)2, was designed and synthesized for use in bulk heterojunction, solution-processed organic solar cells. Under optimized conditions, a maximum power conversion efficiency (PCE) of 9.1% can be achieved with [6,6]-phenyl C71-butyric acid methyl ester (PC71BM) as the acceptor semiconductor component. PMID:27321642

  16. Synthetic molecular systems based on porphyrins as models for the study of energy transfer in photosynthesis

    NASA Astrophysics Data System (ADS)

    Konovalova, Nadezhda V.; Evstigneeva, Rima P.; Luzgina, Valentina N.

    2001-11-01

    The published data on the synthesis and photochemical properties of porphyrin-based molecular ensembles which represent models of natural photosynthetic light-harvesting complexes are generalised and systematised. The dependence of the transfer of excitation energy on the distance between donor and acceptor components, their mutual arrangement, electronic and environmental factors are discussed. Two mechanisms of energy transfer reactions, viz., 'through space' and 'through bond', are considered. The bibliography includes 96 references.

  17. Playing Tic-Tac-Toe with a Sugar-Based Molecular Computer.

    PubMed

    Elstner, M; Schiller, A

    2015-08-24

    Today, molecules can perform Boolean operations and circuits at a level of higher complexity. However, concatenation of logic gates and inhomogeneous inputs and outputs are still challenging tasks. Novel approaches for logic gate integration are possible when chemical programming and software programming are combined. Here it is shown that a molecular finite automaton based on the concatenated implication function (IMP) of a fluorescent two-component sugar probe via a wiring algorithm is able to play tic-tac-toe.

  18. Phthalocyanine dimerization-based molecular beacons using near-IR fluorescence.

    PubMed

    Nesterova, Irina V; Erdem, S Sibel; Pakhomov, Serhii; Hammer, Robert P; Soper, Steven A

    2009-02-25

    Herein we demonstrate the use of a novel dimerization-based molecular beacon (MB) probe consisting of two metallo-phthalocyanine (Pc) fluorophores that use near-IR fluorescence, appropriate for highly specific and sensitive in vivo and/or in vitro DNA/RNA detection. Pc's possess a propensity to form nonfluorescent H-dimers that is utilized as the molecular "off" switch in the closed MB conformation. The "on" switch, which is generated when the solution target binds to the loop of the MB forming the open form, also provides two fluorophores for transduction resulting in a doubling of the extinction coefficient and improving the resulting fluorescence yield compared to a classical single-fluorophore/quencher MB system. In addition, the Pc-based MBs possess high thermal, photo, and chemical stabilities that are essential for many highly sensitive applications, such as molecular imaging. The dimer-based MBs were obtained using a simple single-step synthesis procedure and demonstrated excellent quenching efficiencies (98%) as well as a high signal-to-background ratio (approximately 60) exceeding the performance characteristics of many conventionally available MB probes.

  19. An efficient fluorescent sensing platform for biomolecules based on fenton reaction triggered molecular beacon cleavage strategy.

    PubMed

    Hu, Rong; Liu, Ya-Ru; Zhang, Xiao-Bing; Tan, Weihong; Shen, Guo-Li; Yu, Ru-Qin

    2013-03-15

    A universal sensing platform for fluorescence turn-on detection of biomolecules is developed based on Fenton reaction triggered molecular beacon cleavage. Due to its high quenching efficiency, molecular beacons (MBs)-based sensing systems usually show low background fluorescence and large signal-to-background ratio. Glucose is chosen as a model biomolecule for constructing an MB-based fluorescence sensing system. In the presence of glucose, the glucose oxidase will bind with it and catalyze the oxidation to generate H(2)O(2), which is further decomposed to produce (·)OH through the Fe(2+)-catalyzed Fenton reaction. Then, in-situ-generated OH can trigger the cleavage of the MB, and its fluorescence intensity will be dramatically increased because of the complete separation of the fluorophore from the quencher. By employing molecular beacon as both recognition and reporter probes to low background signal, the proposed biosensors showed high sensitivity to targets. It also exhibited high selectivity owing to the high specificity of the enzymatic oxidation, which make it valuable for the detection of target biomolecule in complex biological samples.

  20. Feasibility study of molecular memory device based on DNA using methylation to store information

    NASA Astrophysics Data System (ADS)

    Jiang, Liming; Qiu, Wanzhi; Al-Dirini, Feras; Hossain, Faruque M.; Evans, Robin; Skafidas, Efstratios

    2016-07-01

    DNA, because of its robustness and dense information storage capability, has been proposed as a potential candidate for next-generation storage media. However, encoding information into the DNA sequence requires molecular synthesis technology, which to date is costly and prone to synthesis errors. Reading the DNA strand information is also complex. Ideally, DNA storage will provide methods for modifying stored information. Here, we conduct a feasibility study investigating the use of the DNA 5-methylcytosine (5mC) methylation state as a molecular memory to store information. We propose a new 1-bit memory device and study, based on the density functional theory and non-equilibrium Green's function method, the feasibility of electrically reading the information. Our results show that changes to methylation states lead to changes in the peak of negative differential resistance which can be used to interrogate memory state. Our work demonstrates a new memory concept based on methylation state which can be beneficial in the design of next generation DNA based molecular electronic memory devices.

  1. Hybrid schemes based on quantum mechanics/molecular mechanics simulations goals to success, problems, and perspectives.

    PubMed

    Ferrer, Silvia; Ruiz-Pernía, Javier; Martí, Sergio; Moliner, Vicent; Tuñón, Iñaki; Bertrán, Juan; Andrés, Juan

    2011-01-01

    The development of characterization techniques, advanced synthesis methods, as well as molecular modeling has transformed the study of systems in a well-established research field. The current research challenges in biocatalysis and biotransformation evolve around enzyme discovery, design, and optimization. How can we find or create enzymes that catalyze important synthetic reactions, even reactions that may not exist in nature? What is the source of enzyme catalytic power? To answer these and other related questions, the standard strategies have evolved from trial-and-error methodologies based on chemical knowledge, accumulated experience, and common sense into a clearly multidisciplinary science that allows one to reach the molecular design of tailor-made enzyme catalysts. This is even more so when one refers to enzyme catalysts, for which the detailed structure and composition are known and can be manipulated to introduce well-defined residues which can be implicated in the chemical rearrangements taking place in the active site. The methods and techniques of theoretical and computational chemistry are becoming more and more important in both understanding the fundamental biological roles of enzymes and facilitating their utilization in biotechnology. Improvement of the catalytic function of enzymes is important from scientific and industrial viewpoints, and to put this fact in the actual perspective as well as the potentialities, we recommend the very recent report of Sanderson [Sanderson, K. (2011). Chemistry: enzyme expertise. Nature 471, 397.]. Great fundamental advances have been made toward the ab initio design of enzyme catalysts based on molecular modeling. This has been based on the molecular mechanistic knowledge of the reactions to be catalyzed, together with the development of advanced synthesis and characterization techniques. The corresponding molecular mechanism can be studied by means of powerful quantum chemical calculations. The catalytic

  2. Synchrotron based mass spectrometry to investigate the molecular properties of mineral-organic associations

    SciTech Connect

    Liu, Suet Yi; Kleber, Markus; Takahashi, Lynelle K.; Nico, Peter; Keiluweit, Marco; Ahmed, Musahid

    2013-04-01

    Soil organic matter (OM) is important because its decay drives life processes in the biosphere. Analysis of organic compounds in geological systems is difficult because of their intimate association with mineral surfaces. To date there is no procedure capable of quantitatively separating organic from mineral phases without creating artifacts or mass loss. Therefore, analytical techniques that can (a) generate information about both organic and mineral phases simultaneously and (b) allow the examination of predetermined high-interest regions of the sample as opposed to conventional bulk analytical techniques are valuable. Laser Desorption Synchrotron Postionization (synchrotron-LDPI) mass spectrometry is introduced as a novel analytical tool to characterize the molecular properties of organic compounds in mineral-organic samples from terrestrial systems, and it is demonstrated that when combined with Secondary Ion Mass Spectrometry (SIMS), can provide complementary information on mineral composition. Mass spectrometry along a decomposition gradient in density fractions, verifies the consistency of our results with bulk analytical techniques. We further demonstrate that by changing laser and photoionization energies, variations in molecular stability of organic compounds associated with mineral surfaces can be determined. The combination of synchrotron-LDPI and SIMS shows that the energetic conditions involved in desorption and ionization of organic matter may be a greater determinant of mass spectral signatures than the inherent molecular structure of the organic compounds investigated. The latter has implications for molecular models of natural organic matter that are based on mass spectrometric information.

  3. Fiber optic profenofos sensor based on surface plasmon resonance technique and molecular imprinting.

    PubMed

    Shrivastav, Anand M; Usha, Sruthi P; Gupta, Banshi D

    2016-05-15

    A successful approach for the fabrication and characterization of an optical fiber sensor for the detection of profenofos based on surface plasmon resonance (SPR) and molecular imprinting is introduced. Molecular imprinting technology is used for the creation of three dimensional binding sites having complementary shape and size of the specific template molecule over a polymer for the recognition of the same. Binding of template molecule with molecularly imprinted polymer (MIP) layer results in the change in the dielectric nature of the sensing surface (polymer) and is identified by SPR technique. Spectral interrogation method is used for the characterization of the sensing probe. The operating profenofos concentration range of the sensor is from 10(-4) to 10(-1)µg/L. A red shift of 18.7 nm in resonance wavelength is recorded for this profenofos concentration range. The maximum sensitivity of the sensor is 12.7 nm/log (µg/L) at 10(-4)µg/L profenofos concentration. Limit of detection (LOD) of the sensor is found to be 2.5×10(-6)µg/L. Selectivity measurements predict the probe highly selective for the profenofos molecule. Besides high sensitivity due to SPR technique and selectivity due to molecular imprinting, proposed sensor has numerous other advantages like immunity to electromagnetic interference, fast response, low cost and capability of online monitoring and remote sensing of analyte due to the fabrication of the probe on optical fiber.

  4. Fiber optic profenofos sensor based on surface plasmon resonance technique and molecular imprinting.

    PubMed

    Shrivastav, Anand M; Usha, Sruthi P; Gupta, Banshi D

    2016-05-15

    A successful approach for the fabrication and characterization of an optical fiber sensor for the detection of profenofos based on surface plasmon resonance (SPR) and molecular imprinting is introduced. Molecular imprinting technology is used for the creation of three dimensional binding sites having complementary shape and size of the specific template molecule over a polymer for the recognition of the same. Binding of template molecule with molecularly imprinted polymer (MIP) layer results in the change in the dielectric nature of the sensing surface (polymer) and is identified by SPR technique. Spectral interrogation method is used for the characterization of the sensing probe. The operating profenofos concentration range of the sensor is from 10(-4) to 10(-1)µg/L. A red shift of 18.7 nm in resonance wavelength is recorded for this profenofos concentration range. The maximum sensitivity of the sensor is 12.7 nm/log (µg/L) at 10(-4)µg/L profenofos concentration. Limit of detection (LOD) of the sensor is found to be 2.5×10(-6)µg/L. Selectivity measurements predict the probe highly selective for the profenofos molecule. Besides high sensitivity due to SPR technique and selectivity due to molecular imprinting, proposed sensor has numerous other advantages like immunity to electromagnetic interference, fast response, low cost and capability of online monitoring and remote sensing of analyte due to the fabrication of the probe on optical fiber. PMID:26706813

  5. Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland

    PubMed Central

    Zhao, Li; Wang, Feng; Wang, Hui; Li, Yumei; Alexander, Sharon; Wang, Keqing; Willoughby, Colin E.; Zaneveld, Jacques E.; Jiang, Lichun; Soens, Zachry T.; Earle, Philip; Simpson, David

    2015-01-01

    Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive photoreceptor degeneration. An accurate molecular diagnosis is essential for disease characterization and clinical prognoses. A retinal capture panel that enriches 186 known retinal disease genes, including 55 known RP genes, was developed. Targeted next-generation sequencing was performed for a cohort of 82 unrelated RP cases from Northern Ireland, including 46 simplex cases and 36 familial cases. Disease-causing mutations were identified in 49 probands, including 28 simplex cases and 21 familial cases, achieving a solving rate of 60 %. In total, 65 pathogenic mutations were found, and 29 of these were novel. Interestingly, the molecular information of 12 probands was neither consistent with their initial inheritance pattern nor clinical diagnosis. Further clinical reassessment resulted in a refinement of the clinical diagnosis in 11 patients. This is the first study to apply next-generation sequencing-based, comprehensive molecular diagnoses to a large number of RP probands from Northern Ireland. Our study shows that molecular information can aid clinical diagnosis, potentially changing treatment options, current family counseling and management. PMID:25472526

  6. NGS-based Molecular diagnosis of 105 eyeGENE(®) probands with Retinitis Pigmentosa.

    PubMed

    Ge, Zhongqi; Bowles, Kristen; Goetz, Kerry; Scholl, Hendrik P N; Wang, Feng; Wang, Xinjing; Xu, Shan; Wang, Keqing; Wang, Hui; Chen, Rui

    2015-12-15

    The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE(®)) was established in an effort to facilitate basic and clinical research of human inherited eye disease. In order to provide high quality genetic testing to eyeGENE(®)'s enrolled patients which potentially aids clinical diagnosis and disease treatment, we carried out a pilot study and performed Next-generation sequencing (NGS) based molecular diagnosis for 105 Retinitis Pigmentosa (RP) patients randomly selected from the network. A custom capture panel was designed, which incorporated 195 known retinal disease genes, including 61 known RP genes. As a result, disease-causing mutations were identified in 52 out of 105 probands (solving rate of 49.5%). A total of 82 mutations were identified, and 48 of them were novel. Interestingly, for three probands the molecular diagnosis was inconsistent with the initial clinical diagnosis, while for five probands the molecular information suggested a different inheritance model other than that assigned by the physician. In conclusion, our study demonstrated that NGS target sequencing is efficient and sufficiently precise for molecular diagnosis of a highly heterogeneous patient cohort from eyeGENE(®).

  7. Genetic and molecular bases of photoperiod responses of flowering in soybean.

    PubMed

    Watanabe, Satoshi; Harada, Kyuya; Abe, Jun

    2012-01-01

    Flowering is one of the most important processes involved in crop adaptation and productivity. A number of major genes and quantitative trait loci (QTLs) for flowering have been reported in soybean (Glycine max). These genes and QTLs interact with one another and with the environment to greatly influence not only flowering and maturity but also plant morphology, final yield, and stress tolerance. The information available on the soybean genome sequence and on the molecular bases of flowering in Arabidopsis will undoubtedly facilitate the molecular dissection of flowering in soybean. Here, we review the present status of our understanding of the genetic and molecular mechanisms of flowering in soybean. We also discuss our identification of orthologs of Arabidopsis flowering genes from among the 46,367 genes annotated in the publicly available soybean genome database Phytozome Glyma 1.0. We emphasize the usefulness of a combined approach including QTL analysis, fine mapping, and use of candidate gene information from model plant species in genetic and molecular studies of soybean flowering. PMID:23136492

  8. Wide-field fluorescence molecular tomography with compressive sensing based preconditioning

    PubMed Central

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-01-01

    Wide-field optical tomography based on structured light illumination and detection strategies enables efficient tomographic imaging of large tissues at very fast acquisition speeds. However, the optical inverse problem based on such instrumental approach is still ill-conditioned. Herein, we investigate the benefit of employing compressive sensing-based preconditioning to wide-field structured illumination and detection approaches. We assess the performances of Fluorescence Molecular Tomography (FMT) when using such preconditioning methods both in silico and with experimental data. Additionally, we demonstrate that such methodology could be used to select the subset of patterns that provides optimal reconstruction performances. Lastly, we compare preconditioning data collected using a normal base that offers good experimental SNR against that directly acquired with optimal designed base. An experimental phantom study is provided to validate the proposed technique. PMID:26713202

  9. Wide-field fluorescence molecular tomography with compressive sensing based preconditioning.

    PubMed

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-12-01

    Wide-field optical tomography based on structured light illumination and detection strategies enables efficient tomographic imaging of large tissues at very fast acquisition speeds. However, the optical inverse problem based on such instrumental approach is still ill-conditioned. Herein, we investigate the benefit of employing compressive sensing-based preconditioning to wide-field structured illumination and detection approaches. We assess the performances of Fluorescence Molecular Tomography (FMT) when using such preconditioning methods both in silico and with experimental data. Additionally, we demonstrate that such methodology could be used to select the subset of patterns that provides optimal reconstruction performances. Lastly, we compare preconditioning data collected using a normal base that offers good experimental SNR against that directly acquired with optimal designed base. An experimental phantom study is provided to validate the proposed technique.

  10. RNA-templated single-base mutation detection based on T4 DNA ligase and reverse molecular beacon.

    PubMed

    Tang, Hongxing; Yang, Xiaohai; Wang, Kemin; Tan, Weihong; Li, Huimin; He, Lifang; Liu, Bin

    2008-06-15

    A novel RNA-templated single-base mutation detection method based on T4 DNA ligase and reverse molecular beacon (rMB) has been developed and successfully applied to identification of single-base mutation in codon 273 of the p53 gene. The discrimination was carried out using allele-specific primers, which flanked the variable position in the target RNA and was ligated using T4 DNA ligase only when the primers perfectly matched the RNA template. The allele-specific primers also carried complementary stem structures with end-labels (fluorophore TAMRA, quencher DABCYL), which formed a molecular beacon after RNase H digestion. One-base mismatch can be discriminated by analyzing the change of fluorescence intensity before and after RNase H digestion. This method has several advantages for practical applications, such as direct discrimination of single-base mismatch of the RNA extracted from cell; no requirement of PCR amplification; performance of homogeneous detection; and easily design of detection probes.

  11. Rectifying Properties of a Nitrogen/Boron-Doped Capped-Carbon-Nanotube-Based Molecular Junction

    NASA Astrophysics Data System (ADS)

    Zhao, Peng; Liu, De-Sheng; Zhang, Ying; Wang, Pei-Ji; Zhang, Zhong

    2011-04-01

    Based on the non-equilibrium Green's function method and first-principles density functional theory calculations, we investigate the electronic transport properties of a nitrogen/boron-doped capped-single-walled carbon-nanotube-based molecular junction. Obvious rectifying behavior is observed and it is strongly dependent on the doping site. The best rectifying performance can be carried out when the nitrogen/boron atom dopes at a carbon site in the second layer. Moreover, the rectifying performance can be further improved by adjusting the distance between the C60 nanotube caps.

  12. Construction of the Fock Matrix on a Grid-Based Molecular Orbital Basis Using GPGPUs.

    PubMed

    Losilla, Sergio A; Watson, Mark A; Aspuru-Guzik, Alán; Sundholm, Dage

    2015-05-12

    We present a GPGPU implementation of the construction of the Fock matrix in the molecular orbital basis using the fully numerical, grid-based bubbles representation. For a test set of molecules containing up to 90 electrons, the total Hartree-Fock energies obtained from reference GTO-based calculations are reproduced within 10(-4) Eh to 10(-8) Eh for most of the molecules studied. Despite the very large number of arithmetic operations involved, the high performance obtained made the calculations possible on a single Nvidia Tesla K40 GPGPU card.

  13. Initiating heavy-atom-based phasing by multi-dimensional molecular replacement

    PubMed Central

    Pedersen, Bjørn Panyella; Gourdon, Pontus; Liu, Xiangyu; Karlsen, Jesper Lykkegaard; Nissen, Poul

    2016-01-01

    To obtain an electron-density map from a macromolecular crystal the phase problem needs to be solved, which often involves the use of heavy-atom derivative crystals and concomitant heavy-atom substructure determination. This is typically performed by dual-space methods, direct methods or Patterson-based approaches, which however may fail when only poorly diffracting derivative crystals are available. This is often the case for, for example, membrane proteins. Here, an approach for heavy-atom site identification based on a molecular-replacement parameter matrix (MRPM) is presented. It involves an n-dimensional search to test a wide spectrum of molecular-replacement parameters, such as different data sets and search models with different conformations. Results are scored by the ability to identify heavy-atom positions from anomalous difference Fourier maps. The strategy was successfully applied in the determination of a membrane-protein structure, the copper-transporting P-type ATPase CopA, when other methods had failed to determine the heavy-atom substructure. MRPM is well suited to proteins undergoing large conformational changes where multiple search models should be considered, and it enables the identification of weak but correct molecular-replacement solutions with maximum contrast to prime experimental phasing efforts. PMID:26960131

  14. Fluorescent DNAzyme biosensors for metal ions based on catalytic molecular beacons.

    PubMed

    Liu, Juewen; Lu, Yi

    2006-01-01

    In this chapter, methods for designing metal ion sensors using fluorophore- and quencher-labeled DNAzymes are discussed. In contrast to the classical molecular beacon method based on binding, the methods described here utilize catalytic cleavage to release the fluorophore for detection and quantification, making it possible to take advantage of catalytic turnovers for signal amplification. Unlike classical molecular beacons that detect only nucleic acids, catalytic molecular beacons can be applied to different DNAzymes to detect a broad range of analytes. The methods described are based on the finding that almost all known trans-cleaving DNAzymes share a similar structure comprised of a catalytic DNAzyme core flanked by two substrate recognition arms. Using a typical DNAzyme called the "8-17" DNAzyme as an example, the design of highly sensitive and selective Pb2+ sensors is described in detail. The initial design employs a single fluorophore-quencher pair in close proximity, with the fluorophore on the 5'-end of the substrate and the quencher on the 3'-end of the enzyme. Although this sensor is highly sensitive and selective at 4 degrees C, high background fluorescence is observed at higher temperatures. Therefore a new design with an additional quencher attached to the 3'-end of the substrate is employed to suppress background fluorescence. The dual quencher method allows the sensor to perform at ambient temperatures with a high signal-to-noise ratio.

  15. Initiating heavy-atom-based phasing by multi-dimensional molecular replacement.

    PubMed

    Pedersen, Bjørn Panyella; Gourdon, Pontus; Liu, Xiangyu; Karlsen, Jesper Lykkegaard; Nissen, Poul

    2016-03-01

    To obtain an electron-density map from a macromolecular crystal the phase problem needs to be solved, which often involves the use of heavy-atom derivative crystals and concomitant heavy-atom substructure determination. This is typically performed by dual-space methods, direct methods or Patterson-based approaches, which however may fail when only poorly diffracting derivative crystals are available. This is often the case for, for example, membrane proteins. Here, an approach for heavy-atom site identification based on a molecular-replacement parameter matrix (MRPM) is presented. It involves an n-dimensional search to test a wide spectrum of molecular-replacement parameters, such as different data sets and search models with different conformations. Results are scored by the ability to identify heavy-atom positions from anomalous difference Fourier maps. The strategy was successfully applied in the determination of a membrane-protein structure, the copper-transporting P-type ATPase CopA, when other methods had failed to determine the heavy-atom substructure. MRPM is well suited to proteins undergoing large conformational changes where multiple search models should be considered, and it enables the identification of weak but correct molecular-replacement solutions with maximum contrast to prime experimental phasing efforts.

  16. Spin-dependent Otto quantum heat engine based on a molecular substance

    NASA Astrophysics Data System (ADS)

    Hübner, W.; Lefkidis, G.; Dong, C. D.; Chaudhuri, D.; Chotorlishvili, L.; Berakdar, J.

    2014-07-01

    We explore the potential of single molecules for thermodynamic cycles. To this end we propose two molecular heat engines based on the Ni2 dimer in the presence of a static magnetic field: (a) a quantum Otto engine and (b) a modified quantum Otto engine for which optical excitations induced by a laser pulse substitute for one of the heat-exchange points. For reliable predictions and to inspect the role of spin and electronic correlations we perform fully correlated ab initio calculations of the molecular electronic structure including spin-orbital effects. We analyze the efficiency of the engines in dependence of the electronic level scheme and the entanglement and find a significant possible enhancement connected to the quantum nature and the heat capacity of the dimer, as well as to the zero-field triplet states splitting.

  17. First-principles studies on switching properties of azobenzene based molecular device

    NASA Astrophysics Data System (ADS)

    Dhivya, G.; Nagarajan, V.; Chandiramouli, R.

    2016-09-01

    The switching behavior of cis and trans-azobenzene molecular device is studied using DFT method in combination with non-equilibrium Green's function. The peak maximum is found to be more in the density of states spectrum for trans-azobenzene device rather than cis-azobenzene device due to direct link of two phenyl group by Ndbnd N bonds. The current voltage characteristics clearly show the closed configuration of cis-azobenzene and open configuration of trans-azobenzene, which is attributed through the HOMO and LUMO level of cis and trans isomers. The observations of the present work give an insight on switching behavior of azobenzene based molecular device in the atomistic level.

  18. Titanium compounds as catalysts of higher alpha-olefin-based super-high-molecular polymers synthesis

    NASA Astrophysics Data System (ADS)

    Konovalov, K. B.; Kazaryan, M. A.; Manzhay, V. N.; Vetrova, O. V.

    2016-01-01

    The synthesis of polymers of 10 million or more molecular weight is a difficult task even in a chemical lab. Higher α-olefin-based polymer agents of such kind have found a narrow but quite important niche, the reduction of drag in the turbulent flow of hydrocarbon fluids such as oil and oil-products. In its turn, searching for a catalytic system capable to produce molecules of such a high length and to synthesize polymers of a low molecular-mass distribution is part of a global task of obtaining a high-quality product. In this paper we had observed a number of industrial catalysts with respect to their suitability for higher poly-α- olefins synthesis. A number samples representing copolymers of 1-hexene with 1-decene obtained on a previous generation catalyst, a microsphere titanium chloride catalytic agent had been compared to samples synthesized using a titanium-magnesium catalyst both in solution and in a polymer medium.

  19. Restoring electronic coherence/decoherence for a trajectory-based nonadiabatic molecular dynamics

    PubMed Central

    Zhu, Chaoyuan

    2016-01-01

    By utilizing the time-independent semiclassical phase integral, we obtained modified coupled time-dependent Schrödinger equations that restore coherences and induce decoherences within original simple trajectory-based nonadiabatic molecular dynamic algorithms. Nonadiabatic transition probabilities simulated from both Tully’s fewest switches and semiclassical Ehrenfest algorithms follow exact quantum electronic oscillations and amplitudes for three out of the four well-known model systems. Within the present theory, nonadiabatic transitions estimated from statistical ensemble of trajectories accurately follow those of the modified electronic wave functions. The present theory can be immediately applied to the molecular dynamic simulations of photochemical and photophysical processes involving electronic excited states. PMID:27063337

  20. Self-consistent field theory based molecular dynamics with linear system-size scaling

    SciTech Connect

    Richters, Dorothee; Kühne, Thomas D.

    2014-04-07

    We present an improved field-theoretic approach to the grand-canonical potential suitable for linear scaling molecular dynamics simulations using forces from self-consistent electronic structure calculations. It is based on an exact decomposition of the grand canonical potential for independent fermions and does neither rely on the ability to localize the orbitals nor that the Hamilton operator is well-conditioned. Hence, this scheme enables highly accurate all-electron linear scaling calculations even for metallic systems. The inherent energy drift of Born-Oppenheimer molecular dynamics simulations, arising from an incomplete convergence of the self-consistent field cycle, is circumvented by means of a properly modified Langevin equation. The predictive power of the present approach is illustrated using the example of liquid methane under extreme conditions.

  1. Determination of Quantum Chemistry Based Force Fields for Molecular Dynamics Simulations of Aromatic Polymers

    NASA Technical Reports Server (NTRS)

    Jaffe, Richard; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    Ab initio quantum chemistry calculations for model molecules can be used to parameterize force fields for molecular dynamics simulations of polymers. Emphasis in our research group is on using quantum chemistry-based force fields for molecular dynamics simulations of organic polymers in the melt and glassy states, but the methodology is applicable to simulations of small molecules, multicomponent systems and solutions. Special attention is paid to deriving reliable descriptions of the non-bonded and electrostatic interactions. Several procedures have been developed for deriving and calibrating these parameters. Our force fields for aromatic polyimide simulations will be described. In this application, the intermolecular interactions are the critical factor in determining many properties of the polymer (including its color).

  2. Self-consistent field theory based molecular dynamics with linear system-size scaling.

    PubMed

    Richters, Dorothee; Kühne, Thomas D

    2014-04-01

    We present an improved field-theoretic approach to the grand-canonical potential suitable for linear scaling molecular dynamics simulations using forces from self-consistent electronic structure calculations. It is based on an exact decomposition of the grand canonical potential for independent fermions and does neither rely on the ability to localize the orbitals nor that the Hamilton operator is well-conditioned. Hence, this scheme enables highly accurate all-electron linear scaling calculations even for metallic systems. The inherent energy drift of Born-Oppenheimer molecular dynamics simulations, arising from an incomplete convergence of the self-consistent field cycle, is circumvented by means of a properly modified Langevin equation. The predictive power of the present approach is illustrated using the example of liquid methane under extreme conditions.

  3. Spatial distribution of phases during gradual magnetostructural transitions in copper(II)-nitroxide based molecular magnets.

    PubMed

    Fedin, Matvey V; Veber, Sergey L; Bagryanskaya, Elena G; Romanenko, Galina V; Ovcharenko, Victor I

    2015-11-21

    Copper(ii)-nitroxide based molecular magnets Cu(hfac)2L(R) exhibit thermally-induced transitions between high- and low-temperature (HT/LT) magnetostructural states. In this work we report the first study on the spatial distribution of HT/LT phases during gradual transitions in these compounds. We explore the possibility of domain formation at intermediate temperatures, which has never been addressed before. For this purpose, we reexamine the available electron paramagnetic resonance (EPR) and X-ray diffraction data, and perform numerical calculations of EPR spectra for different models of exchange-coupled networks. A thorough analysis shows that during gradual transitions, molecular magnets Cu(hfac)2L(R) represent solid solutions of disordered HT and LT phases, and the formation of single-phase domains larger than a few nanometers in size is unlikely.

  4. G-quadruplex DNAzyme based molecular catalytic beacon for label-free colorimetric logic gates.

    PubMed

    Zhu, Jinbo; Li, Tao; Zhang, Libing; Dong, Shaojun; Wang, Erkang

    2011-10-01

    Efficient and economic DNA nanomaterials that can work as logic components are necessary for the development of DNA computers with high speed and outstanding data storage capacity. A new molecular catalytic beacon (MCB) and a series of label-free colorimetric logic gates based on the formation and dissociation of G-quadruplex DNAzyme were established in this work. These logic gates (NOT, NOR, IMPLICATION, AND, OR and INHIBIT) were realized by the interaction between the special designed oligonucleotide hairpins and the short input single strand complementary DNA. We were able to recognize the logic output signals effortlessly by our naked eyes. It is a simple, economic and safe approach for the design of complex multiple input DNA logic molecular device.

  5. High-resolution mesoscopic fluorescence molecular tomography based on compressive sensing.

    PubMed

    Yang, Fugang; Ozturk, Mehmet S; Zhao, Lingling; Cong, Wenxiang; Wang, Ge; Intes, Xavier

    2015-01-01

    Mesoscopic fluorescence molecular tomography (MFMT) is new imaging modality aiming at 3-D imaging of molecular probes in a few millimeter thick biological samples with high-spatial resolution. In this paper, we develop a compressive sensing-based reconstruction method with l1-norm regularization for MFMT with the goal of improving spatial resolution and stability of the optical inverse problem. Three-dimensional numerical simulations of anatomically accurate microvasculature and real data obtained from phantom experiments are employed to evaluate the merits of the proposed method. Experimental results show that the proposed method can achieve 80 μm spatial resolution for a biological sample of 3 mm thickness and more accurate quantifications of concentrations and locations for the fluorophore distribution than those of the conventional methods.

  6. A survey of molecular descriptors used in mass spectrometry based proteomics.

    PubMed

    Audain, Enrique; Sanchez, Aniel; Vizcaíno, Juan Antonio; Perez-Riverol, Yasset

    2014-01-01

    The field of proteomics has grown vertiginously in the last years. This has been due fundamentally to technological improvements in the instrumentation, methods, and easy-to-use software, thereby making it possible to address a large number of biological questions and to deepen the study of the proteome of several organisms. The development in the field has imposed a challenge in the computational analysis of the commonly obtained large datasets generated in a single proteomics experiment, which still remains. An alternative to tackle this general issue has been the use of auxiliary information generated during the proteomics experiment to validate the confidence of the identifications. In this manuscript we review the main molecular descriptors used for building predictor models for estimating retention time, isoelectric point and peptide "detectability", which are key tools in the design of several validation strategies based in these criteria. We also give an overview of the main open source tools and libraries used for computing molecular descriptors.

  7. Surface plasmon resonance based optical fiber riboflavin sensor by using molecularly imprinted gel

    NASA Astrophysics Data System (ADS)

    Verma, Roli; Gupta, Banshi D.

    2013-05-01

    We report the fabrication and characterization of surface plasmon resonance (SPR) based optical fiber riboflavin/vitamin B2 sensor using combination of colloidal crystal templating and molecularly imprinted gel. The sensor works on spectral interrogation method. The operating range of the sensor lies from 0 μg/ml to 320 μg/ml, the suitable amount of intakes of riboflavin recommended for different age group. The SPR spectra show blue shift with increasing concentration of riboflavin, which is due to the interaction of riboflavin molecule over specific binding sites caused by molecular imprinting. The present sensor has many advantageous features such as fast response, small probe size, low cost and can be used for remote/online monitoring.

  8. Molecular diversification of Trichuris spp. from Sigmodontinae (Cricetidae) rodents from Argentina based on mitochondrial DNA sequences.

    PubMed

    Callejón, Rocío; Robles, María Del Rosario; Panei, Carlos Javier; Cutillas, Cristina

    2016-08-01

    A molecular phylogenetic hypothesis is presented for the genus Trichuris based on sequence data from mitochondrial cytochrome c oxidase 1 (cox1) and cytochrome b (cob). The taxa consisted of nine populations of whipworm from five species of Sigmodontinae rodents from Argentina. Bayesian Inference, Maximum Parsimony, and Maximum Likelihood methods were used to infer phylogenies for each gene separately but also for the combined mitochondrial data and the combined mitochondrial and nuclear dataset. Phylogenetic results based on cox1 and cob mitochondrial DNA (mtDNA) revealed three clades strongly resolved corresponding to three different species (Trichuris navonae, Trichuris bainae, and Trichuris pardinasi) showing phylogeographic variation, but relationships among Trichuris species were poorly resolved. Phylogenetic reconstruction based on concatenated sequences had greater phylogenetic resolution for delimiting species and populations intra-specific of Trichuris than those based on partitioned genes. Thus, populations of T. bainae and T. pardinasi could be affected by geographical factors and co-divergence parasite-host. PMID:27083190

  9. Molecular thermodynamic modeling of ionic liquids using the perturbation-based linear Yukawa isotherm regularity

    NASA Astrophysics Data System (ADS)

    Sohrabi Mahboub, Mahdi; Farrokhpour, Hossein

    2016-06-01

    In this paper, we present the results of an extensive study on a novel approach to the molecular modeling of pure ionic liquids (ILs) that incorporates the perturbed thermodynamic linear Yukawa isotherm regularity (LYIR), which is derived based on an effective nearest neighboring pair attractive interaction of the Yukawa potential. The LYIR was used to model the densities of ILs up to high pressures (35 MPa) and in the temperature range 293.15 to 393.15 K. To use the LYIR for ILs, a simple molecular model was proposed to describe their molecular structure, in which they were considered as a liquid consisting of the ion pairs moving together in the fluid, and each ion pair was assumed to be a one-center spherical united atom. The ILs under consideration contained one of the IL cations [C2mim]+, [C4mim]+, [C7mim]+, [C8mim]+, [C3mpy]+, [C3mpip]+, [C3mpyr]+ or [C4mpyr]+, and one of the IL anions [BF4]-, [C(CN)3]-, [CF3SO4]- or [NTf2]-. The reliability and physical significance of the parameters as well as the proposed molecular model were tested by calculating the densities of pure imidazolium-, pyridinium-, piperidinium- and pyrrolidimium-based ILs. The results showed that the LYIR can be used to predict and reproduce the density of ILs in good agreement with the experimental data. In addition, the LYIR enabled us to determine the physical quantities, such as an effective Yukawa screening length, λ eff, the product of the effective energy well depth and the effective coordination number, (ɛ eff/k)z eff, the contribution of the non-reference thermal pressure and also the influence of the anionic and cationic structure on the λ eff parameter. The standard deviation of the IL densities predicted in this work is lower than those calculated by the one other important equation of state reported in the literature.

  10. Shape-based virtual screening, docking, and molecular dynamics simulations to identify Mtb-ASADH inhibitors.

    PubMed

    Kumar, Rajender; Garg, Prabha; Bharatam, P V

    2015-01-01

    Aspartate β-semialdehyde dehydrogenase (ASADH) is a key enzyme for the biosynthesis of essential amino acids and several important metabolites in microbes. Inhibition of ASADH enzyme is a promising drug target strategy against Mycobacterium tuberculosis (Mtb). In this work, in silico approach was used to identify potent inhibitors of Mtb-ASADH. Aspartyl β-difluorophosphonate (β-AFP), a known lead compound, was used to understand the molecular recognition interactions (using molecular docking and molecular dynamics analysis). This analysis helped in validating the computational protocol and established the participation of Arg99, Glu224, Cys130, Arg249, and His256 amino acids as the key amino acids in stabilizing ligand-enzyme interactions for effective binding, an essential feature is H-bonding interactions with the two arginyl residues at the two ends of the ligand. Best binding conformation of β-AFP was selected as a template for shape-based virtual screening (ZINC and NCI databases) to identify compounds that competitively inhibit the Mtb-ASADH. The top rank hits were further subjected to ADME and toxicity filters. Final filter was based on molecular docking analysis. Each screened molecule carries the characteristics of the highly electronegative groups on both sides separated by an average distance of 6 Å. Finally, the best predicted 20 compounds exhibited minimum three H-bonding interactions with Arg99 and Arg249. These identified hits can be further used for designing the more potent inhibitors against ASADH family. MD simulations were also performed on two selected compounds (NSC4862 and ZINC02534243) for further validation. During the MD simulations, both compounds showed same H-bonding interactions and remained bound to key active residues of Mtb-ASADH.

  11. A Phylogeny of the Family Poritidae (Cnidaria, Scleractinia) Based on Molecular and Morphological Analyses

    PubMed Central

    Kitano, Yuko F.; Benzoni, Francesca; Arrigoni, Roberto; Shirayama, Yoshihisa; Wallace, Carden C.; Fukami, Hironobu

    2014-01-01

    The family Poritidae formerly included 6 genera: Alveopora, Goniopora, Machadoporites, Porites, Poritipora, and Stylaraea. Morphologically, the genera can be differentiated based on the number of tentacles, the number of septa and their arrangement, the length of the polyp column, and the diameter of the corallites. However, the phylogenetic relationships within and between the genera are unknown or contentious. On the one hand, Alveopora has been transferred to the Acroporidae recently because it was shown to be more closely related to this family than to the Poritidae by previous molecular studies. On the other hand, Goniopora is morphologically similar to 2 recently described genera, Machadoporites and Poritipora, particularly with regard to the number of septa (approximately 24), but they have not yet been investigated at the molecular level. In this study, we analyzed 93 samples from all 5 poritid genera and Alveopora using 2 genetic markers (the barcoding region of the mitochondrial COI and the ITS region of the nuclear rDNA) to investigate their phylogenetic relationships and to revise their taxonomy. The reconstructed molecular trees confirmed that Alveopora is genetically distant from all poritid genera but closely related to the family Acroporidae, whereas the other genera are genetically closely related. The molecular trees also revealed that Machadoporites and Poritipora were indistinguishable from Goniopora. However, Goniopora stutchburyi was genetically isolated from the other congeneric species and formed a sister group to Goniopora together with Porites and Stylaraea, thus suggesting that 24 septa could be an ancestral feature in the Poritidae. Based on these data, we move G. stutchburyi into a new genus, Bernardpora gen. nov., whereas Machadoporites and Poritipora are merged with Goniopora. PMID:24871224

  12. A molecular beacon-based DNA switch for reversible pH sensing in vesicles and live cells.

    PubMed

    Narayanaswamy, Nagarjun; Nair, Raji R; Suseela, Y V; Saini, Deepak Kumar; Govindaraju, T

    2016-07-01

    In this Communication, a molecular beacon-based DNA switch (LMB) is developed as an efficient and reversible pH sensing probe. Remarkably, LMB exhibited reversible structural transition between the closed (molecular beacon) and open (A-motif) states very efficiently in synthetic vesicles and live cells without the need for any transfection agents. PMID:27338808

  13. A molecular beacon-based DNA switch for reversible pH sensing in vesicles and live cells.

    PubMed

    Narayanaswamy, Nagarjun; Nair, Raji R; Suseela, Y V; Saini, Deepak Kumar; Govindaraju, T

    2016-07-01

    In this Communication, a molecular beacon-based DNA switch (LMB) is developed as an efficient and reversible pH sensing probe. Remarkably, LMB exhibited reversible structural transition between the closed (molecular beacon) and open (A-motif) states very efficiently in synthetic vesicles and live cells without the need for any transfection agents.

  14. An aptazyme-based molecular device that converts a small-molecule input into an RNA output.

    PubMed

    Ayukawa, Shotaro; Sakai, Yoko; Kiga, Daisuke

    2012-08-01

    We describe the construction of an aptazyme-based molecular device that converts, through a cascade of reactions, a small-molecule input into output RNA strands. This device is applicable as an interface between a small molecule and a molecular system that accepts only nucleic acid input.

  15. Molecular classification based on apomorphic amino acids (Arthropoda, Hexapoda): Integrative taxonomy in the era of phylogenomics

    PubMed Central

    Wu, Hao-Yang; Wang, Yan-Hui; Xie, Qiang; Ke, Yun-Ling; Bu, Wen-Jun

    2016-01-01

    With the great development of sequencing technologies and systematic methods, our understanding of evolutionary relationships at deeper levels within the tree of life has greatly improved over the last decade. However, the current taxonomic methodology is insufficient to describe the growing levels of diversity in both a standardised and general way due to the limitations of using only morphological traits to describe clades. Herein, we propose the idea of a molecular classification based on hierarchical and discrete amino acid characters. Clades are classified based on the results of phylogenetic analyses and described using amino acids with group specificity in phylograms. Practices based on the recently published phylogenomic datasets of insects together with 15 de novo sequenced transcriptomes in this study demonstrate that such a methodology can accommodate various higher ranks of taxonomy. Such an approach has the advantage of describing organisms in a standard and discrete way within a phylogenetic framework, thereby facilitating the recognition of clades from the view of the whole lineage, as indicated by PhyloCode. By combining identification keys and phylogenies, the molecular classification based on hierarchical and discrete characters may greatly boost the progress of integrative taxonomy. PMID:27312960

  16. High performance computing for three-dimensional agent-based molecular models.

    PubMed

    Pérez-Rodríguez, G; Pérez-Pérez, M; Fdez-Riverola, F; Lourenço, A

    2016-07-01

    Agent-based simulations are increasingly popular in exploring and understanding cellular systems, but the natural complexity of these systems and the desire to grasp different modelling levels demand cost-effective simulation strategies and tools. In this context, the present paper introduces novel sequential and distributed approaches for the three-dimensional agent-based simulation of individual molecules in cellular events. These approaches are able to describe the dimensions and position of the molecules with high accuracy and thus, study the critical effect of spatial distribution on cellular events. Moreover, two of the approaches allow multi-thread high performance simulations, distributing the three-dimensional model in a platform independent and computationally efficient way. Evaluation addressed the reproduction of molecular scenarios and different scalability aspects of agent creation and agent interaction. The three approaches simulate common biophysical and biochemical laws faithfully. The distributed approaches show improved performance when dealing with large agent populations while the sequential approach is better suited for small to medium size agent populations. Overall, the main new contribution of the approaches is the ability to simulate three-dimensional agent-based models at the molecular level with reduced implementation effort and moderate-level computational capacity. Since these approaches have a generic design, they have the major potential of being used in any event-driven agent-based tool. PMID:27372059

  17. High performance computing for three-dimensional agent-based molecular models.

    PubMed

    Pérez-Rodríguez, G; Pérez-Pérez, M; Fdez-Riverola, F; Lourenço, A

    2016-07-01

    Agent-based simulations are increasingly popular in exploring and understanding cellular systems, but the natural complexity of these systems and the desire to grasp different modelling levels demand cost-effective simulation strategies and tools. In this context, the present paper introduces novel sequential and distributed approaches for the three-dimensional agent-based simulation of individual molecules in cellular events. These approaches are able to describe the dimensions and position of the molecules with high accuracy and thus, study the critical effect of spatial distribution on cellular events. Moreover, two of the approaches allow multi-thread high performance simulations, distributing the three-dimensional model in a platform independent and computationally efficient way. Evaluation addressed the reproduction of molecular scenarios and different scalability aspects of agent creation and agent interaction. The three approaches simulate common biophysical and biochemical laws faithfully. The distributed approaches show improved performance when dealing with large agent populations while the sequential approach is better suited for small to medium size agent populations. Overall, the main new contribution of the approaches is the ability to simulate three-dimensional agent-based models at the molecular level with reduced implementation effort and moderate-level computational capacity. Since these approaches have a generic design, they have the major potential of being used in any event-driven agent-based tool.

  18. Molecular classification based on apomorphic amino acids (Arthropoda, Hexapoda): Integrative taxonomy in the era of phylogenomics.

    PubMed

    Wu, Hao-Yang; Wang, Yan-Hui; Xie, Qiang; Ke, Yun-Ling; Bu, Wen-Jun

    2016-06-17

    With the great development of sequencing technologies and systematic methods, our understanding of evolutionary relationships at deeper levels within the tree of life has greatly improved over the last decade. However, the current taxonomic methodology is insufficient to describe the growing levels of diversity in both a standardised and general way due to the limitations of using only morphological traits to describe clades. Herein, we propose the idea of a molecular classification based on hierarchical and discrete amino acid characters. Clades are classified based on the results of phylogenetic analyses and described using amino acids with group specificity in phylograms. Practices based on the recently published phylogenomic datasets of insects together with 15 de novo sequenced transcriptomes in this study demonstrate that such a methodology can accommodate various higher ranks of taxonomy. Such an approach has the advantage of describing organisms in a standard and discrete way within a phylogenetic framework, thereby facilitating the recognition of clades from the view of the whole lineage, as indicated by PhyloCode. By combining identification keys and phylogenies, the molecular classification based on hierarchical and discrete characters may greatly boost the progress of integrative taxonomy.

  19. Molecularly imprinted microparticles in lipid-based formulations for sustained release of donepezil.

    PubMed

    Ruela, André Luís Morais; de Figueiredo, Eduardo Costa; de Araújo, Magali Benjamim; Carvalho, Flávia Chiva; Pereira, Gislaine Ribeiro

    2016-10-10

    Donepezil is a drug administered for Alzheimer's disease treatment, and it is a potential template molecule for imprinted microparticles. The precipitation polymerization technique allows the synthesis of spherical imprinted microparticles, and the intermolecular interactions among drug and molecularly imprinted polymers (MIPs) play a promising role for delineating drug delivery systems. Once that donepezil is a poorly-water soluble compound, lipid based-formulations (LBFs) may enhance its oral administration. Based on this, LBFs are useful vehicles to incorporate imprinted microparticles synthesized by precipitation polymerization. In these formulations, the drug dissolved in lipids is accessible to adsorbate in the polymers, and the hydrophobic environment of lipids increases the molecular recognition of MIPs. The formulations based on MIPs using pure oleic acid as vehicle prolong the in vitro release of donepezil up to several hours by a Fickian diffusion mechanism, and it provides a multiphasic release pattern related to the heterogeneity of the binding sites. The modulation of donepezil release from MIPs-based formulations using oil vehicles may contribute to decrease its side effects, possibly regulating its absorption rate in the gastrointestinal tract. These systems represent a novel technological platform to prolong the delivery not only for donepezil, but also for a variety of therapeutics.

  20. Molecular profiling for genetic variability in Capsicum species based on ISSR and RAPD markers.

    PubMed

    Thul, Sanjog T; Darokar, Mahendra P; Shasany, Ajit K; Khanuja, Suman P S

    2012-06-01

    The taxonomic identity of Capsicum species is found to be difficult as it displays variations at morpho-chemical characters. Twenty-two accessions of six Capsicum species, namely, C. annuum, C. baccatum, C. chinense, C. eximium, C. frutescens, and C. luteum were investigated for phenotypic diversity based on flower color and for genetic differences by molecular makers. The genetic cluster analyses of 27 RAPD and eight ISSR primers, respectively, revealed genetic similarities in the ranges of 23-88% and 11-96%. Principal component analysis of the pooled RAPD and ISSR data further supports the genetic similarity and groupings. Different species showed variations in relation to corolla shade of flower. C. annuum accessions formed a single cluster in the molecular analysis as maintaining their flower characteristic. C. chinense accession shared flower features with the accessions of C. frutescens and were found to be closer at genotypic level. C. luteum was found to be rather closer to C. baccatum complex, both phenotypically and genetically. The only accession of C. eximium presenting purple flowers falls apart from the groupings. The floral characteristics and the molecular markers are found to be useful toward the delineation of the species specificity in Capsicum collection and identification of genetic stock.

  1. A nitrogen-vacancy spin based molecular structure microscope using multiplexed projection reconstruction

    NASA Astrophysics Data System (ADS)

    Lazariev, Andrii; Balasubramanian, Gopalakrishnan

    2015-09-01

    Methods and techniques to measure and image beyond the state-of-the-art have always been influential in propelling basic science and technology. Because current technologies are venturing into nanoscopic and molecular-scale fabrication, atomic-scale measurement techniques are inevitable. One such emerging sensing method uses the spins associated with nitrogen-vacancy (NV) defects in diamond. The uniqueness of this NV sensor is its atomic size and ability to perform precision sensing under ambient conditions conveniently using light and microwaves (MW). These advantages have unique applications in nanoscale sensing and imaging of magnetic fields from nuclear spins in single biomolecules. During the last few years, several encouraging results have emerged towards the realization of an NV spin-based molecular structure microscope. Here, we present a projection-reconstruction method that retrieves the three-dimensional structure of a single molecule from the nuclear spin noise signatures. We validate this method using numerical simulations and reconstruct the structure of a molecular phantom β-cyclodextrin, revealing the characteristic toroidal shape.

  2. Quantitative Description of a Protein Fitness Landscape Based on Molecular Features.

    PubMed

    Meini, María-Rocío; Tomatis, Pablo E; Weinreich, Daniel M; Vila, Alejandro J

    2015-07-01

    Understanding the driving forces behind protein evolution requires the ability to correlate the molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study of all the possible evolutionary pathways leading to a metallo-β-lactamase variant optimized by directed evolution. By studying the activity, stability and Zn(II) binding capabilities of all mutants in the preferred evolutionary pathways, we show that this local fitness landscape is strongly conditioned by epistatic interactions arising from the pleiotropic effect of mutations in the different molecular features of the enzyme. Activity and stability assays in purified enzymes do not provide explanatory power. Instead, measurement of these molecular features in an environment resembling the native one provides an accurate description of the observed antibiotic resistance profile. We report that optimization of Zn(II) binding abilities of metallo-β-lactamases during evolution is more critical than stabilization of the protein to enhance fitness. A global analysis of these parameters allows us to connect genotype with fitness based on quantitative biochemical and biophysical parameters.

  3. Sensor Based on Aptamer Folding to Detect Low-Molecular Weight Analytes.

    PubMed

    Osypova, Alina; Thakar, Dhruv; Dejeu, Jérôme; Bonnet, Hugues; Van der Heyden, Angéline; Dubacheva, Galina V; Richter, Ralf P; Defrancq, Eric; Spinelli, Nicolas; Coche-Guérente, Liliane; Labbé, Pierre

    2015-08-01

    Aptamers have emerged as promising biorecognition elements in the development of biosensors. The present work focuses on the application of quartz crystal microbalance with dissipation monitoring (QCM-D) for the enantioselective detection of a low molecular weight target molecule (less than 200 Da) by aptamer-based sensors. While QCM-D is a powerful technique for label-free, real-time characterization and quantification of molecular interactions at interfaces, the detection of small molecules interacting with immobilized receptors still remains a challenge. In the present study, we take advantage of the aptamer conformational changes upon the target binding that induces displacement of water acoustically coupled to the sensing layer. As a consequence, this phenomenon leads to a significant enhancement of the detection signal. The methodology is exemplified with the enantioselective recognition of a low molecular weight model compound, L-tyrosinamide (L-Tym). QCM-D monitoring of L-Tym interaction with the aptamer monolayer leads to an appreciable signal that can be further exploited for analytical purposes or thermodynamics studies. Furthermore, in situ combination of QCM-D with spectroscopic ellipsometry unambiguously demonstrates that the conformational change induces a nanometric decrease of the aptamer monolayer thickness. Since QCM-D is sensitive to the whole mass of the sensing layer including water that is acoustically coupled, a decrease in thickness of the highly hydrated aptamer layer induces a sizable release of water that can be easily detected by QCM-D. PMID:26122480

  4. "Molecular beacon"-based fluorescent assay for selective detection of glutathione and cysteine.

    PubMed

    Xu, Hui; Hepel, Maria

    2011-02-01

    We report on the development of a fluorescence turn-on "molecular beacon" probe for the detection of glutathione (GSH) and cysteine (Cys). The method is based on a competitive ligation of Hg(2+) ions by GSH/Cys and thymine-thymine (T-T) mismatches in a DNA strand of the self-hybridizing beacon strand. The assay relies on the distance-dependent optical properties of the fluorophore/quencher pair attached to the ends of the molecular beacon DNA strand. In a very selective coordination of Hg(2+) to GSH/Cys, the fluorophore/quencher distance increases concomitantly with the dehybridization and dissociation of the beacon stem T-Hg(2+)-T due to the extraction of Hg(2+) ions. This process results in switching the molecular beacon to the "on" state. The concentration range of the probe is 4-200 nM with the limit of detection (LOD) of 4.1 nM for GSH and 4.2 nM Cys. The probe tested satisfactorily against interference for a range of amino acids including sulfur-containing methionine.

  5. Low-molecular-weight polyethylenimine enhanced gene transfer by cationic cholesterol-based nanoparticle vector.

    PubMed

    Hattori, Yoshiyuki; Maitani, Yoshie

    2007-09-01

    Both polyethylenimine (PEI) polymers and cationic nanoparticles have been widely used for non-viral DNA transfection. Previously, we reported that cationic nanoparticles composed of cholesteryl-3beta-carboxyamidoethylene-N-hydroxyethylamine and Tween 80 (NP-OH) could deliver plasmid DNA (pDNA) with high transfection efficiency. To increase the transfection activity of NP-OH, we investigated the potential synergism of PEI and NP-OH for the transfection of DNA into human prostate tumor PC-3, human cervices tumor Hela, and human lung adenocarcinoma A549 cells. The transfection efficiency with low-molecular PEI (MW 600) was low, but that with a combination of NP-OH and PEI was higher than with NP-OH alone, being comparable to commercially available lipofectamine 2,000 and lipofectamine LTX, with very low cytotoxicity. Low-molecular weight PEI could not compact pDNA in size, but rather might help to dissociate pDNA from the complex and release pDNA from the endosome to cytoplasm by the proton sponge effect. Therefore, the combination of cationic cholesterol-based nanoparticles and a low-molecular PEI has potential as a non-viral DNA vector for gene delivery.

  6. A nitrogen-vacancy spin based molecular structure microscope using multiplexed projection reconstruction

    PubMed Central

    Lazariev, Andrii; Balasubramanian, Gopalakrishnan

    2015-01-01

    Methods and techniques to measure and image beyond the state-of-the-art have always been influential in propelling basic science and technology. Because current technologies are venturing into nanoscopic and molecular-scale fabrication, atomic-scale measurement techniques are inevitable. One such emerging sensing method uses the spins associated with nitrogen-vacancy (NV) defects in diamond. The uniqueness of this NV sensor is its atomic size and ability to perform precision sensing under ambient conditions conveniently using light and microwaves (MW). These advantages have unique applications in nanoscale sensing and imaging of magnetic fields from nuclear spins in single biomolecules. During the last few years, several encouraging results have emerged towards the realization of an NV spin-based molecular structure microscope. Here, we present a projection-reconstruction method that retrieves the three-dimensional structure of a single molecule from the nuclear spin noise signatures. We validate this method using numerical simulations and reconstruct the structure of a molecular phantom β-cyclodextrin, revealing the characteristic toroidal shape. PMID:26370514

  7. Sensor Based on Aptamer Folding to Detect Low-Molecular Weight Analytes.

    PubMed

    Osypova, Alina; Thakar, Dhruv; Dejeu, Jérôme; Bonnet, Hugues; Van der Heyden, Angéline; Dubacheva, Galina V; Richter, Ralf P; Defrancq, Eric; Spinelli, Nicolas; Coche-Guérente, Liliane; Labbé, Pierre

    2015-08-01

    Aptamers have emerged as promising biorecognition elements in the development of biosensors. The present work focuses on the application of quartz crystal microbalance with dissipation monitoring (QCM-D) for the enantioselective detection of a low molecular weight target molecule (less than 200 Da) by aptamer-based sensors. While QCM-D is a powerful technique for label-free, real-time characterization and quantification of molecular interactions at interfaces, the detection of small molecules interacting with immobilized receptors still remains a challenge. In the present study, we take advantage of the aptamer conformational changes upon the target binding that induces displacement of water acoustically coupled to the sensing layer. As a consequence, this phenomenon leads to a significant enhancement of the detection signal. The methodology is exemplified with the enantioselective recognition of a low molecular weight model compound, L-tyrosinamide (L-Tym). QCM-D monitoring of L-Tym interaction with the aptamer monolayer leads to an appreciable signal that can be further exploited for analytical purposes or thermodynamics studies. Furthermore, in situ combination of QCM-D with spectroscopic ellipsometry unambiguously demonstrates that the conformational change induces a nanometric decrease of the aptamer monolayer thickness. Since QCM-D is sensitive to the whole mass of the sensing layer including water that is acoustically coupled, a decrease in thickness of the highly hydrated aptamer layer induces a sizable release of water that can be easily detected by QCM-D.

  8. Label-Free Sensing of Adenosine Based on Force Variations Induced by Molecular Recognition

    PubMed Central

    Li, Jingfeng; Li, Qing; Colombi Ciacchi, Lucio; Wei, Gang

    2015-01-01

    We demonstrate a simple force-based label-free strategy for the highly sensitive sensing of adenosine. An adenosine ssDNA aptamer was bound onto an atomic force microscopy (AFM) probe by covalent modification, and the molecular-interface adsorption force between the aptamer and a flat graphite surface was measured by single-molecule force spectroscopy (SMFS). In the presence of adenosine, the molecular recognition between adenosine and the aptamer resulted in the formation of a folded, hairpin-like DNA structure and hence caused a variation of the adsorption force at the graphite/water interface. The sensitive force response to molecular recognition provided an adenosine detection limit in the range of 0.1 to 1 nM. The addition of guanosine, cytidine, and uridine had no significant interference with the sensing of adenosine, indicating a strong selectivity of this sensor architecture. In addition, operational parameters that may affect the sensor, such as loading rate and solution ionic strength, were investigated. PMID:25808841

  9. Quantitative Description of a Protein Fitness Landscape Based on Molecular Features

    PubMed Central

    Meini, María-Rocío; Tomatis, Pablo E.; Weinreich, Daniel M.; Vila, Alejandro J.

    2015-01-01

    Understanding the driving forces behind protein evolution requires the ability to correlate the molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study of all the possible evolutionary pathways leading to a metallo-β-lactamase variant optimized by directed evolution. By studying the activity, stability and Zn(II) binding capabilities of all mutants in the preferred evolutionary pathways, we show that this local fitness landscape is strongly conditioned by epistatic interactions arising from the pleiotropic effect of mutations in the different molecular features of the enzyme. Activity and stability assays in purified enzymes do not provide explanatory power. Instead, measurement of these molecular features in an environment resembling the native one provides an accurate description of the observed antibiotic resistance profile. We report that optimization of Zn(II) binding abilities of metallo-β-lactamases during evolution is more critical than stabilization of the protein to enhance fitness. A global analysis of these parameters allows us to connect genotype with fitness based on quantitative biochemical and biophysical parameters. PMID:25767204

  10. Label-free sensing of adenosine based on force variations induced by molecular recognition.

    PubMed

    Li, Jingfeng; Li, Qing; Ciacchi, Lucio Colombi; Wei, Gang

    2015-03-01

    We demonstrate a simple force-based label-free strategy for the highly sensitive sensing of adenosine. An adenosine ssDNA aptamer was bound onto an atomic force microscopy (AFM) probe by covalent modification, and the molecular-interface adsorption force between the aptamer and a flat graphite surface was measured by single-molecule force spectroscopy (SMFS). In the presence of adenosine, the molecular recognition between adenosine and the aptamer resulted in the formation of a folded, hairpin-like DNA structure and hence caused a variation of the adsorption force at the graphite/water interface. The sensitive force response to molecular recognition provided an adenosine detection limit in the range of 0.1 to 1 nM. The addition of guanosine, cytidine, and uridine had no significant interference with the sensing of adenosine, indicating a strong selectivity of this sensor architecture. In addition, operational parameters that may affect the sensor, such as loading rate and solution ionic strength, were investigated.

  11. Quantitative Description of a Protein Fitness Landscape Based on Molecular Features.

    PubMed

    Meini, María-Rocío; Tomatis, Pablo E; Weinreich, Daniel M; Vila, Alejandro J

    2015-07-01

    Understanding the driving forces behind protein evolution requires the ability to correlate the molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study of all the possible evolutionary pathways leading to a metallo-β-lactamase variant optimized by directed evolution. By studying the activity, stability and Zn(II) binding capabilities of all mutants in the preferred evolutionary pathways, we show that this local fitness landscape is strongly conditioned by epistatic interactions arising from the pleiotropic effect of mutations in the different molecular features of the enzyme. Activity and stability assays in purified enzymes do not provide explanatory power. Instead, measurement of these molecular features in an environment resembling the native one provides an accurate description of the observed antibiotic resistance profile. We report that optimization of Zn(II) binding abilities of metallo-β-lactamases during evolution is more critical than stabilization of the protein to enhance fitness. A global analysis of these parameters allows us to connect genotype with fitness based on quantitative biochemical and biophysical parameters. PMID:25767204

  12. Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay

    PubMed Central

    Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

    2016-01-01

    This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF-7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot-based molecular targeted imaging techniques (which stained pan-cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF-7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot-based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology. PMID:27572664

  13. Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

    PubMed

    Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

    2016-10-01

    This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

  14. Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

    PubMed

    Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

    2016-10-01

    This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology. PMID:27572664

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

    PubMed

    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.

  16. Synthesis of molecular complexes based on porphyrins for the investigation of the energy transfer and primary charge separation in photosynthesis

    NASA Astrophysics Data System (ADS)

    Gribkova, S. E.; Evstigneeva, Rima P.; Luzgina, Valentina N.

    1993-10-01

    Data on the synthesis, steric structures, and photochemical properties of molecular diad systems based on porphyrins as synthetic models of the reaction centre in photosynthesis are considered and treated systematically. The bibliography includes 102 references.

  17. Mass Spectrometry-Based Approaches to Understand the Molecular Basis of Memory

    PubMed Central

    Pontes, Arthur H.; de Sousa, Marcelo V.

    2016-01-01

    The central nervous system is responsible for an array of cognitive functions such as memory, learning, language, and attention. These processes tend to take place in distinct brain regions; yet, they need to be integrated to give rise to adaptive or meaningful behavior. Since cognitive processes result from underlying cellular and molecular changes, genomics and transcriptomics assays have been applied to human and animal models to understand such events. Nevertheless, genes and RNAs are not the end products of most biological functions. In order to gain further insights toward the understanding of brain processes, the field of proteomics has been of increasing importance in the past years. Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS) have enabled the identification and quantification of thousands of proteins with high accuracy and sensitivity, fostering a revolution in the neurosciences. Herein, we review the molecular bases of explicit memory in the hippocampus. We outline the principles of mass spectrometry (MS)-based proteomics, highlighting the use of this analytical tool to study memory formation. In addition, we discuss MS-based targeted approaches as the future of protein analysis. PMID:27790611

  18. AOTF based molecular hyperspectral imaging system and its applications on nerve morphometry.

    PubMed

    Li, Qingli; Xu, Dongrong; He, Xiaofu; Wang, Yiting; Chen, Zenggan; Liu, Hongying; Xu, Qintong; Guo, Fangmin

    2013-06-10

    The neuroanatomical morphology of nerve fibers is an important description for understanding the pathological aspects of nerves. Different from the traditional automatic nerve morphometry methods, a molecular hyperspectral imaging system based on an acousto-optic tunable filter (AOTF) was developed and used to identify unstained nerve histological sections. The hardware, software, and system performance of the imaging system are presented and discussed. The gray correction coefficient was used to calibrate the system's spectral response and to remove the effects of noises and artifacts. A spatial-spectral kernel-based approach through the support vector machine formulation was proposed to identify nerve fibers. This algorithm can jointly use both the spatial and spectral information of molecular hyperspectral images for segmentation. Then, the morphological parameters such as fiber diameter, axon diameter, myelin sheath thickness, fiber area, and g-ratio were calculated and evaluated. Experimental results show that the hyperspectral-based method has the potential to recognize and measure the nerve fiber more accurately than traditional methods. PMID:23759836

  19. Zeolite molecular sieves have dramatic acid-base effects on enzymes in nonaqueous media.

    PubMed

    Fontes, Nuno; Partridge, Johann; Halling, Peter J; Barreiros, Susana

    2002-02-01

    Zeolite molecular sieves very commonly are used as in situ drying agents in reaction mixtures of enzymes in nonaqueous media. They often affect enzyme behavior, and this has been interpreted in terms of altered hydration. Here, we show that zeolites can also have dramatic acid-base effects on enzymes in low water media, resulting from their cation-exchange ability. Initial rates of transesterification catalyzed by cross-linked crystals of subtilisin were compared in supercritical ethane, hexane, and acetonitrile with water activity fixed by pre-equilibration. Addition of zeolite NaA (4 A powder) still caused remarkable rate enhancements (up to 20-fold), despite the separate control of hydration. In the presence of excess of an alternative solid-state acid-base buffer, however, zeolite addition had no effect. The more commonly used Merck molecular sieves (type 3 A beads) had similar but somewhat smaller effects. All zeolites have ion-exchange ability and can exchange H+ for cations such as Na+ and K+. These exchanges will tend to affect the protonation state of acidic groups in the protein and, hence, enzymatic activity. Zeolites pre-equilibrated in aqueous suspensions of varying pH-pNa gave very different enzyme activities. Their differing basicities were demonstrated directly by equilibration with an indicator dissolved in toluene. The potential of zeolites as acid-base buffers for low-water media is discussed, and their ability to overcome pH memory is demonstrated.

  20. Low molecular weight PEIs modified by hydrazone-based crosslinker and betaine as improved gene carriers.

    PubMed

    Fang, Gang; Zeng, Fang; Yu, Changmin; Wu, Shuizhu

    2014-10-01

    Low-molecular-weight polyethyleneimine (LMW PEI) exhibits poorer transfection efficiency but lower cytotoxicity compared to high-molecular-weight polyethyleneimine (such as PEI 25kDa). To enhance the gene transfection performance of LMW PEI, we herein demonstrate a new strategy for modifying LMW PEI. A crosslinker containing an acid-labile hydrazone bond (hydrazone-based crosslinker) was synthesized and used to crosslink PEI 1.8kDa and convert it into higher-molecular-weight polycations. And the crosslinked polycations were further modified by incorporating a betaine monomer [N,N-dimethyl(acrylamidopropyl)ammonium propane sulfonate, DMAAPS] onto their surfaces. The molar percentages of the incorporated betaine molecules to amino groups on the polycations were determined as 21.2%, 36.0% and 77.2%, respectively. Molecular weights of the modified polycations were measured using capillary viscometry at pH 7.4 and 5.0, respectively, and the degradation of the polymers in acidic solution was confirmed. The PEIs modified with hydrazone and betaine (PEI-Hdz-DMAAPS) exhibit much lower cytotoxicity than PEI 25K, and they also show no or little hemolytic effect with their hemolysis rates around 5%. PEI-Hdz-DMAAPS21.2%/DNA and PEI-Hdz-DMAAPS36.0%/DNA complexes exhibit high transfection efficiencies, which are comparable to or higher than that of PEI 25K/DNA complex in the absence or presence of 10% serum. With these improved gene delivery properties, the PEI-Hdz-DMAAPS samples have great potential for serving as efficient gene carriers. This strategy may provide some insights for constructing some other biocompatible materials.

  1. Monitoring molecular orientational order in NLO push-pull based polymeric films via photoacoustic measurements

    NASA Astrophysics Data System (ADS)

    Torres-Zúñiga, V.; Castañeda-Guzmán, R.; Morales-Saavedra, O. G.; Pérez-Martínez, A. L.; Ogawa, T.

    2011-12-01

    The pulsed-laser photoacoustic-technique (PLPA) was implemented to characterize molecular orientational order and anisotropy in push-pull poled polymeric films as function of temperature and laser polarization. Traditionally, photoacoustic signals are considered to be directly proportional to the linear optical absorption in amorphous media. In this work, however, it is shown that photoacoustic signals can also be highly sensitive to the material anisotropy when convenient polarization dependent photoacoustic analyses are performed. Thus, variation of the molecular orientation in organic films, comprising rod-like polar chromophores, can be unambiguously monitored via rms-analyses performed on the amplitude of the generated opto-acoustical PLPA-signals as function of the incident laser polarization. This result can be useful for the characterization of organic-based nonlinear optical (NLO) poled films and, in general, in studies of anisotropic materials. In fact, in this work we were able to accurately determine the molecular order parameter ( ϕ) of a NLO-active spin-coated polymeric film containing optically active push-pull chromophores. These molecules, previously oriented via an electrical-poling procedure, are capable to exhibit strong second harmonic generation (SHG) effects. The PLPA-measurements were systematically compared to the linear UV-vis optical absorbance spectra while heating the poled film sample in order to monitor the thermally induced molecular disorder, so that the order parameter may be photo-acoustically evaluated via the PLPA-signals generated from the poled to the unpoled film phase. These PLPA-experiments were performed taking into account the UV-vis reference spectra for calibration and comparison purposes in the evaluation of the order parameter. A significant advantage of the PLPA-technique over commonly used optical spectral methodologies is its convenient applicability in samples exhibiting poor or null optical transmission.

  2. A real-time proximity querying algorithm for haptic-based molecular docking.

    PubMed

    Iakovou, Georgios; Hayward, Steven; Laycock, Stephen

    2014-01-01

    Intermolecular binding underlies every metabolic and regulatory processes of the cell, and the therapeutic and pharmacological properties of drugs. Molecular docking systems model and simulate these interactions in silico and allow us to study the binding process. Haptic-based docking provides an immersive virtual docking environment where the user can interact with and guide the molecules to their binding pose. Moreover, it allows human perception, intuition and knowledge to assist and accelerate the docking process, and reduces incorrect binding poses. Crucial for interactive docking is the real-time calculation of interaction forces. For smooth and accurate haptic exploration and manipulation, force-feedback cues have to be updated at a rate of 1 kHz. Hence, force calculations must be performed within 1 ms. To achieve this, modern haptic-based docking approaches often utilize pre-computed force grids and linear interpolation. However, such grids are time-consuming to pre-compute (especially for large molecules), memory hungry, can induce rough force transitions at cell boundaries and cannot be applied to flexible docking. Here we propose an efficient proximity querying method for computing intermolecular forces in real time. Our motivation is the eventual development of a haptic-based docking solution that can model molecular flexibility. Uniquely in a haptics application we use octrees to decompose the 3D search space in order to identify the set of interacting atoms within a cut-off distance. Force calculations are then performed on this set in real time. The implementation constructs the trees dynamically, and computes the interaction forces of large molecular structures (i.e. consisting of thousands of atoms) within haptic refresh rates. We have implemented this method in an immersive, haptic-based, rigid-body, molecular docking application called Haptimol_RD. The user can use the haptic device to orientate the molecules in space, sense the interaction

  3. Liposome Formulation of Fullerene-Based Molecular Diagnostic and Therapeutic Agents

    PubMed Central

    Zhou, Zhiguo

    2013-01-01

    Fullerene medicine is a new but rapidly growing research subject. Fullerene has a number of desired structural, physical and chemical properties to be adapted for biological use including antioxidants, anti-aging, anti-inflammation, photodynamic therapy, drug delivery, and magnetic resonance imaging contrast agents. Chemical functionalization of fullerenes has led to several interesting compounds with very promising preclinical efficacy, pharmacokinetic and safety data. However, there is no clinical evaluation or human use except in fullerene-based cosmetic products for human skincare. This article summarizes recent advances in liposome formulation of fullerenes for the use in therapeutics and molecular imaging. PMID:24300561

  4. Framework for single input single output nanonetwork-based realistic molecular communication.

    PubMed

    Abd El-Atty, Saied M; Gharsseldien, Zakaria M; Lizos, Konstantinos A

    2015-12-01

    Mobile ad hoc molecular nanonetwork (MAMNET) is a new paradigm for the realisation of future nanonetworks. In MAMNET, transmission of nanoscale information from nanomachine to infostation is based on collision and adhesion. In this study, the authors develop a realistic framework for encompassing the electronic structure of the neurotransmitter in the process of transmitting nanoscale information at a single input single output nanonetwork. Nanonetwork performance is evaluated in terms of average packet delay, throughput and incurred traffic rate. Numerical results demonstrate the influence of the neurotransmitter's electronic structure over the performance of nanonetworks. PMID:26647808

  5. A description of the mechanical behavior of composite solid propellants based on molecular theory

    NASA Technical Reports Server (NTRS)

    Landel, R. F.

    1976-01-01

    Both the investigation and the representation of the stress-strain response (including rupture) of gum and filled elastomers can be based on a simple functional statement. Internally consistent experiments are used to sort out the effects of time, temperature, strain and crosslink density on gum rubbers. All effects are readily correlated and shown to be essentially independent of the elastomer when considered in terms of non-dimensionalized stress, strain and time. A semiquantitative molecular theory is developed to explain this result. The introduction of fillers modifies the response, but, guided by the framework thus provided, their effects can be readily accounted for.

  6. Noncontact full-angle fluorescence molecular tomography system based on rotary mirrors.

    PubMed

    Wang, Daifa; He, Jin; Qiao, Huiting; Li, Ping; Fan, Yubo; Li, Deyu

    2015-08-10

    We propose a novel noncontact fluorescence molecular tomography system that achieves full-angle capacity with the use of a new rotary-mirrors-based imaging head. In the imaging head, four plane mirrors are mounted on a rotating gantry to enable illumination and detection over 360°. In comparison with existing full-angle systems, our system does not require rotation of the specimen animal, a large and heavy light source (with scanning head), or a bulky camera (with filters and lens). The system design and implementation are described in detail. Both physical phantom and in vivo experiments are performed to verify the performance of the proposed system.

  7. Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

    PubMed Central

    Sterckx, Hans; De Houwer, Johan; Mensch, Carl; Herrebout, Wouter; Tehrani, Kourosch Abbaspour

    2016-01-01

    Summary The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP–MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit. PMID:26877817

  8. Physics-based protein structure refinement through multiple molecular dynamics trajectories and structure averaging.

    PubMed

    Mirjalili, Vahid; Noyes, Keenan; Feig, Michael

    2014-02-01

    We used molecular dynamics (MD) simulations for structure refinement of Critical Assessment of Techniques for Protein Structure Prediction 10 (CASP10) targets. Refinement was achieved by selecting structures from the MD-based ensembles followed by structural averaging. The overall performance of this method in CASP10 is described, and specific aspects are analyzed in detail to provide insight into key components. In particular, the use of different restraint types, sampling from multiple short simulations versus a single long simulation, the success of a quality assessment criterion, the application of scoring versus averaging, and the impact of a final refinement step are discussed in detail.

  9. Counterpoise-corrected interaction energy analysis based on the fragment molecular orbital scheme

    NASA Astrophysics Data System (ADS)

    Okiyama, Yoshio; Fukuzawa, Kaori; Yamada, Haruka; Mochizuki, Yuji; Nakano, Tatsuya; Tanaka, Shigenori

    2011-06-01

    Basis set superposition error (BSSE) correction with counterpoise (CP) procedure under the environmental electrostatic potential is newly introduced to interfragment interaction energy (IFIE), which is important for interaction analysis in the fragment molecular orbital method. The CP correction for IFIE is applied to a stacked dimer of base pair and a protein-ligand complex of estrogen receptor and 17β-estradiol with scaled third-order Møller-Plesset perturbation theory. The BSSEs amount to about quarter of IFIE for hydrogen-bonding and electrostatic interactions and half or even more for dispersion interactions. Estimation of IFIE with the CP correction is therefore preferred for the quantitative discussion.

  10. Framework for single input single output nanonetwork-based realistic molecular communication.

    PubMed

    Abd El-Atty, Saied M; Gharsseldien, Zakaria M; Lizos, Konstantinos A

    2015-12-01

    Mobile ad hoc molecular nanonetwork (MAMNET) is a new paradigm for the realisation of future nanonetworks. In MAMNET, transmission of nanoscale information from nanomachine to infostation is based on collision and adhesion. In this study, the authors develop a realistic framework for encompassing the electronic structure of the neurotransmitter in the process of transmitting nanoscale information at a single input single output nanonetwork. Nanonetwork performance is evaluated in terms of average packet delay, throughput and incurred traffic rate. Numerical results demonstrate the influence of the neurotransmitter's electronic structure over the performance of nanonetworks.

  11. Four- and five-component molecular solids: crystal engineering strategies based on structural inequivalence.

    PubMed

    Mir, Niyaz A; Dubey, Ritesh; Desiraju, Gautam R

    2016-03-01

    A synthetic strategy is described for the co-crystallization of four- and five-component molecular crystals, based on the fact that if any particular chemical constituent of a lower cocrystal is found in two different structural environments, these differences may be exploited to increase the number of components in the solid. 2-Methylresorcinol and tetramethylpyrazine are basic template molecules that allow for further supramolecular homologation. Ten stoichiometric quaternary cocrystals and one quintinary cocrystal with some solid solution character are reported. Cocrystals that do not lend themselves to such homologation are termed synthetic dead ends.

  12. Molecular Solid EOS based on Quasi-Harmonic Oscillator approximation for phonons

    SciTech Connect

    Menikoff, Ralph

    2014-09-02

    A complete equation of state (EOS) for a molecular solid is derived utilizing a Helmholtz free energy. Assuming that the solid is nonconducting, phonon excitations dominate the specific heat. Phonons are approximated as independent quasi-harmonic oscillators with vibrational frequencies depending on the specific volume. The model is suitable for calibrating an EOS based on isothermal compression data and infrared/Raman spectroscopy data from high pressure measurements utilizing a diamond anvil cell. In contrast to a Mie-Gruneisen EOS developed for an atomic solid, the specific heat and Gruneisen coefficient depend on both density and temperature.

  13. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps

    PubMed Central

    2013-01-01

    Background Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. Results NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. Conclusions NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps

  14. Synthesis, spectroscopic and molecular structures investigations of some carboxylated schiff bases

    NASA Astrophysics Data System (ADS)

    Titinchi, Salam J. J.; Abbo, Hanna S.; Saeed, Ali A. H.

    2004-11-01

    A series of nine carboxylated Schiff bases (five of them are newly prepared viz. compounds 5- 9), are prepared and characterized by various physico-chemical techniques. The molecular structures of synthesized Schiff bases are investigated by IR, UV-Visible, molar conductivities at different concentrations in two different solvents and by their pH values in ethanolic solutions. The IR spectra show absorptions due to = N⊕H- stretching and -N-H bending vibrations, the UV-Visible spectra indicates absorptions are due to protonated species. The molar conductivities, 0.1-0.6 Ω -1 cm 2 mol -1, prove that these compounds are weak electrolytes and are even weaker than tyrosine and phenylalanine, 2.5-13 Ω -1 cm 2 mol -1. The melting points and pH values of Schiff bases are compared with those of some α-aminoacids and some related Schiff bases that have no COOH group in their structures. On the bases of these data, it was concluded that carboxylated Schiff bases exist in two forms, the ionized and the free base where the later is predominant. The ionized form is similar to the zwitterion of the α-aminoacid, in which a proton is transferred from COOH to the azomethine (-CH dbnd6 N-) group.

  15. Conformations of flanking bases in HIV-1 RNA DIS kissing complexes studied by molecular dynamics.

    PubMed

    Réblová, Kamila; Fadrná, Eva; Sarzynska, Joanna; Kulinski, Tadeusz; Kulhánek, Petr; Ennifar, Eric; Koca, Jaroslav; Sponer, Jirí

    2007-12-01

    Explicit solvent molecular dynamics simulations (in total almost 800 ns including locally enhanced sampling runs) were applied with different ion conditions and with two force fields (AMBER and CHARMM) to characterize typical geometries adopted by the flanking bases in the RNA kissing-loop complexes. We focus on flanking base positions in multiple x-ray and NMR structures of HIV-1 DIS kissing complexes and kissing complex from the large ribosomal subunit of Haloarcula marismortui. An initial x-ray open conformation of bulged-out bases in HIV-1 DIS complexes, affected by crystal packing, tends to convert to a closed conformation formed by consecutive stretch of four stacked purine bases. This is in agreement with those recent crystals where the packing is essentially avoided. We also observed variants of the closed conformation with three stacked bases, while nonnegligible populations of stacked geometries with bulged-in bases were detected, too. The simulation results reconcile differences in positions of the flanking bases observed in x-ray and NMR studies. Our results suggest that bulged-out geometries are somewhat more preferred, which is in accord with recent experiments showing that they may mediate tertiary contacts in biomolecular assemblies or allow binding of aminoglycoside antibiotics.

  16. QTL Analysis of Head Splitting Resistance in Cabbage (Brassica oleracea L. var. capitata) Using SSR and InDel Makers Based on Whole-Genome Re-Sequencing

    PubMed Central

    Su, Yanbin; Liu, Yumei; Li, Zhansheng; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Zhang, Yangyong

    2015-01-01

    Head splitting resistance (HSR) in cabbage is an important trait closely related to both quality and yield of head. However, the genetic control of this trait remains unclear. In this study, a doubled haploid (DH) population derived from an intra-cross between head splitting-susceptible inbred cabbage line 79–156 and resistant line 96–100 was obtained and used to analyze inheritance and detect quantitative trait loci (QTLs) for HSR using a mixed major gene/polygene inheritance analysis and QTL mapping. HSR can be attributed to additive-epistatic effects of three major gene pairs combined with those of polygenes. Negative and significant correlations were also detected between head Hsr and head vertical diameter (Hvd), head transverse diameter (Htd) and head weight (Hw). Using the DH population, a genetic map was constructed with simple sequence repeat (SSR) and insertion–deletion (InDel) markers, with a total length of 1065.9 cM and average interval length of 4.4 cM between adjacent markers. Nine QTLs for HSR were located on chromosomes C3, C4, C7, and C9 based on 2 years of phenotypic data using both multiple-QTL mapping and inclusive composite interval mapping. The identified QTLs collectively explained 39.4 to 59.1% of phenotypic variation. Three major QTLs (Hsr 3.2, 4.2, 9.2) showing a relatively larger effect were robustly detected in different years or with different mapping methods. The HSR trait was shown to have complex genetic mechanisms. Results from QTL mapping and classical genetic analysis were consistent. The QTLs obtained in this study should be useful for molecular marker-assisted selection in cabbage breeding and provide a foundation for further research on HSR genetic regulation. PMID:26406606

  17. QTL Analysis of Head Splitting Resistance in Cabbage (Brassica oleracea L. var. capitata) Using SSR and InDel Makers Based on Whole-Genome Re-Sequencing.

    PubMed

    Su, Yanbin; Liu, Yumei; Li, Zhansheng; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Zhang, Yangyong

    2015-01-01

    Head splitting resistance (HSR) in cabbage is an important trait closely related to both quality and yield of head. However, the genetic control of this trait remains unclear. In this study, a doubled haploid (DH) population derived from an intra-cross between head splitting-susceptible inbred cabbage line 79-156 and resistant line 96-100 was obtained and used to analyze inheritance and detect quantitative trait loci (QTLs) for HSR using a mixed major gene/polygene inheritance analysis and QTL mapping. HSR can be attributed to additive-epistatic effects of three major gene pairs combined with those of polygenes. Negative and significant correlations were also detected between head Hsr and head vertical diameter (Hvd), head transverse diameter (Htd) and head weight (Hw). Using the DH population, a genetic map was constructed with simple sequence repeat (SSR) and insertion-deletion (InDel) markers, with a total length of 1065.9 cM and average interval length of 4.4 cM between adjacent markers. Nine QTLs for HSR were located on chromosomes C3, C4, C7, and C9 based on 2 years of phenotypic data using both multiple-QTL mapping and inclusive composite interval mapping. The identified QTLs collectively explained 39.4 to 59.1% of phenotypic variation. Three major QTLs (Hsr 3.2, 4.2, 9.2) showing a relatively larger effect were robustly detected in different years or with different mapping methods. The HSR trait was shown to have complex genetic mechanisms. Results from QTL mapping and classical genetic analysis were consistent. The QTLs obtained in this study should be useful for molecular marker-assisted selection in cabbage breeding and provide a foundation for further research on HSR genetic regulation.

  18. QTL Analysis of Head Splitting Resistance in Cabbage (Brassica oleracea L. var. capitata) Using SSR and InDel Makers Based on Whole-Genome Re-Sequencing.

    PubMed

    Su, Yanbin; Liu, Yumei; Li, Zhansheng; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Zhang, Yangyong

    2015-01-01

    Head splitting resistance (HSR) in cabbage is an important trait closely related to both quality and yield of head. However, the genetic control of this trait remains unclear. In this study, a doubled haploid (DH) population derived from an intra-cross between head splitting-susceptible inbred cabbage line 79-156 and resistant line 96-100 was obtained and used to analyze inheritance and detect quantitative trait loci (QTLs) for HSR using a mixed major gene/polygene inheritance analysis and QTL mapping. HSR can be attributed to additive-epistatic effects of three major gene pairs combined with those of polygenes. Negative and significant correlations were also detected between head Hsr and head vertical diameter (Hvd), head transverse diameter (Htd) and head weight (Hw). Using the DH population, a genetic map was constructed with simple sequence repeat (SSR) and insertion-deletion (InDel) markers, with a total length of 1065.9 cM and average interval length of 4.4 cM between adjacent markers. Nine QTLs for HSR were located on chromosomes C3, C4, C7, and C9 based on 2 years of phenotypic data using both multiple-QTL mapping and inclusive composite interval mapping. The identified QTLs collectively explained 39.4 to 59.1% of phenotypic variation. Three major QTLs (Hsr 3.2, 4.2, 9.2) showing a relatively larger effect were robustly detected in different years or with different mapping methods. The HSR trait was shown to have complex genetic mechanisms. Results from QTL mapping and classical genetic analysis were consistent. The QTLs obtained in this study should be useful for molecular marker-assisted selection in cabbage breeding and provide a foundation for further research on HSR genetic regulation. PMID:26406606

  19. Modified Team-Based Learning Strategy to Improve Human Anatomy Learning: A Pilot Study at the Universidad Del Norte in Barranquilla, Colombia

    ERIC Educational Resources Information Center

    Martínez, Emilio G.; Tuesca, Rafael

    2014-01-01

    As part of an institutional program sponsored by the Centre for Teaching Excellence at the Universidad del Norte, Barranquilla, Colombia, we developed an educational research study on two sessions of human anatomy in which we combined team-based learning (TBL) and the use of iPads. Study data included the TBL, assessments applied during the…

  20. Taxonomic Position and Phylogeny of the Genus Vargasiella (Orchidaceae, Vandoideae) Based on Molecular and Morphological Evidence

    PubMed Central

    Szlachetko, Dariusz L.; Górniak, Marcin; Kolanowska, Marta; Mytnik-Ejsmont, Joanna; Kowalkowska, Agnieszka K.; Rutkowski, Piotr; Koliński, Tomasz

    2014-01-01

    Since the description of the Neotropical genus Vargasiella in 1952, its taxonomic position has remained unclear, mainly due to a lack of sufficient data. In this study, the taxonomic position of Vargasiella was revised based on the outcomes of macro- and micromorphological studies, analyses of selected molecular markers and ecological methods of niche distribution modeling. The phylogenetic relationships were inferred using three DNA markers: matK, trnL-F and ITS sequences. The morphological studies included the analysis of macromorphological features of herbarium specimens as well as micromorphological examination of preserved flowers. The ecological niche modeling was applied to identify the distribution of the suitable niches of the studied taxa. The relationships between Vargasiella and most similar taxa remain unresolved based on the molecular analysis. The outcomes from the morphological studies indicated significant differences between Vargasiella, Warrea and Warreopsis. Moreover, a niche shift in response to changing climate after the last glacial maximum is observed in Vargasiella, while no substantial changes in the occupied habitats were identified in the other related taxa. The clocktree of the Zygopetaleae estimated from the matK gene indicated that the most recent common ancestors of Vargasiella, Warrea and Warreopsis originated in the Miocene, while the divergence time for Vargasiella and Warrea was assessed at approximately 5.4 Ma ago. Vargasiella seems to be an outshoot of the main branch of evolution of the Zygopetaleae. It is noteworthy that the Vargasiella-Warrea dichotomy could have taken place later than the divergence of Warreopsis from the mutual lineage. The molecular analysis and morphological data suggest that Vargasiella and Warrea could have evolved from a common ancestor. Accumulation of morphological differences and acceleration of the evolution of Vargasiella were more intensive than in other Warreinae and this could probably be

  1. Molecular basis for specificity in the druggable kinome: sequence-based analysis

    PubMed Central

    Chen, Jianping; Zhang, Xi

    2007-01-01

    Motivation Rational design of kinase inhibitors remains a challenge partly because there is no clear delineation of the molecular features that direct the pharmacological impact towards clinically relevant targets. Standard factors governing ligand affinity, such as potential for intermolecular hydrophobic interactions or for intermolecular hydrogen bonding do not provide good markers to assess cross reactivity. Thus, a core question in the informatics of drug design is what type of molecular similarity among targets promotes promiscuity and what type of molecular difference governs specificity. This work answers the question for a sizable screened sample of the human pharmacokinome including targets with unreported structure. Results We show that drug design aimed at promoting pairwise interactions between ligand and kinase target actually fosters promiscuity because of the high conservation of the partner groups on or around the ATP-binding site of the kinase. Alternatively, we focus on a structural marker that may be reliably determined from sequence and measures dehydration propensities mostly localized on the loopy regions of kinases. Based on this marker, we construct a sequence-based kinase classifier that enables the accurate prediction of pharmacological differences. Our indicator is a micro-environmental descriptor that quantifies the propensity for water exclusion around preformed polar pairs. The results suggest that targeting polar dehydration patterns heralds a new generation of drugs that enable a tighter control of specificity than designs aimed at promoting ligand–kinase pairwise interactions. Availability The predictor of polar hot spots for dehydration propensity, or solvent-accessible hydrogen bonds in soluble proteins, named YAPView, may be freely downloaded from the University of Chicago website http://protlib.uchicago.edu/dloads.html PMID:17255140

  2. Hybrid Materials Based on Magnetic Layered Double Hydroxides: A Molecular Perspective.

    PubMed

    Abellán, Gonzalo; Martí-Gastaldo, Carlos; Ribera, Antonio; Coronado, Eugenio

    2015-06-16

    Design of functional hybrids lies at the very core of synthetic chemistry as it has enabled the development of an unlimited number of solids displaying unprecedented or even improved properties built upon the association at the molecular level of quite disparate components by chemical design. Multifunctional hybrids are a particularly appealing case among hybrid organic/inorganic materials. Here, chemical knowledge is used to deploy molecular components bearing different functionalities within a single solid so that these properties can coexist or event interact leading to unprecedented phenomena. From a molecular perspective, this can be done either by controlled assembly of organic/inorganic molecular tectons into an extended architecture of hybrid nature or by intercalation of organic moieties within the empty channels or interlamellar space offered by inorganic solids with three-dimensional (MOFs, zeolites, and mesoporous hosts) or layered structures (phosphates, silicates, metal dichalcogenides, or anionic clays). This Account specifically illustrates the use of layered double hydroxides (LDHs) in the preparation of magnetic hybrids, in line with the development of soft inorganic chemistry processes (also called "Chimie Douce"), which has significantly contributed to boost the preparation hybrid materials based on solid-state hosts and subsequent development of applications. Several features sustain the importance of LDHs in this context. Their magnetism can be manipulated at a molecular level by adequate choice of constituting metals and interlayer separation for tuning the nature and extent of magnetic interactions across and between planes. They display unparalleled versatility in accommodating a broad range of anionic species in their interlamellar space that encompasses not only simple anions but chemical systems of increasing dimensionality and functionalities. Their swelling characteristics allow for their exfoliation in organic solvents with high

  3. Rock cliffs hazard analysis based on remote geostructural surveys: The Campione del Garda case study (Lake Garda, Northern Italy)

    NASA Astrophysics Data System (ADS)

    Ferrero, A. M.; Migliazza, M.; Roncella, R.; Segalini, A.

    2011-02-01

    The town of Campione del Garda (located on the west coast of Lake Garda) and its access road have been historically subject to rockfall phenomena with risk for public security in several areas of the coast. This paper presents a study devoted to the determination of risk for coastal cliffs and the design of mitigation measures. Our study was based on statistical rockfall analysis performed with a commercial code and on stability analysis of rock slopes based on the key block method. Hazard from block kinematics and rock-slope failure are coupled by applying the Rockfall Hazard Assessment Procedure (RHAP). Because of the huge dimensions of the slope, its morphology and the geostructural survey were particularly complicated and demanding. For these reasons, noncontact measurement methods, based on aerial photogrammetry by helicopter, were adopted. A special software program, developed by the authors, was applied for discontinuity identification and for their orientation measurements. The potentially of aerial photogrammetic survey in rock mechanic application and its improvement in the rock mass knowledge is analysed in the article.

  4. Molecular Subtyping of Serous Ovarian Cancer Based on Multi-omics Data

    PubMed Central

    Zhang, Zhe; Huang, Ke; Gu, Chenglei; Zhao, Luyang; Wang, Nan; Wang, Xiaolei; Zhao, Dongsheng; Zhang, Chenggang; Lu, Yiming; Meng, Yuanguang

    2016-01-01

    Classification of ovarian cancer by morphologic features has a limited effect on serous ovarian cancer (SOC) treatment and prognosis. Here, we proposed a new system for SOC subtyping based on the molecular categories from the Cancer Genome Atlas project. We analyzed the DNA methylation, protein, microRNA, and gene expression of 1203 samples from 599 serous ovarian cancer patients. These samples were divided into nine subtypes based on RNA-seq data, and each subtype was found to be associated with the activation and/or suppression of the following four biological processes: immunoactivity, hormone metabolic, mesenchymal development and the MAPK signaling pathway. We also identified four DNA methylation, two protein expression, six microRNA sequencing and four pathway subtypes. By integrating the subtyping results across different omics platforms, we found that most RNA-seq subtypes overlapped with one or two subtypes from other omics data. Our study sheds light on the molecular mechanisms of SOC and provides a new perspective for the more accurate stratification of its subtypes. PMID:27184229

  5. Molecular Imaging of Tumor Hypoxia: Existing Problems and Their Potential Model-Based Solutions.

    PubMed

    Shi, Kuangyu; Ziegler, Sibylle I; Vaupel, Peter

    2016-01-01

    Molecular imaging of tissue hypoxia generates contrast in hypoxic areas by applying hypoxia-specific tracers in organisms. In cancer tissue, the injected tracer needs to be transported over relatively long distances and accumulates slowly in hypoxic regions. Thus, the signal-to-background ratio of hypoxia imaging is very small and a non-specific accumulation may suppress the real hypoxia-specific signals. In addition, the heterogeneous tumor microenvironment makes the assessment of the tissue oxygenation status more challenging. In this study, the diffusion potential of oxygen and of a hypoxia tracer for 4 different hypoxia subtypes: ischemic acute hypoxia, hypoxemic acute hypoxia, diffusion-limited chronic hypoxia and anemic chronic hypoxia are theoretically assessed. In particular, a reaction-diffusion equation is introduced to quantitatively analyze the interstitial diffusion of the hypoxia tracer [(18)F]FMISO. Imaging analysis strategies are explored based on reaction-diffusion simulations. For hypoxia imaging of low signal-to-background ratio, pharmacokinetic modelling has advantages to extract underlying specific binding signals from non-specific background signals and to improve the assessment of tumor oxygenation. Different pharmacokinetic models are evaluated for the analysis of the hypoxia tracer [(18)F]FMISO and optimal analysis model were identified accordingly. The improvements by model-based methods for the estimation of tumor oxygenation are in agreement with experimental data. The computational modelling offers a tool to explore molecular imaging of hypoxia and pharmacokinetic modelling is encouraged to be employed in the corresponding data analysis. PMID:27526129

  6. Network analysis of genes regulated in renal diseases: implications for a molecular-based classification

    PubMed Central

    Bhavnani, Suresh K; Eichinger, Felix; Martini, Sebastian; Saxman, Paul; Jagadish, HV; Kretzler, Matthias

    2009-01-01

    Background Chronic renal diseases are currently classified based on morphological similarities such as whether they produce predominantly inflammatory or non-inflammatory responses. However, such classifications do not reliably predict the course of the disease and its response to therapy. In contrast, recent studies in diseases such as breast cancer suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. This article describes how we extracted gene expression profiles from biopsies of patients with chronic renal diseases, and used network visualizations and associated quantitative measures to rapidly analyze similarities and differences between the diseases. Results The analysis revealed three main regularities: (1) Many genes associated with a single disease, and fewer genes associated with many diseases. (2) Unexpected combinations of renal diseases that share relatively large numbers of genes. (3) Uniform concordance in the regulation of all genes in the network. Conclusion The overall results suggest the need to define a molecular-based classification of renal diseases, in addition to hypotheses for the unexpected patterns of shared genes and the uniformity in gene concordance. Furthermore, the results demonstrate the utility of network analyses to rapidly understand complex relationships between diseases and regulated genes. PMID:19761573

  7. Unified molecular picture of the surfaces of aqueous acid, base, and salt solutions.

    PubMed

    Mucha, Martin; Frigato, Tomaso; Levering, Lori M; Allen, Heather C; Tobias, Douglas J; Dang, Liem X; Jungwirth, Pavel

    2005-04-28

    The molecular structure of the interfacial regions of aqueous electrolytes is poorly understood, despite its crucial importance in many biological, technological, and atmospheric processes. A long-term controversy pertains between the standard picture of an ion-free surface layer and the strongly ion specific behavior indicating in many cases significant propensities of simple inorganic ions for the interface. Here, we present a unified and consistent view of the structure of the air/solution interface of aqueous electrolytes containing monovalent inorganic ions. Molecular dynamics calculations show that in salt solutions and bases the positively charged ions, such as alkali cations, are repelled from the interface, whereas the anions, such as halides or hydroxide, exhibit a varying surface propensity, correlated primarily with the ion polarizability and size. The behavior of acids is different due to a significant propensity of hydronium cations for the air/solution interface. Therefore, both cations and anions exhibit enhanced concentrations at the surface and, consequently, these acids (unlike bases and salts) reduce the surface tension of water. The results of the simulations are supported by surface selective nonlinear vibrational spectroscopy, which reveals among other things that the hydronium cations are present at the air/solution interface. The ion specific propensities for the air/solution interface have important implications for a whole range of heterogeneous physical and chemical processes, including atmospheric chemistry of aerosols, corrosion processes, and bubble coalescence.

  8. On the optimal design of molecular sensing interfaces with lipid bilayer assemblies - A knowledge based approach

    NASA Astrophysics Data System (ADS)

    Siontorou, Christina G.

    2012-12-01

    Biosensors are analytic devices that incorporate a biochemical recognition system (biological, biologicalderived or biomimic: enzyme, antibody, DNA, receptor, etc.) in close contact with a physicochemical transducer (electrochemical, optical, piezoelectric, conductimetric, etc.) that converts the biochemical information, produced by the specific biological recognition reaction (analyte-biomolecule binding), into a chemical or physical output signal, related to the concentration of the analyte in the measuring sample. The biosensing concept is based on natural chemoreception mechanisms, which are feasible over/within/by means of a biological membrane, i.e., a structured lipid bilayer, incorporating or attached to proteinaceous moieties that regulate molecular recognition events which trigger ion flux changes (facilitated or passive) through the bilayer. The creation of functional structures that are similar to natural signal transduction systems, correlating and interrelating compatibly and successfully the physicochemical transducer with the lipid film that is self-assembled on its surface while embedding the reconstituted biological recognition system, and at the same time manage to satisfy the basic conditions for measuring device development (simplicity, easy handling, ease of fabrication) is far from trivial. The aim of the present work is to present a methodological framework for designing such molecular sensing interfaces, functioning within a knowledge-based system built on an ontological platform for supplying sub-systems options, compatibilities, and optimization parameters.

  9. Targeted Isolation of Indolopyridoquinazoline Alkaloids from Conchocarpus fontanesianus Based on Molecular Networks.

    PubMed

    Cabral, Rodrigo Sant'Ana; Allard, Pierre-Marie; Marcourt, Laurence; Young, Maria Cláudia Marx; Queiroz, Emerson Ferreira; Wolfender, Jean-Luc

    2016-09-23

    A dichloromethane-soluble fraction of the stem bark of Conchocarpus fontanesianus showed antifungal activity against Candida albicans in a bioautography assay. Off-line high-pressure liquid chromatography activity-based profiling of this extract enabled a precise localization of the compounds responsible for the antifungal activity that were isolated and identified as the known compounds flindersine (17) and 8-methoxyflindersine (18). As well as the identification of the bioactive principles, the ultra-high-pressure liquid chromatography-high-resolution mass spectrometry metabolite profiling of the dichloromethane stem bark fraction allowed the detection of more than 1000 components. Some of these could be assigned putatively to secondary metabolites previously isolated from the family Rutaceae. Generation of a molecular network based on MS(2) spectra indicated the presence of indolopyridoquinazoline alkaloids and related scaffolds. Efficient targeted isolation of these compounds was performed by geometric transfer of the analytical high-pressure liquid chromatography profiling conditions to preparative medium-pressure liquid chromatography. This yielded six new indolopyridoquinazoline alkaloids (5, 16, 19-22) that were assigned structurally. The medium-pressure liquid chromatography separations afforded additionally 16 other compounds. This work has demonstrated the usefulness of molecular networks to target the isolation of new natural products and the value of this approach for dereplication. A detailed analysis of the constituents of the stem bark of C. fontanesianus was conducted. PMID:27557347

  10. Electrochemical sensor for dopamine based on a novel graphene-molecular imprinted polymers composite recognition element.

    PubMed

    Mao, Yan; Bao, Yu; Gan, Shiyu; Li, Fenghua; Niu, Li

    2011-10-15

    A novel composite of graphene sheets/Congo red-molecular imprinted polymers (GSCR-MIPs) was synthesized through free radical polymerization (FRP) and applied as a molecular recognition element to construct dopamine (DA) electrochemical sensor. The template molecules (DA) were firstly absorbed at the GSCR surface due to their excellent affinity, and subsequently, selective copolymerization of methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) was further achieved at the GSCR surface. Potential scanning was presented to extract DA molecules from the imprinted polymers film, and as a result, DA could be rapidly and completely removed by this way. With regard to the traditional MIPs, the GSCR-MIPs not only possessed a faster desorption and adsorption dynamics, but also exhibited a higher selectivity and binding capacity toward DA molecule. As a consequence, an electrochemical sensor for highly sensitive and selective detection of DA was successfully constructed as demonstration based on the synthesized GSCR-MIPs nanocomposites. Under experimental conditions, selective detection of DA in a linear concentration range of 1.0 × 10(-7)-8.3 × 10(-4)M was obtained, which revealed a lower limit of detection and wider linear response compared to some previously reported DA electrochemical MIPs sensors. The new DA electrochemical sensor based on GSCR-MIPs composites also exhibited excellent repeatability, which expressed as relative standard deviation (RSD) was about 2.50% for 30 repeated analyses of 20 μM DA. PMID:21824760

  11. A molecular-beacon-based screen for small molecule inhibitors of miRNA maturation.

    PubMed

    Bose, Debojit; Jayaraj, Gopal Gunanathan; Kumar, Santosh; Maiti, Souvik

    2013-05-17

    miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have described the deregulation of numerous miRNA to be causally associated with many diseases, including cancer. These studies have highlighted the potential for development of therapeutic modalities against miRNA. Previous screening protocols, for small molecules targeting miRNA function, are either costly or technically too complex to be applied in a high-throughput manner in standard chemical laboratories. We describe a simple in vitro screening method using a DNA-based molecular beacon that overcomes the limitations associated with earlier screens. We used this method to identify inhibitors of miR-27a function from a library of 14 aminoglycosides as a pilot study. Inhibitory molecules identified were further scrutinized to identify the validity of screen. With this proof of concept we illustrate the utility of a scalable molecular-beacon-based screening strategy for miRNA inhibitors.

  12. Polydimethysiloxane Modified Silica Nanochannel Membrane for Hydrophobicity-Based Molecular Filtration and Detection.

    PubMed

    Lin, Xingyu; Zhang, Bowen; Yang, Qian; Yan, Fei; Hua, Xin; Su, Bin

    2016-08-01

    We report in this work the fabrication of ultrathin silica nanochannel membranes inhomogeneously modified by polydimethysiloxane (PDMS), designated as PDMS-SNM, for hydrophobicity-based molecular filtration and detection. The modification was accomplished by spatially selective evaporation of hydrophobic PDMS oligomers onto the top surface of the membrane and orifice of silica nanochannels. Thanks to this hydrophobic ultrathin layer and beneath ultrasmall channels (2-3 nm in diameter), only small hydrophobic molecules are able to transport through the PDMS-SNM, whereas hydrophilic and large ones are remarkably inhibited. We first employed this PDMS-SNM as the molecular sieving matrix for selective electrochemical detection of hydrophobic organophosphates (OPs) in milk samples without pretreatment. The PDMS-SNM modified electrode displayed an excellent analytical performance and antifouling/anti-interference ability. We also prepared the free-standing PDMS-SNM consisting of perforated channels, which could filtrate molecules based on their hydrophobicity with an excellent selectivity. As demonstrated, 2,4,6-trinitrotoluene and dopamine could be separated with a selectivity coefficient as high as 335. Moreover, because of the inhomogeneous nanochannel structure and ultrasmall thickness, a remarkably high flux of hydrophobic molecules across the PDMS-SNM was obtained, which was 3-4 orders of magnitude higher than that reported previously. PMID:27414252

  13. A molecular ruler based on plasmon coupling of single gold andsilver nanoparticles

    SciTech Connect

    Sonnichsen, Carsten; Reinhard, Bjorn M.; Liphardt, Jan; Alivisatos, A. Paul

    2005-05-22

    Molecular rulers based on Foerster Resonance Energy Transfer (FRET) that report conformational changes and intramolecular distances of single biomolecules have helped to understand important biological processes. However, these rulers suffer from low and fluctuating signal intensities from single dyes and limited observation time due to photobleaching. The plasmon resonance in noble metal particles has been suggested as an alternative probe to overcome the limitations of organic fluorophores and the coupling of plasmons in nearby particles has been exploited to detect particle aggregation by a distinct color change in bulk experiments. Here we demonstrate that plasmon coupling can be used to monitor distances between single pairs of gold and silver nanoparticles. We use this effect to follow the directed assembly of gold and silver nanoparticle dimers in real time and to study the time dynamics of single DNA hybridization events. These ''plasmon rulers'' allowed us to continuously monitor separations of up to 70 nm for more than 3000 seconds. Single molecule in vitro studies of biological processes previously inaccessible with fluorescence based molecular rulers are enabled with plasmon rulers with extended time and distance range.

  14. Molecular cancer classification using a meta-sample-based regularized robust coding method

    PubMed Central

    2014-01-01

    Motivation Previous studies have demonstrated that machine learning based molecular cancer classification using gene expression profiling (GEP) data is promising for the clinic diagnosis and treatment of cancer. Novel classification methods with high efficiency and prediction accuracy are still needed to deal with high dimensionality and small sample size of typical GEP data. Recently the sparse representation (SR) method has been successfully applied to the cancer classification. Nevertheless, its efficiency needs to be improved when analyzing large-scale GEP data. Results In this paper we present the meta-sample-based regularized robust coding classification (MRRCC), a novel effective cancer classification technique that combines the idea of meta-sample-based cluster method with regularized robust coding (RRC) method. It assumes that the coding residual and the coding coefficient are respectively independent and identically distributed. Similar to meta-sample-based SR classification (MSRC), MRRCC extracts a set of meta-samples from the training samples, and then encodes a testing sample as the sparse linear combination of these meta-samples. The representation fidelity is measured by the l2-norm or l1-norm of the coding residual. Conclusions Extensive experiments on publicly available GEP datasets demonstrate that the proposed method is more efficient while its prediction accuracy is equivalent to existing MSRC-based methods and better than other state-of-the-art dimension reduction based methods. PMID:25473795

  15. Kazusa Marker DataBase: a database for genomics, genetics, and molecular breeding in plants.

    PubMed

    Shirasawa, Kenta; Isobe, Sachiko; Tabata, Satoshi; Hirakawa, Hideki

    2014-09-01

    In order to provide useful genomic information for agronomical plants, we have established a database, the Kazusa Marker DataBase (http://marker.kazusa.or.jp). This database includes information on DNA markers, e.g., SSR and SNP markers, genetic linkage maps, and physical maps, that were developed at the Kazusa DNA Research Institute. Keyword searches for the markers, sequence data used for marker development, and experimental conditions are also available through this database. Currently, 10 plant species have been targeted: tomato (Solanum lycopersicum), pepper (Capsicum annuum), strawberry (Fragaria × ananassa), radish (Raphanus sativus), Lotus japonicus, soybean (Glycine max), peanut (Arachis hypogaea), red clover (Trifolium pratense), white clover (Trifolium repens), and eucalyptus (Eucalyptus camaldulensis). In addition, the number of plant species registered in this database will be increased as our research progresses. The Kazusa Marker DataBase will be a useful tool for both basic and applied sciences, such as genomics, genetics, and molecular breeding in crops. PMID:25320561

  16. Remote Stabilization of Copper Paddlewheel Based Molecular Building Blocks in Metal-Organic Frameworks

    SciTech Connect

    Gao, Wen-Yang; Cai, Rong; Pham, Tony; Forrest, Katherine A.; Hogan, Adam; Nugent, Patrick; Williams, Kia; Wojtas, Lukasz; Luebke, Ryan; Weseliinski, Lukasz J.; Zaworotko, Michael J.; Space, Brian; Chen, Yu-Sheng; Eddaoudi, Mohamed; Shi, Xiaodong; Ma, Shengqian

    2015-08-21

    Copper paddlewheel based molecular building blocks (MBBs) are ubiquitous and have been widely employed for the construction of highly porous metal–organic frameworks (MOFs). However, most copper paddlewheel based MOFs fail to retain their structural integrity in the presence of water. This instability is directly correlated to the plausible displacement of coordinating carboxylates in the copper paddlewheel MBB, [Cu₂(O₂C-)₄], by the strongly coordinating water molecules. In this comprehensive study, we illustrate the chemical stability control in the rht-MOF platform via strengthening the coordinating bonds within the triangular inorganic MBB, [Cu₃O(N4–x(CH)xC-)₃] (x = 0, 1, or 2). Remotely, the chemical stabilization propagated into the paddlewheel MBB to afford isoreticular rht-MOFs with remarkably enhanced water/chemical stabilities compared to the prototypal rht-MOF-1.

  17. Kazusa Marker DataBase: a database for genomics, genetics, and molecular breeding in plants.

    PubMed

    Shirasawa, Kenta; Isobe, Sachiko; Tabata, Satoshi; Hirakawa, Hideki

    2014-09-01

    In order to provide useful genomic information for agronomical plants, we have established a database, the Kazusa Marker DataBase (http://marker.kazusa.or.jp). This database includes information on DNA markers, e.g., SSR and SNP markers, genetic linkage maps, and physical maps, that were developed at the Kazusa DNA Research Institute. Keyword searches for the markers, sequence data used for marker development, and experimental conditions are also available through this database. Currently, 10 plant species have been targeted: tomato (Solanum lycopersicum), pepper (Capsicum annuum), strawberry (Fragaria × ananassa), radish (Raphanus sativus), Lotus japonicus, soybean (Glycine max), peanut (Arachis hypogaea), red clover (Trifolium pratense), white clover (Trifolium repens), and eucalyptus (Eucalyptus camaldulensis). In addition, the number of plant species registered in this database will be increased as our research progresses. The Kazusa Marker DataBase will be a useful tool for both basic and applied sciences, such as genomics, genetics, and molecular breeding in crops.

  18. Functionality in Electrospun Nanofibrous Membranes Based on Fiber's Size, Surface Area, and Molecular Orientation

    PubMed Central

    Matsumoto, Hidetoshi; Tanioka, Akihiko

    2011-01-01

    Electrospinning is a versatile method for forming continuous thin fibers based on an electrohydrodynamic process. This method has the following advantages: (i) the ability to produce thin fibers with diameters in the micrometer and nanometer ranges; (ii) one-step forming of the two- or three-dimensional nanofiber network assemblies (nanofibrous membranes); and (iii) applicability for a broad spectrum of molecules, such as synthetic and biological polymers and polymerless sol-gel systems. Electrospun nanofibrous membranes have received significant attention in terms of their practical applications. The major advantages of nanofibers or nanofibrous membranes are the functionalities based on their nanoscaled-size, highly specific surface area, and highly molecular orientation. These functionalities of the nanofibrous membranes can be controlled by their fiber diameter, surface chemistry and topology, and internal structure of the nanofibers. This report focuses on our studies and describes fundamental aspects and applications of electrospun nanofibrous membranes. PMID:24957735

  19. Kazusa Marker DataBase: a database for genomics, genetics, and molecular breeding in plants

    PubMed Central

    Shirasawa, Kenta; Isobe, Sachiko; Tabata, Satoshi; Hirakawa, Hideki

    2014-01-01

    In order to provide useful genomic information for agronomical plants, we have established a database, the Kazusa Marker DataBase (http://marker.kazusa.or.jp). This database includes information on DNA markers, e.g., SSR and SNP markers, genetic linkage maps, and physical maps, that were developed at the Kazusa DNA Research Institute. Keyword searches for the markers, sequence data used for marker development, and experimental conditions are also available through this database. Currently, 10 plant species have been targeted: tomato (Solanum lycopersicum), pepper (Capsicum annuum), strawberry (Fragaria × ananassa), radish (Raphanus sativus), Lotus japonicus, soybean (Glycine max), peanut (Arachis hypogaea), red clover (Trifolium pratense), white clover (Trifolium repens), and eucalyptus (Eucalyptus camaldulensis). In addition, the number of plant species registered in this database will be increased as our research progresses. The Kazusa Marker DataBase will be a useful tool for both basic and applied sciences, such as genomics, genetics, and molecular breeding in crops. PMID:25320561

  20. Cucurbiturils: molecular nanocapsules for time-resolved fluorescence-based assays.

    PubMed

    Marquez, Cesar; Huang, Fang; Nau, Werner M

    2004-03-01

    A new fluorescent host-guest system based on the inclusion of the fluorophore 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) into the cavity of the molecular container compound cucurbit[7]uril (CB7) has been designed which possesses an exceedingly long-lived emission (690 ns in aerated water). The large binding constant of (4 +/- 1) x 10(5) M(-1) along with the resistance of the CB7.DBO complex toward external fluorescence quenchers allow the use of CB7 as an enhancer in time-resolved fluorescence-based assays, e.g., to screen enzyme activity or inhibition by using DBO-labeled peptides as substrates. The response of CB7.DBO to different environmental conditions and possible quenchers are described.

  1. Innovative molecular-based fluorescent nanoparticles for multicolor single particle tracking in cells

    NASA Astrophysics Data System (ADS)

    Daniel, Jonathan; Godin, Antoine G.; Palayret, Matthieu; Lounis, Brahim; Cognet, Laurent; Blanchard-Desce, Mireille

    2016-03-01

    Based on an original molecular-based design, we present bright and photostable fluorescent organic nanoparticles (FONs) showing excellent colloidal stability in various aqueous environments. Complementary near-infrared emitting and green emitting FONs were prepared using a simple, fast and robust protocol. Both types of FONs could be simultaneously imaged at the single-particle level in solution as well as in biological environments using a monochromatic excitation and a dual-color fluorescence microscope. No evidence of acute cytotoxicity was found upon incubation of live cells with mixed solutions of FONs, and both types of nanoparticles were found internalized in the cells where their motion could be simultaneously tracked at video-rate up to minutes. These fluorescent organic nanoparticles open a novel non-toxic alternative to existing nanoparticles for imaging biological structures, compatible with live-cell experiments and specially fitted for multicolor single particle tracking.

  2. Facile nucleation of gold nanoparticles on graphene-based thin films from Au144 molecular precursors

    NASA Astrophysics Data System (ADS)

    Venter, Andrei; Hesari, Mahdi; Shafiq Ahmed, M.; Bauld, Reg; Workentin, Mark S.; Fanchini, Giovanni

    2014-04-01

    We demonstrate a facile and cost effective method to obtain gold nanoparticles on graphene by dispersing Au144 molecular nanoclusters by spin coating them in thin layers on graphene-based films and subsequent annealing in a controlled atmosphere. The graphene-based thin films used for these experiments are prepared by solvent-assisted exfoliation of graphite in water in the presence of ribonucleic acid as a surfactant and by subsequent vacuum filtration of the resulting graphene-containing suspensions. Not only is this method easily reproducible, but it leads to gold nanoparticles that are not dependent in size on the number of graphene layers beneath them. This is a distinct advantage over other methods. Plasmonic effects have been detected in our gold nanoparticle-decorated graphene layers, indicating that these thin films may be useful in applications such as plasmonic solar cells and optical memory devices.

  3. A molecular approach to the Kondo problem in Carbon based systems

    NASA Astrophysics Data System (ADS)

    Soriano, Maria; Jacob, David; Palacios, Juan Jose

    2014-03-01

    There has been a great effort in recent years to understand the emerging Kondo-like resonances in different magnetic molecules such as MnPc. Theoretical approaches based on atomic models have proven to be very useful for the study of this phenomenon when the magnetic moment is essentially localized on a magnetic atom. Nevertheless the Kondo effect can arise in pure carbon-based systems as has been demonstrated experimentally in fullerenes and carbon nanotubes. In this communication we present a multiorbital Anderson model where the orbitals are not atomic but molecular orbitals. This model is fully obtained from Density Functional Theory calculation in combination with Green's functions methodologies. Standard impurity solver techniques are used to solve the model which is applied to fullerenes and other nanographene structures.

  4. Labyrinthine water flow across multilayer graphene-based membranes: Molecular dynamics versus continuum predictions.

    PubMed

    Yoshida, Hiroaki; Bocquet, Lydéric

    2016-06-21

    In this paper, we investigate the hydrodynamic permeance of water through graphene-based membranes, inspired by recent experimental findings on graphene-oxide membranes. We consider the flow across multiple graphene layers having nanoslits in a staggered alignment, with an inter-layer distance ranging from sub-nanometer to a few nanometers. We compare results for the permeability obtained by means of molecular dynamics simulations to continuum predictions obtained by using the lattice Boltzmann calculations and hydrodynamic modelization. This highlights that, in spite of extreme confinement, the permeability across the graphene-based membrane is quantitatively predicted on the basis of a continuum expression, taking properly into account entrance and slippage effects of the confined water flow. Our predictions refute the breakdown of hydrodynamics at small scales in these membrane systems. They constitute a benchmark to which we compare published experimental data. PMID:27334184

  5. Molecular beacon-based enzyme-free strategy for amplified DNA detection.

    PubMed

    Huang, Jiahao; Wu, Jueqi; Li, Zhigang

    2016-05-15

    We report an enzyme-free, sensitive strategy for DNA detections through fluorescence amplification. The sensing method employs molecular beacons (MBs) and two single-stranded helper DNA probes. In the presence of a DNA target, it binds and opens an MB. This triggers the hybridizations between the MB and helper probes, and consequently releases the DNA target, which becomes available to react with another MB and enhances the fluorescence emission of the MBs. The detection limit of the proposed strategy is 0.58 pM, which is about 3 orders of magnitude better than the conventional MB-based method. This method is also fast and exhibits good selectivity. It is superior to previous MB-based amplification approaches employing enzymes or nanomaterials.

  6. Novel siRNA-based molecular beacons for dual imaging and therapy.

    PubMed

    Chang, Emmanuel; Zhu, Ming-Qiang; Drezek, Rebekah

    2007-04-01

    Short interfering RNAs (siRNAs) have become a mainstream tool reliably used to study and silence protein expression. We offer a proof-of-principle demonstration that siRNAs may be modified into a siRNA-based molecular beacon that activates upon binding to sequence-specific mRNA in cells while mediating RNA interference. We successfully demonstrate detection and knockdown of telomerase expression in human breast cancer cells. This probe provides a novel look at siRNA target validation that is not currently possible in live cells and holds promising potential in biological applications for disease detection and therapy based on mRNA expression, such as a telomerase-targeted siRNA probe in cancer.

  7. Development of molecular resists based on Phenyl[4]calixarene for EBL

    NASA Astrophysics Data System (ADS)

    Takasuka, Masaaki; Okada, Yu; Hayashi, Hiromi; Echigo, Masatoshi

    2011-04-01

    In this paper, we report current performance of the negative-tone molecular resists based on calix[4]resorcinarene (CRA) by Electron Beam Lithography (EBL). We have developed hydroxyphenyl calix[4]resorcinarenes (H-CRAs) designed hydroxy-groups outer to adhere patterns to wafers. Hydroxy groups help patterns adhere to wafers, to restrain collapse of patterns. Moreover, we additionally controlled hydrophobicity of H-CRA by the alkyl-groups (R), which make the sensitivity higher. The negative-tone resist based on these H-CRAs shows well-defined 25-50nm half-pitch patterns, and the increase in hydrophobicity of H-CRA by the alkyl-groups (R) made the high sensitivity. Furthermore, the optimization of these resist formulation improved sensitivity and LER.

  8. Molecular beacon-based enzyme-free strategy for amplified DNA detection.

    PubMed

    Huang, Jiahao; Wu, Jueqi; Li, Zhigang

    2016-05-15

    We report an enzyme-free, sensitive strategy for DNA detections through fluorescence amplification. The sensing method employs molecular beacons (MBs) and two single-stranded helper DNA probes. In the presence of a DNA target, it binds and opens an MB. This triggers the hybridizations between the MB and helper probes, and consequently releases the DNA target, which becomes available to react with another MB and enhances the fluorescence emission of the MBs. The detection limit of the proposed strategy is 0.58 pM, which is about 3 orders of magnitude better than the conventional MB-based method. This method is also fast and exhibits good selectivity. It is superior to previous MB-based amplification approaches employing enzymes or nanomaterials. PMID:26774091

  9. Molecular docking, molecular dynamics simulation, and structure-based 3D-QSAR studies on estrogenic activity of hydroxylated polychlorinated biphenyls.

    PubMed

    Li, Xiaolin; Ye, Li; Wang, Xiaoxiang; Wang, Xinzhou; Liu, Hongling; Qian, Xiangping; Zhu, Yongliang; Yu, Hongxia

    2012-12-15

    Hydroxylated polychlorinated biphenyls (HO-PCBs), major metabolites of PCBs, have been reported to present agonist or antagonist interactions with estrogen receptor α (ERα) and induce ER-mediated responses. In this work, a multistep framework combining molecular docking, molecular dynamics (MD) simulations, and structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed to explore the influence of structural features on the estrogenic activities of HO-PCBs, and to investigate the molecular mechanism of ERα-ligand interactions. The CoMSIA (comparative molecular similarity indices analysis) model was developed from the conformations obtained from molecular docking. The model exhibited statistically significant results as the cross-validated correlation coefficient q² was 0.648, the non-cross-validated correlation coefficient r² was 0.968, and the external predictive correlation coefficient r(pred)² was 0.625. The key amino acid residues were identified by molecular docking, and the detailed binding modes of the compounds with different activities were determined by MD simulations. The binding free energies correlated well with the experimental activity. An energetic analysis, MM-GBSA energy decomposition, revealed that the van der Waals interaction was the major driving force for the binding of compounds to ERα. The hydrogen bond interactions between the ligands and residue His524 help to stabilize the conformation of ligands at the binding pocket. These results are expected to be beneficial to predict estrogenic activities of other HO-PCB congeners and helpful for understanding the binding mechanism of HO-PCBs and ERα. PMID:23137989

  10. Interpretation of pH-activity profiles for acid-base catalysis from molecular simulations.

    PubMed

    Dissanayake, Thakshila; Swails, Jason M; Harris, Michael E; Roitberg, Adrian E; York, Darrin M

    2015-02-17

    The measurement of reaction rate as a function of pH provides essential information about mechanism. These rates are sensitive to the pK(a) values of amino acids directly involved in catalysis that are often shifted by the enzyme active site environment. Experimentally observed pH-rate profiles are usually interpreted using simple kinetic models that allow estimation of "apparent pK(a)" values of presumed general acid and base catalysts. One of the underlying assumptions in these models is that the protonation states are uncorrelated. In this work, we introduce the use of constant pH molecular dynamics simulations in explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a tool to aid in the interpretation of pH-activity data of enzymes and to test the validity of different kinetic models. We apply the methods to RNase A, a prototype acid-base catalyst, to predict the macroscopic and microscopic pK(a) values, as well as the shape of the pH-rate profile. Results for apo and cCMP-bound RNase A agree well with available experimental data and suggest that deprotonation of the general acid and protonation of the general base are not strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling, however, is predicted for the Lys41 and His119 protonation states in apo RNase A, leading to the requirement for a microscopic kinetic model. This type of analysis may be important for other catalytic systems where the active forms of the implicated general acid and base are oppositely charged and more highly correlated. These results suggest a new way for CpHMD/pH-REMD simulations to bridge the gap with experiments to provide a molecular-level interpretation of pH-activity data in studies of enzyme mechanisms.

  11. Multiplexed DNA detection with a composite molecular beacon based on guanine-quenching.

    PubMed

    Xiang, Dong-Shan; Zhai, Kun; Wang, Lian-Zhi

    2013-09-21

    We developed a multiplexed DNA detection method with a composite molecular beacon (MB) probe based on guanine-quenching by synchronous fluorescence analysis. It is demonstrated by two types of tumor-suppressor genes namely exon segments of p16 (T1) and p53 (T2) genes. The composite MB probe includes two loops and two stems, and two fluorophores of 6-carboxyfluorescein group (FAM) and tetramethyl-6-carboxyrhodamine (TAMRA) are connected to the two ends of molecular beacon. Every stem portion of MB include four continuous nucleotides with guanine (G) base as quencher, every loop portion is a probe sequence that is complementary to a corresponding target sequence. In the absence of target DNA, the composite MBs are in the stem-closed form, the fluorescence of FAM and TAMRA are quenched by G bases. At this time, the fluorescence signals of FAM and TAMRA are all very low. In the presence of target DNA, the MBs hybridize with the target DNA and form double-strands, FAM and TAMRA are separated from G bases, and the fluorescence of FAM and TAMRA recovers simultaneously. Thus, the simultaneous detection of two targets of DNA can be realized by measuring fluorescence signals of FAM and TAMRA, respectively. Under the optimum conditions, the fluorescence intensities of FAM and TAMRA all exhibit good linear dependence on their target DNA concentration in the range from 5 × 10(-11) to 5.5 × 10(-9) M. The detection limit of T1 is 4 × 10(-11) M (3σ), and that of T2 is 3 × 10(-11) M. This composite MB can be applied to detect the real sample, and can be applied to detect two aleatoric sequences of DNA. Compared with previously reported methods of detecting multiplexed target DNA with MBs, the proposed method has some advantages including easy synthesis of composite MB probes, low detection cost and shorter analytical time.

  12. Molecular and cell-based therapies for muscle degenerations: a road under construction.

    PubMed

    Berardi, Emanuele; Annibali, Daniela; Cassano, Marco; Crippa, Stefania; Sampaolesi, Maurilio

    2014-01-01

    Despite the advances achieved in understanding the molecular biology of muscle cells in the past decades, there is still need for effective treatments of muscular degeneration caused by muscular dystrophies and for counteracting the muscle wasting caused by cachexia or sarcopenia. The corticosteroid medications currently in use for dystrophic patients merely help to control the inflammatory state and only slightly delay the progression of the disease. Unfortunately, walkers and wheel chairs are the only options for such patients to maintain independence and walking capabilities until the respiratory muscles become weak and the mechanical ventilation is needed. On the other hand, myostatin inhibition, IL-6 antagonism and synthetic ghrelin administration are examples of promising treatments in cachexia animal models. In both dystrophies and cachectic syndrome the muscular degeneration is extremely relevant and the translational therapeutic attempts to find a possible cure are well defined. In particular, molecular-based therapies are common options to be explored in order to exploit beneficial treatments for cachexia, while gene/cell therapies are mostly used in the attempt to induce a substantial improvement of the dystrophic muscular phenotype. This review focuses on the description of the use of molecular administrations and gene/stem cell therapy to treat muscular degenerations. It reviews previous trials using cell delivery protocols in mice and patients starting with the use of donor myoblasts, outlining the likely causes for their poor results and briefly focusing on satellite cell studies that raise new hope. Then it proceeds to describe recently identified stem/progenitor cells, including pluripotent stem cells and in relationship to their ability to home within a dystrophic muscle and to differentiate into skeletal muscle cells. Different known features of various stem cells are compared in this perspective, and the few available examples of their use in

  13. Molecular thermodynamic modeling of ionic liquids using the perturbation-based linear Yukawa isotherm regularity.

    PubMed

    Sohrabi Mahboub, Mahdi; Farrokhpour, Hossein

    2016-06-15

    In this paper, we present the results of an extensive study on a novel approach to the molecular modeling of pure ionic liquids (ILs) that incorporates the perturbed thermodynamic linear Yukawa isotherm regularity (LYIR), which is derived based on an effective nearest neighboring pair attractive interaction of the Yukawa potential. The LYIR was used to model the densities of ILs up to high pressures (35 MPa) and in the temperature range 293.15 to 393.15 K. To use the LYIR for ILs, a simple molecular model was proposed to describe their molecular structure, in which they were considered as a liquid consisting of the ion pairs moving together in the fluid, and each ion pair was assumed to be a one-center spherical united atom. The ILs under consideration contained one of the IL cations [C2mim](+), [C4mim](+), [C7mim](+), [C8mim](+), [C3mpy](+), [C3mpip](+), [C3mpyr](+) or [C4mpyr](+), and one of the IL anions [BF4](-), [C(CN)3](-), [CF3SO4](-) or [NTf2](-). The reliability and physical significance of the parameters as well as the proposed molecular model were tested by calculating the densities of pure imidazolium-, pyridinium-, piperidinium- and pyrrolidimium-based ILs. The results showed that the LYIR can be used to predict and reproduce the density of ILs in good agreement with the experimental data. In addition, the LYIR enabled us to determine the physical quantities, such as an effective Yukawa screening length, λ eff, the product of the effective energy well depth and the effective coordination number, (ε eff/k)z eff, the contribution of the non-reference thermal pressure and also the influence of the anionic and cationic structure on the λ eff parameter. The standard deviation of the IL densities predicted in this work is lower than those calculated by the one other important equation of state reported in the literature. PMID:27157142

  14. Molecular thermodynamic modeling of ionic liquids using the perturbation-based linear Yukawa isotherm regularity

    NASA Astrophysics Data System (ADS)

    Sohrabi Mahboub, Mahdi; Farrokhpour, Hossein

    2016-06-01

    In this paper, we present the results of an extensive study on a novel approach to the molecular modeling of pure ionic liquids (ILs) that incorporates the perturbed thermodynamic linear Yukawa isotherm regularity (LYIR), which is derived based on an effective nearest neighboring pair attractive interaction of the Yukawa potential. The LYIR was used to model the densities of ILs up to high pressures (35 MPa) and in the temperature range 293.15 to 393.15 K. To use the LYIR for ILs, a simple molecular model was proposed to describe their molecular structure, in which they were considered as a liquid consisting of the ion pairs moving together in the fluid, and each ion pair was assumed to be a one-center spherical united atom. The ILs under consideration contained one of the IL cations [C2mim]+, [C4mim]+, [C7mim]+, [C8mim]+, [C3mpy]+, [C3mpip]+, [C3mpyr]+ or [C4mpyr]+, and one of the IL anions [BF4]‑, [C(CN)3]‑, [CF3SO4]‑ or [NTf2]‑. The reliability and physical significance of the parameters as well as the proposed molecular model were tested by calculating the densities of pure imidazolium-, pyridinium-, piperidinium- and pyrrolidimium-based ILs. The results showed that the LYIR can be used to predict and reproduce the density of ILs in good agreement with the experimental data. In addition, the LYIR enabled us to determine the physical quantities, such as an effective Yukawa screening length, λ eff, the product of the effective energy well depth and the effective coordination number, (ε eff/k)z eff, the contribution of the non-reference thermal pressure and also the influence of the anionic and cationic structure on the λ eff parameter. The standard deviation of the IL densities predicted in this work is lower than those calculated by the one other important equation of state reported in the literature.

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

    PubMed

    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.

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

    PubMed

    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.

  17. Potentiometric Sensors Based on Surface Molecular Imprinting: Detection of Cancer Biomarkers and Viruses

    SciTech Connect

    Wang, Y.; Zhang, Z; Jain, V; Yi, J; Mueller, S; Sokolov, J; Liu, Z; Levon, K; Rigas, B; Rafailovich, M

    2010-01-01

    The continuing discovery of cancer biomarkers necessitates improved methods for their detection. Molecular imprinting using artificial materials provides an alternative to the detection of a wide range of substances. We applied surface molecular imprinting using self-assembled monolayers to design sensing elements for the detection of cancer biomarkers and other proteins. These elements consist of a gold-coated silicon chip onto which hydroxyl-terminated alkanethiol molecules and template biomolecule are co-adsorbed, where the thiol molecules are chemically bound to the metal substrate and self-assembled into highly ordered monolayers, the biomolecules can be removed, creating the foot-print cavities in the monolayer matrix for this kind of template molecules. Re-adsorption of the biomolecules to the sensing chip changes its potential, which can be measured potentiometrically. We applied this method to the detection of carcinoembryonic antigen (CEA) in both solutions of purified CEA and in the culture medium of a CEA-producing human colon cancer cell line. The CEA assay, validated also against a standard immunoassay, was both sensitive (detection range 2.5-250 ng/mL) and specific (no cross-reactivity with hemoglobin; no response by a non-imprinted sensor). Similar results were obtained for human amylase. In addition, we detected virions of poliovirus in a specific manner (no cross-reactivity to adenovirus, no response by a non-imprinted sensor). Our findings demonstrate the application of the principles of molecular imprinting to the development of a new method for the detection of protein cancer biomarkers and to protein-based macromolecular structures such as the capsid of a virion. This approach has the potential of generating a general assay methodology that could be highly sensitive, specific, simple and likely inexpensive.

  18. Molecular spintronics based on single-molecule magnets composed of multiple-decker phthalocyaninato terbium(III) complex.

    PubMed

    Katoh, Keiichi; Isshiki, Hironari; Komeda, Tadahiro; Yamashita, Masahiro

    2012-06-01

    Unlike electronics, which is based on the freedom of the charge of an electron whose memory is volatile, spintronics is based on the freedom of the charge, spin, and orbital of an electron whose memory is non-volatile. Although in most GMR, TMR, and CMR systems, bulk or classical magnets that are composed of transition metals are used, this Focus Review considers the growing use of single-molecule magnets (SMMs) that are composed of multinuclear metal complexes and nanosized magnets, which exhibit slow magnetic-relaxation processes and quantum tunneling. Molecular spintronics, which combines spintronics and molecular electronics, is an emerging field of research. Using molecules is advantageous because their electronic and magnetic properties can be manipulated under specific conditions. Herein, recent developments in [LnPc]-based multiple-decker SMMs on surfaces for molecular spintronic devices are presented. First, we discuss the strategies for preparing single-molecular-memory devices by using SMMs. Next, we focus on the switching of the Kondo signal of [LnPc]-based multiple-decker SMMs that are adsorbed onto surfaces, their characterization by using STM and STS, and the relationship between the molecular structure, the electronic structure, and the Kondo resonance of [TbPc(2)]. Finally, the field-effect-transistor (FET) properties of surface-adsorbed [LnPc(2)] and [Ln(2)Pc(3)] cast films are reported, which is the first step towards controlling SMMs through their spins for applications in single-molecular memory and spintronics devices.

  19. Virtual fragment screening: discovery of histamine H3 receptor ligands using ligand-based and protein-based molecular fingerprints.

    PubMed

    Sirci, Francesco; Istyastono, Enade P; Vischer, Henry F; Kooistra, Albert J; Nijmeijer, Saskia; Kuijer, Martien; Wijtmans, Maikel; Mannhold, Raimund; Leurs, Rob; de Esch, Iwan J P; de Graaf, Chris

    2012-12-21

    Virtual fragment screening (VFS) is a promising new method that uses computer models to identify small, fragment-like biologically active molecules as useful starting points for fragment-based drug discovery (FBDD). Training sets of true active and inactive fragment-like molecules to construct and validate target customized VFS methods are however lacking. We have for the first time explored the possibilities and challenges of VFS using molecular fingerprints derived from a unique set of fragment affinity data for the histamine H(3) receptor (H(3)R), a pharmaceutically relevant G protein-coupled receptor (GPCR). Optimized FLAP (Fingerprints of Ligands and Proteins) models containing essential molecular interaction fields that discriminate known H(3)R binders from inactive molecules were successfully used for the identification of new H(3)R ligands. Prospective virtual screening of 156,090 molecules yielded a high hit rate of 62% (18 of the 29 tested) experimentally confirmed novel fragment-like H(3)R ligands that offer new potential starting points for the design of H(3)R targeting drugs. The first construction and application of customized FLAP models for the discovery of fragment-like biologically active molecules demonstrates that VFS is an efficient way to explore protein-fragment interaction space in silico. PMID:23140085

  20. Probing ligand-binding modes and binding mechanisms of benzoxazole-based amide inhibitors with soluble epoxide hydrolase by molecular docking and molecular dynamics simulation.

    PubMed

    Chen, Hang; Zhang, Ying; Li, Liang; Han, Ju-Guang

    2012-08-30

    Soluble epoxide hydrolase (sEH) has become a new therapeutic target for treating a variety of human diseases. The inhibition of human sEH hydrolase activity was studied by molecular docking and molecular dynamics (MD) simulation techniques. A set of six benzoxazole-based amide inhibitors binding to sEH has been studied through molecular docking, MD simulation, free energy calculations, and energy decomposition analysis. On the basis of molecular mechanics-generalized Born/surface area (MM-GB/SA) computation and normal-mode analysis (NMA), the obtained results indicate that the rank of calculated binding free energies (ΔΔGTOT) of these inhibitors is in excellent agreement with that of experimental bioactivity data (IC50). The correlation coefficient (r(2)) between the predicted ΔΔGTOT and IC50 is 0.88. van der Waals energies are the largest component of the total energies, and the entropy changes play an indispensable role in determining the ΔΔGTOT. Rational binding modes were discussed and determined by the docking results and binding free energies. The free energy decomposition of each residue reveals that the residue Trp334 dominates the most binding free energies among all residues and that the activities for these molecules to the sEH are not decided by hydrogen bonds or a certain residue but by the common effect of multiple side chains in the active site.

  1. Ecotope-based entomological surveillance and molecular xenomonitoring of multidrug resistant malaria parasites in anopheles vectors.

    PubMed

    Sorosjinda-Nunthawarasilp, Prapa; Bhumiratana, Adisak

    2014-01-01

    The emergence and spread of multidrug resistant (MDR) malaria caused by Plasmodium falciparum or Plasmodium vivax have become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decrease in vitro and in vivo susceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites in Anopheles vectors is proposed to monitor infection pockets in transmission control areas of forest and forest fringe-related malaria, so as to bridge malaria landscape ecology (ecotope and ecotone) and epidemiology. Malaria ecotope and ecotone are confined to a malaria transmission area geographically associated with the infestation of Anopheles vectors and particular environments to which human activities are related. This enables the EES to encompass mosquito collection and identification, salivary gland DNA extraction, Plasmodium- and species-specific identification, molecular marker-based PCR detection methods for putative drug resistance genes, and data management. The EES establishes strong evidence of Anopheles vectors carrying MDR P. vivax in infection pockets epidemiologically linked with other data obtained during which a course of follow-up treatment of the notified P. vivax patients receiving the first-line treatment was conducted. For regional and global perspectives, the EES would augment the epidemiological surveillance and monitoring of MDR falciparum and vivax malaria

  2. Ecotope-Based Entomological Surveillance and Molecular Xenomonitoring of Multidrug Resistant Malaria Parasites in Anopheles Vectors

    PubMed Central

    2014-01-01

    The emergence and spread of multidrug resistant (MDR) malaria caused by Plasmodium falciparum or Plasmodium vivax have become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decrease in vitro and in vivo susceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites in Anopheles vectors is proposed to monitor infection pockets in transmission control areas of forest and forest fringe-related malaria, so as to bridge malaria landscape ecology (ecotope and ecotone) and epidemiology. Malaria ecotope and ecotone are confined to a malaria transmission area geographically associated with the infestation of Anopheles vectors and particular environments to which human activities are related. This enables the EES to encompass mosquito collection and identification, salivary gland DNA extraction, Plasmodium- and species-specific identification, molecular marker-based PCR detection methods for putative drug resistance genes, and data management. The EES establishes strong evidence of Anopheles vectors carrying MDR P. vivax in infection pockets epidemiologically linked with other data obtained during which a course of follow-up treatment of the notified P. vivax patients receiving the first-line treatment was conducted. For regional and global perspectives, the EES would augment the epidemiological surveillance and monitoring of MDR falciparum and vivax malaria

  3. Determination of protein binding affinities within hydrogel-based molecularly imprinted polymers (HydroMIPs).

    PubMed

    EL-Sharif, Hazim F; Hawkins, Daniel M; Stevenson, Derek; Reddy, Subrayal M

    2014-08-01

    Hydrogel-based molecularly imprinted polymers (HydroMIPs) were prepared for several proteins (haemoglobin, myoglobin and catalase) using a family of acrylamide-based monomers. Protein affinity towards the HydroMIPs was investigated under equilibrium conditions and over a range of concentrations using specific binding with Hill slope saturation profiles. We report HydroMIP binding affinities, in terms of equilibrium dissociation constants (Kd) within the micro-molar range (25 ± 4 μM, 44 ± 3 μM, 17 ± 2 μM for haemoglobin, myoglobin and catalase respectively within a polyacrylamide-based MIP). The extent of non-specific binding or cross-selectivity for non-target proteins has also been assessed. It is concluded that both selectivity and affinity for both cognate and non-cognate proteins towards the MIPs were dependent on the concentration and the complementarity of their structures and size. This is tentatively attributed to the formation of protein complexes during both the polymerisation and rebinding stages at high protein concentrations. We have used atomic force spectroscopy to characterize molecular interactions in the MIP cavities using protein-modified AFM tips. Attractive and repulsive force curves were obtained for the MIP and NIP (non-imprinted polymer) surfaces (under protein loaded or unloaded states). Our force data suggest that we have produced selective cavities for the template protein in the MIPs and we have been able to quantify the extent of non-specific protein binding on, for example, a non-imprinted polymer (NIP) control surface.

  4. A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

    PubMed Central

    2013-01-01

    Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology. PMID:24090398

  5. Ontology based molecular signatures for immune cell types via gene expression analysis

    PubMed Central

    2013-01-01

    Background New technologies are focusing on characterizing cell types to better understand their heterogeneity. With large volumes of cellular data being generated, innovative methods are needed to structure the resulting data analyses. Here, we describe an ‘Ontologically BAsed Molecular Signature’ (OBAMS) method that identifies novel cellular biomarkers and infers biological functions as characteristics of particular cell types. This method finds molecular signatures for immune cell types based on mapping biological samples to the Cell Ontology (CL) and navigating the space of all possible pairwise comparisons between cell types to find genes whose expression is core to a particular cell type’s identity. Results We illustrate this ontological approach by evaluating expression data available from the Immunological Genome project (IGP) to identify unique biomarkers of mature B cell subtypes. We find that using OBAMS, candidate biomarkers can be identified at every strata of cellular identity from broad classifications to very granular. Furthermore, we show that Gene Ontology can be used to cluster cell types by shared biological processes in order to find candidate genes responsible for somatic hypermutation in germinal center B cells. Moreover, through in silico experiments based on this approach, we have identified genes sets that represent genes overexpressed in germinal center B cells and identify genes uniquely expressed in these B cells compared to other B cell types. Conclusions This work demonstrates the utility of incorporating structured ontological knowledge into biological data analysis – providing a new method for defining novel biomarkers and providing an opportunity for new biological insights. PMID:24004649

  6. Systematics of the blindsnakes (Serpentes: Scolecophidia: Typhlopoidea) based on molecular and morphological evidence.

    PubMed

    Pyron, Robert Alexander; Wallach, Van

    2014-01-01

    The blindsnake superfamily Typhlopoidea (Gerrhopilidae, Typhlopidae, and Xenotyphlopidae) is a diverse, widespread part of the global snake fauna. A recent systematic revision based on molecular phylogenetic analyses and some morphological evidence presented a preliminary solution to the non-monophyly of many previously recognized genera, but additional clarification is needed regarding the recognition of some species and genera. We rectify these problems here with a new molecular phylogenetic analysis including 95 of the 275 currently recognized, extant typhlopoids, incorporating both nuclear and mitochondrial loci. We supplement this with data on the external, visceral, and hemipenial morphology of nearly all species to generate a revised classification for Typhlopoidea. Based on morphological data, we re-assign Cathetorhinus from Typhlopidae to Gerrhopilidae. Xenotyphlopidae maintains its current contents (Xenotyphlops). In Typhlopidae, one monotypic genus is synonymized with its larger sister-group as it cannot be unambiguously diagnosed morphologically (Sundatyphlops with Anilios), and two genera are synonymizedwith Typhlops (Antillotyphlops and Cubatyphlops), as they are not reciprocally monophyletic. The genus Asiatyphylops is renamed Argyrophis, the senior synonym for the group. We erect one new genus (Lemuriatyphlops) for a phylogenetically distinct species-group in Asiatyphlopinae. Fourteen of eighteen recognized typhlopid genera are maintained in four subfamilies: Afrotyphlopinae (Afrotyphlops, Grypotyphlops [re-assigned from Asiatyphlopinae], Letheobia, and Rhinotyphlops), Asiatyphlopinae (Acutotyphlops, Anilios, Cyclotyphlops, Indotyphlops, Malayotyphlops, Ramphotyphlops, and Xerotyphlops), Madatyphlopinae (Madatyphlops), and Typhlopinae (Amerotyphlops and Typhlops), some with altered contents. Diagnoses based on morphology are provided for all 19 typhlopoid genera, accounting for all 275 species. This taxonomy provides a robust platform for future

  7. Important issues facing model-based approaches to tunneling transport in molecular junctions

    NASA Astrophysics Data System (ADS)

    Bâldea, Ioan

    Extensive studies on thin films indicated a generic cubic current-voltage $I-V$ dependence as a salient feature of charge transport by tunneling. A quick glance at $I-V$ data for molecular junctions suggests a qualitatively similar behavior. This would render model-based studies almost irrelevant, since, whatever the model, its parameters can always be adjusted to fit symmetric (asymmetric) $I-V$ curves characterized by two (three) expansion coefficients. Here, we systematically examine popular models based on tunneling barrier or tight-binding pictures and demonstrate that, for a quantitative description at biases of interest ($V$ slightly higher than the transition voltage $V_t$), cubic expansions do not suffice. A detailed collection of analytical formulae as well as their conditions of applicability are presented to facilitate experimentalists colleagues to process and interpret their experimental data by obtained by measuring currents in molecular junctions. We discuss in detail the limits of applicability of the various models and emphasize that uncritically adjusting model parameters to experiment may be unjustified because the values deduced in this way may fall in ranges rendering a specific model invalid or incompatible to ab initio estimates. We exemplify with the benchmark case of oligophenylene-based junctions, for which results of ab initio quantum chemical calculations are also reported. As a specific issue, we address the impact of the spatial potential profile and show that it is not notable up to biases V somewhat larger than V_t, unlike at higher biases, where it may be responsible for negative differential resistance effects.

  8. Determination of protein binding affinities within hydrogel-based molecularly imprinted polymers (HydroMIPs).

    PubMed

    EL-Sharif, Hazim F; Hawkins, Daniel M; Stevenson, Derek; Reddy, Subrayal M

    2014-08-01

    Hydrogel-based molecularly imprinted polymers (HydroMIPs) were prepared for several proteins (haemoglobin, myoglobin and catalase) using a family of acrylamide-based monomers. Protein affinity towards the HydroMIPs was investigated under equilibrium conditions and over a range of concentrations using specific binding with Hill slope saturation profiles. We report HydroMIP binding affinities, in terms of equilibrium dissociation constants (Kd) within the micro-molar range (25 ± 4 μM, 44 ± 3 μM, 17 ± 2 μM for haemoglobin, myoglobin and catalase respectively within a polyacrylamide-based MIP). The extent of non-specific binding or cross-selectivity for non-target proteins has also been assessed. It is concluded that both selectivity and affinity for both cognate and non-cognate proteins towards the MIPs were dependent on the concentration and the complementarity of their structures and size. This is tentatively attributed to the formation of protein complexes during both the polymerisation and rebinding stages at high protein concentrations. We have used atomic force spectroscopy to characterize molecular interactions in the MIP cavities using protein-modified AFM tips. Attractive and repulsive force curves were obtained for the MIP and NIP (non-imprinted polymer) surfaces (under protein loaded or unloaded states). Our force data suggest that we have produced selective cavities for the template protein in the MIPs and we have been able to quantify the extent of non-specific protein binding on, for example, a non-imprinted polymer (NIP) control surface. PMID:24950144

  9. Molecular analysis of the human laminin alpha3a chain gene (LAMA3a): a strategy for mutation identification and DNA-based prenatal diagnosis in Herlitz junctional epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Cserhalmi-Friedman, P B; Tang, M; Ryan, M C; Uitto, J; Christiano, A M

    1998-09-01

    Mutations in the genes (LAMA3, LAMB3, and LAMC2) encoding the subunit polypeptides of the cutaneous basement membrane zone protein laminin 5 have been reported in different forms of junctional epidermolysis bullosa (JEB), an inherited blistering skin disease. In this study, we present the complete exon-intron organization of the "a" transcript of the laminin alpha3 chain gene, LAMA3a, which is expressed primarily in the skin. We have performed fine-resolution mapping of this gene on chromosome 18q11.2 using a human-hamster radiation hybrid panel. We have also developed a mutation-detection strategy based on the exon-intron structure of LAMA3a. This strategy, based on PCR amplification of genomic sequences, followed by heteroduplex scanning and automated nucleotide sequencing, was used for successful mutation screening in a family with the lethal (Herlitz) type of JEB, and two novel LAMA3 mutations were identified in the proband. The mutations consisted of a single-base pair deletion in LAMA3a exon A11 on the paternal allele, designated 1239delC, and a two-base pair deletion in LAMA3a exon A23 on the maternal allele, designated 2959delGG. This information was also used for DNA-based prenatal testing in a subsequent pregnancy in this family. Collectively, these results attest to our expanding capability to elucidate the genetic basis of various forms of epidermolysis bullosa using molecular techniques. PMID:9759651

  10. Between algorithm and model: different Molecular Surface definitions for the Poisson-Boltzmann based electrostatic characterization of biomolecules in solution.

    PubMed

    Decherchi, Sergio; Colmenares, José; Catalano, Chiara Eva; Spagnuolo, Michela; Alexov, Emil; Rocchia, Walter

    2013-01-01

    The definition of a molecular surface which is physically sound and computationally efficient is a very interesting and long standing problem in the implicit solvent continuum modeling of biomolecular systems as well as in the molecular graphics field. In this work, two molecular surfaces are evaluated with respect to their suitability for electrostatic computation as alternatives to the widely used Connolly-Richards surface: the blobby surface, an implicit Gaussian atom centered surface, and the skin surface. As figures of merit, we considered surface differentiability and surface area continuity with respect to atom positions, and the agreement with explicit solvent simulations. Geometric analysis seems to privilege the skin to the blobby surface, and points to an unexpected relationship between the non connectedness of the surface, caused by interstices in the solute volume, and the surface area dependence on atomic centers. In order to assess the ability to reproduce explicit solvent results, specific software tools have been developed to enable the use of the skin surface in Poisson-Boltzmann calculations with the DelPhi solver. Results indicate that the skin and Connolly surfaces have a comparable performance from this last point of view.

  11. Analysis of low molecular weight metabolites in tea using mass spectrometry-based analytical methods.

    PubMed

    Fraser, Karl; Harrison, Scott J; Lane, Geoff A; Otter, Don E; Hemar, Yacine; Quek, Siew-Young; Rasmussen, Susanne

    2014-01-01

    Tea is the second most consumed beverage in the world after water and there are numerous reported health benefits as a result of consuming tea, such as reducing the risk of cardiovascular disease and many types of cancer. Thus, there is much interest in the chemical composition of teas, for example; defining components responsible for contributing to reported health benefits; defining quality characteristics such as product flavor; and monitoring for pesticide residues to comply with food safety import/export requirements. Covered in this review are some of the latest developments in mass spectrometry-based analytical techniques for measuring and characterizing low molecular weight components of tea, in particular primary and secondary metabolites. The methodology; more specifically the chromatography and detection mechanisms used in both targeted and non-targeted studies, and their main advantages and disadvantages are discussed. Finally, we comment on the latest techniques that are likely to have significant benefit to analysts in the future, not merely in the area of tea research, but in the analytical chemistry of low molecular weight compounds in general. PMID:24499071

  12. Multispectral excitation based multiple fluorescent targets resolving in fluorescence molecular tomography

    NASA Astrophysics Data System (ADS)

    Zhou, Yuan; Guang, Huizhi; Pu, Huangsheng; Zhang, Jiulou; Bai, Jing; Luo, Jianwen

    2016-04-01

    Fluorescence molecular tomography (FMT) can visualize biological activities at cellular and molecular levels in vivo, and has been extensively used in drug delivery and tumor detection research of small animals. The ill-posedness of the FMT inverse problem makes it difficult to reconstruct and resolve multiple adjacent fluorescent targets that have different functional features but are labeled with the same fluorochrome. An algorithm based on independent component analysis (ICA) for multispectral excited FMT is proposed to resolve multiple fluorescent targets in this study. Fluorescent targets are excited by multispectral excitation, and the three-dimensional distribution of fluorescent yields under the excitation spectrum is reconstructed by an iterative Tikhonov regularization algorithm. Subsequently, multiple fluorescent targets are resolved from mixed fluorescence signals by employing ICA. Simulations were performed and the results demonstrate that multiple adjacent fluorescent targets can be resolved if the number of excitation wavelengths is not smaller than that of fluorescent targets with different concentrations. The algorithm obtains both independent components that provide spatial information of different fluorescent targets and spectral courses that reflect variation trends of fluorescent yields along with the excitation spectrum. By using this method, it is possible to visualize the metabolism status of drugs in different structure organs, and quantitatively depict the variation trends of fluorescent yields of each functional organ under the excitation spectrum. This method may provide a pattern for tumor detection, drug delivery and treatment monitoring in vivo.

  13. Structural changes in a Schiff base molecular assembly initiated by scanning tunneling microscopy tip.

    PubMed

    Tomak, A; Bacaksiz, C; Mendirek, G; Sahin, H; Hur, D; Görgün, K; Senger, R T; Birer, Ö; Peeters, F M; Zareie, H M

    2016-08-19

    We report the controlled self-organization and switching of newly designed Schiff base (E)-4-((4-(phenylethynyl) benzylidene) amino) benzenethiol (EPBB) molecules on a Au (111) surface at room temperature. Scanning tunneling microscopy and spectroscopy (STM/STS) were used to image and analyze the conformational changes of the EPBB molecules. The conformational change of the molecules was induced by using the STM tip while increasing the tunneling current. The switching of a domain or island of molecules was shown to be induced by the STM tip during scanning. Unambiguous fingerprints of the switching mechanism were observed via STM/STS measurements. Surface-enhanced Raman scattering was employed, to control and identify quantitatively the switching mechanism of molecules in a monolayer. Density functional theory calculations were also performed in order to understand the microscopic details of the switching mechanism. These calculations revealed that the molecular switching behavior stemmed from the strong interaction of the EPBB molecules with the STM tip. Our approach to controlling intermolecular mechanics provides a path towards the bottom-up assembly of more sophisticated molecular machines. PMID:27378765

  14. Self-Assembly of Polyhedral Oligomeric Silsesquioxane-Based Giant Molecular Shape Amphiphiles

    NASA Astrophysics Data System (ADS)

    Li, Yiwen; Cheng, Stephen

    2013-03-01

    A series of giant molecular shape amphiphiles based on functional polyhedral oligomeric silsesquioxane (POSS) particles was designed and synthesized. The supramolecualr structures of these assemblies along with the resulting ordered structures are fully investigated to determine their structure-property relationships. For example, functional POSS cages with different surface chemistry and sizes were employed to construct dumbbell- and snowman-like molecular Janus particles with various symmetry breakings. These particles could self-organize into hierarchically ordered supramolecular structures in the bulk. Another illustrating example is a series of novel giant surfactants, lipids and gemini surfactants possessing a hydrophilic POSS head and polymer or alkyl chain tails. Diverse architectures of this class of materials have been constructed and their self-assembly processes in solution and bulk state have been discussed. This set of research results not only has general implications in the basic physical principles underlying their self-assembly behaviors, but also create unique materials for developing advanced technologies by combining the properties of hybrid materials

  15. Anisotropy induced Kondo splitting in a mechanically stretched molecular junction: A first-principles based study.

    PubMed

    Wang, Xiaoli; Hou, Dong; Zheng, Xiao; Yan, YiJing

    2016-01-21

    The magnetic anisotropy and Kondo phenomena in a mechanically stretched magnetic molecular junction are investigated by combining the density functional theory (DFT) and hierarchical equations of motion (HEOM) approach. The system is comprised of a magnetic complex Co(tpy-SH)2 sandwiched between adjacent gold electrodes, which is mechanically stretched in experiments done by Parks et al. [Science 328, 1370 (2010)]. The electronic structure and mechanical property of the stretched system are investigated via the DFT calculations. The HEOM approach is then employed to characterize the Kondo resonance features, based on the Anderson impurity model parameterized from the DFT results. It is confirmed that the ground state prefers the S = 1 local spin state. The structural properties, the magnetic anisotropy, and corresponding Kondo peak splitting in the axial stretching process are systematically evaluated. The results reveal that the strong electron correlations and the local magnetic properties of the molecule magnet are very sensitive to structural distortion. This work demonstrates that the combined DFT+HEOM approach could be useful in understanding and designing mechanically controlled molecular junctions.

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

    PubMed

    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.

  17. Molecular Description of Macroorchis spinulosus (Digenea: Nanophyetidae) Based on ITS1 Sequences

    PubMed Central

    Won, Eun Jeong; Kim, Deok-Gyu; Cho, Jaeeun; Jung, Bong-Kwang; Kim, Min-Jae; Yun, Yong Woon; Chai, Jong-Yil; Ryang, Dong Wook

    2016-01-01

    We performed a molecular genetic study on the sequences of 18S ribosomal RNA (ITS1 region) gene in 4-day-old adult worms of Macroorchis spinulosus recovered in mice experimentally infected with metacercariae from crayfish in Jeollanam-do Province, Korea. The metacercariae were round, 180 μm in average diameter, encysted with 2 layers of thick walls, but the stylet on the oral sucker was not clearly seen. The adult flukes were oval shape, and 760-820 μm long and 320-450 μm wide, with anterolateral location of 2 large testes. The phylogenetic tree based on ITS1 sequences of 6 M. spinulosus samples showed their distinguished position from other trematode species in GenBank. The most closely resembled group was Paragonimus spp. which also take crayfish or crabs as the second intermediate host. The present study is the first molecular characterization of M. spinulosus and provided a basis for further phylogenetic studies to compare with other trematode fauna in Korea. PMID:26951989

  18. A Study on the Structure and Photodetachment Dynamics of Copper Based Molecular Anions Using Photoelectron Spectroscopy

    NASA Astrophysics Data System (ADS)

    Holtgrewe, Nicholas Stephen

    This dissertation represents a study of the effects of electron molecule interactions in the detachment and dissociation dynamics of copper based molecular anions. Results are presented on the photodetachment of small copper oxide CuOn-- (n = 1, 2) and copper fluoride CuFn-- (n = 1, 2) molecular anions. Effects of different resonances are explored using the photoelectron angular distributions (PADs) and the relative intensity variations in vibrational channel cross sections. The specific resonances studied include dipole bound resonances, in which the electric dipole moment of the neutral molecule captures the outgoing electron, and electronic Feshbach resonances, in which the anion undergoes absorption to an excited anion state (lying energetically above the neutral) followed by relaxation via autodetachment into the electronic continuum. In addition to electron scattering resonances, the effects of dissociation dynamics on linear CuO2-- are studied, wherein the linear anion isomer was found to dissociate to Cu-- fragments. This dissociation process is interpreted with experimental data acquired from nanosecond photoelectron images and a femtosecond time resolved study.

  19. Enabling Metabolomics Based Biomarker Discovery Studies Using Molecular Phenotyping of Exosome-Like Vesicles

    PubMed Central

    Altadill, Tatiana; Campoy, Irene; Lanau, Lucia; Gill, Kirandeep; Rigau, Marina; Gil-Moreno, Antonio; Reventos, Jaume; Byers, Stephen; Colas, Eva; Cheema, Amrita K.

    2016-01-01

    Identification of sensitive and specific biomarkers with clinical and translational utility will require smart experimental strategies that would augment expanding the breadth and depth of molecular measurements within the constraints of currently available technologies. Exosomes represent an information rich matrix to discern novel disease mechanisms that are thought to contribute to pathologies such as dementia and cancer. Although proteomics and transcriptomic studies have been reported using Exosomes-Like Vesicles (ELVs) from different sources, exosomal metabolome characterization and its modulation in health and disease remains to be elucidated. Here we describe methodologies for UPLC-ESI-MS based small molecule profiling of ELVs from human plasma and cell culture media. In this study, we present evidence that indeed ELVs carry a rich metabolome that could not only augment the discovery of low abundance biomarkers but may also help explain the molecular basis of disease progression. This approach could be easily translated to other studies seeking to develop predictive biomarkers that can subsequently be used with simplified targeted approaches. PMID:26974972

  20. DNA molecular beacon-based plastic biochip: a versatile and sensitive scanometric detection platform.

    PubMed

    Shi, Xiaoli; Wen, Jing; Li, Yunchao; Zheng, Yue; Zhou, Jianjun; Li, Xiaohong; Yu, Hua-Zhong

    2014-12-24

    In this paper, we report a novel DNA molecular beacon (MB)-based plastic biochip platform for scanometric detection of a range of analytical targets. Hairpin DNA strands, which are dually modified with amino and biotin groups at their two ends are immobilized on a disposable plastic (polycarbonate) substrate as recognition element and gold nanoparticle-assisted silver-staining as signal reading protocol. Initially, the immobilized DNA probes are in their folded forms; upon target binding the hairpin secondary structure of the probe strand is "forced" open (i.e., converted to the unfolded state). Nanogold-streptavidin conjugates can then bind the terminal biotin groups and promote the deposition of rather large silver particles which can be either directly visualized or quantified with a standard flatbed scanner. We demonstrate that with properly designed probe sequences and optimized preparation conditions, a range of molecular targets, such as DNA strands, proteins (thrombin) and heavy metal ions (Hg(2+)), can be detected with high sensitivity and excellent selectivity. The detection can be done in both standard physiological buffers and real world samples. This constitutes a platform technology for performing rapid, sensitive, cost-effective, and point-of-care (POC) chemical analysis and medical diagnosis.

  1. Molecular Description of Macroorchis spinulosus (Digenea: Nanophyetidae) Based on ITS1 Sequences.

    PubMed

    Won, Eun Jeong; Kim, Deok-Gyu; Cho, Jaeeun; Jung, Bong-Kwang; Kim, Min-Jae; Yun, Yong Woon; Chai, Jong-Yil; Ryang, Dong Wook

    2016-02-01

    We performed a molecular genetic study on the sequences of 18S ribosomal RNA (ITS1 region) gene in 4-day-old adult worms of Macroorchis spinulosus recovered in mice experimentally infected with metacercariae from crayfish in Jeollanam-do Province, Korea. The metacercariae were round, 180 μm in average diameter, encysted with 2 layers of thick walls, but the stylet on the oral sucker was not clearly seen. The adult flukes were oval shape, and 760-820 μm long and 320-450 μm wide, with anterolateral location of 2 large testes. The phylogenetic tree based on ITS1 sequences of 6 M. spinulosus samples showed their distinguished position from other trematode species in GenBank. The most closely resembled group was Paragonimus spp. which also take crayfish or crabs as the second intermediate host. The present study is the first molecular characterization of M. spinulosus and provided a basis for further phylogenetic studies to compare with other trematode fauna in Korea. PMID:26951989

  2. Molecular probes based on microstructured fibers and surface enhanced Raman scattering

    NASA Astrophysics Data System (ADS)

    Zhang, Yi; Shi, Chao; Gu, Claire; Seballos, Leo; Schwartzberg, Adam; Zhang, Jin Z.; Chen, Bin

    2007-09-01

    In recent years, there has been significant interest in using surface enhanced Raman scattering (SERS) and optical fibers for chemical, biological, and environmental detections. The combination of SERS and optical fibers offers the advantages of the molecular specificity of Raman scattering, huge enhancement factor of SERS, and flexibility of optical fibers. In this paper, we report our work on the development of fiber biosensors based on SERS emphasizing on recent progress in the fabrication of photonic crystal fiber (PCF) SERS sensors for highly sensitive molecular detection. To increase the sensitivity, one needs to increase either the excitation laser power or the amount of analyte molecules in the active region of the sensor. The high excitation intensity is not desirable for biosensors due to the low damage threshold of live tissues or bio-molecules. In our investigation of various fiber configurations, hollow core (HC) PCFs show the greatest advantages over all other types of fiber probes because of the large contact area. The hollow core nature allows the analytes and SERS substrate to fill the inner surface of the air channels. In addition, by sealing the cladding holes of the HCPCF, only the central hole will be open and filled with liquid samples. As both the light and the sample are confined in the fiber core, the sensitivity is significantly improved. The newly developed liquid core PCF sensor was tested in the detection of rhodamine 6G (R6G), human insulin, and tryptophan with good sensitivity due to the enhanced interaction volume.

  3. Molecular-Based Theory for Electron-Transfer Reorganization Energy in Solvent Mixtures.

    PubMed

    Zhuang, Bilin; Wang, Zhen-Gang

    2016-07-01

    Using statistical-field techniques, we develop a molecular-based dipolar self-consistent-field theory (DSCFT) for charge solvation in liquid mixtures under equilibrium and nonequilibrium conditions, and apply it to compute the solvent reorganization energy of electron-transfer reactions. In addition to the nonequilibrium orientational polarization, the reorganization energy in liquid mixtures is also determined by the out-of-equilibrium solvent composition around the reacting species due to preferential solvation. Using molecular parameters that are readily available, the DSCFT naturally accounts for the dielectric saturation effect and the spatially varying solvent composition in the vicinity of the reacting species. We identify three general categories of binary solvent mixtures, classified by the relative optical and static dielectric permittivities of the solvent components. Each category of mixture is shown to produce a characteristic local solvent composition profile in the vicinity of the reacting species, which gives rise to the distinctive composition dependence of the reorganization energy that cannot be predicted using the dielectric permittivities of the homogeneous solvent mixtures. PMID:27187110

  4. Electrochemical sensor for sulfadimethoxine based on molecularly imprinted polypyrrole: study of imprinting parameters.

    PubMed

    Turco, Antonio; Corvaglia, Stefania; Mazzotta, Elisabetta

    2015-01-15

    The present work describes the development of a simple and cost-effective electrochemical sensor for sulfadimethoxine (SDM) based on molecularly imprinted overoxidized polypyrrole (PPy). An all electrochemical approach is used for sensor fabrication and application consisting in molecularly imprinted polymer (MIP) galvanostatic deposition on a gold electrode and its overoxidation under different experimental conditions and in SDM amperometric detection. Several parameters influencing the imprinting effect are critically discussed and evaluated. A key role of the electrolyte used in electropolymerization (tetrabuthylammonium perchlorate and lithium perchlorate) has emerged demonstrating its effect on sensing performances of imprinted PPy and, related to this, on its morphology, as highlighted by atomic force microscopy (AFM). The effect of different overoxidation conditions in removing template is evaluated by analyzing MIP films before and after the treatment by X-ray photoelectron spectroscopy (XPS) also evidencing the correlation between MIP chemical structure and its rebinding ability. MIP-template interaction is verified also by Fourier Transform Infrared (FT-IR) spectroscopy. Under the selected optimal conditions, MIP sensor shows a linear range from 0.15 to 3.7 mM SDM, a limit of detection of 70 μM, a highly reproducible response (RSD 4.2%) and a good selectivity in the presence of structurally related molecules. SDM was determined in milk samples spiked at two concentration levels: 0.2 mM and 0.4 mM obtaining a satisfactory recovery of (97±3)% and (96±8)%, respectively.

  5. Xanthine microsensor based on polypyrrole molecularly imprinted film modified carbon fiber microelectrodes.

    PubMed

    Liu, Bin; Wang, Xiao-Li; Lian, Hui-Ting; Sun, Xiang-Ying

    2013-09-15

    A molecularly imprinted polymers (MIPs) microsensor was presented as a carbon fiber microelectrode (CFME) coating for specifically recognizing xanthine (Xan). The polymeric film was obtained based on the imprinted procedure of electropolymerization of pyrrole in the presence of the template molecule Xan by cyclic voltammetry, and template was removed by magnetic stirring. Under the optimum conditions, a satisfactory molecularly binding selectivity of Xan was obtained from the MIPs microsensor with an imprinting factor (IF) of 6.63 and a linear response to concentration in certain ranges. The ranges are from 4.0 × 10⁻⁶ to 6.0 × 10⁻⁵ M and from 8.0 × 10⁻⁵ to 2.0 × 10⁻³ M with a detection limit of 2.5 × 10⁻⁷ M. Meanwhile, good stability (relative standard deviation [RSD] = 3.2%, n = 10) and reproducibility (RSD = 2.0%, n = 10) were observed, and recoveries ranging from 96.9 to 102.5% were calculated when applied to Xan determination in real blood serum samples.

  6. Low-Molecular-Weight Organo- and Hydrogelators Based on Cyclo(l-Lys-l-Glu).

    PubMed

    Geng, Huimin; Ye, Lin; Zhang, Ai-Ying; Li, Jingbo; Feng, Zeng-Guo

    2016-05-10

    Four cyclo(l-Lys-l-Glu) derivatives (3-6) were synthesized from the coupling reaction of protecting l-lysine with l-glutamic acid followed by the cyclization, deprotection, and protection reactions. They can efficiently gelate a wide variety of organic solvents or water. Interestingly, a spontaneous chemical reaction proceeded in the organogel obtained from 3 in acetone exhibiting not only visual color alteration but also increasing mechanical strength with the progress of time due to the formation of Schiff base. Moreover, 6 bearing a carboxylic acid and Fmoc group displayed a robust hydrogelation capability in PBS solution. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed the characteristic gelation morphologies of 3D fibrous network structures in the resulting organo- and hydrogels. FT-IR and fluorescence analyses indicated that the hydrogen bonding and π-π stacking play as major driving forces for the self-assembly of these cyclic dipeptides as low-molecular-weight gelators. X-ray diffraction (XRD) measurements and computer modeling provided information on the molecular packing model in the hydrogelation state of 6. A spontaneous chemical reaction proceeded in the organogel obtained from 3 in acetone exhibiting visual color alteration and increasing mechanical strength. 6 bearing an optimized balance of hydrophilicity to lipophilicity gave rise to a hydrogel in PBS with MGC at 1 mg/mL. PMID:27101967

  7. Immobilization of aptamer-based molecular beacons onto optically-encoded micro-sized beads.

    PubMed

    Jun, Bong-Hyun; Kim, Ji-Eun; Rho, Chul; Byun, Jang-Woong; Kim, Yo Han; Kang, Homan; Kim, Jong-Ho; Kang, Taegyu; Cho, Myung-Haing; Lee, Yoon-Sik

    2011-07-01

    This paper presents a method for the novel immobilization of aptamer-based molecular beacons (apta-beacons) onto optically-encoded micro-sized beads (apta-beacon beads). To immobilize apta-beacons onto flourescently-encoded micro-sized beads, core-shell type beads containing a fluorescent dye-encoded core and apta beacon-coupled shell were prepared. The fluorescent dye-encoded beads were prepared from TentaGel resins by coupling RITC to the amino groups of the core region, after partial protection of amino groups with Fmoc-OSu in a diffusion-controlled manner. After deprotection of the Fmoc-amino groups, FITC-coupled molecular beacons (MBs) were immobilized to the beads together with a quencher by covelent bonding. Briefly, aspartic acid (Asp) was coupled to the shell part of the beads. Then, the quencher was coupled to the N-terminal amino group of Asp and the MBs were coupled to the side chain carboxyl group. In a model study, thrombin was directly detected using this apta-beacon bead method. The thrombin-bound apta-beacon beads were easily recognized by the appearance of fluorescence without any further labeling step.

  8. Tris-thiourea tripodal-based molecules as chloride transmembrane transporters: insights from molecular dynamics simulations.

    PubMed

    Marques, Igor; Colaço, Ana R; Costa, Paulo J; Busschaert, Nathalie; Gale, Philip A; Félix, Vítor

    2014-05-28

    The interaction of six tripodal synthetic chloride transmembrane transporters with a POPC bilayer was investigated by means of molecular dynamics simulations using the general Amber force field (GAFF) for the transporters and the LIPID11 force field for phospholipids. These transporters are structurally simple molecules, based on the tris(2-aminoethyl)amine scaffold, containing three thiourea binding units coupled with three n-butyl (1), phenyl (2), fluorophenyl (3), pentafluorophenyl (4), trifluoromethylphenyl (5), or bis(trifluoromethyl)phenyl (6) substituents. The passive diffusion of 1-6⊃ Cl(-) was evaluated with the complexes initially positioned either in the water phase or inside the bilayer. In the first scenario the chloride is released in the water solution before the synthetic molecules achieve the water-lipid interface and permeate the membrane. In the latter one, only when the chloride complex reaches the interface is the anion released to the water phase, with the transporter losing the initial ggg tripodal shape. Independently of the transporter used in the membrane system, the bilayer structure is preserved and the synthetic molecules interact with the POPC molecules at the phosphate headgroup level, via N-H···O hydrogen bonds. Overall, the molecular dynamics simulations' results indicate that the small tripodal molecules in this series have a low impact on the bilayer and are able to diffuse with chloride inside the lipid environment. Indeed, these are essential conditions for these molecules to promote the transmembrane transport as anion carriers, in agreement with experimental efflux data. PMID:24663079

  9. Molecular quantum spintronics: supramolecular spin valves based on single-molecule magnets and carbon nanotubes.

    PubMed

    Urdampilleta, Matias; Nguyen, Ngoc-Viet; Cleuziou, Jean-Pierre; Klyatskaya, Svetlana; Ruben, Mario; Wernsdorfer, Wolfgang

    2011-01-01

    We built new hybrid devices consisting of chemical vapor deposition (CVD) grown carbon nanotube (CNT) transistors, decorated with TbPc(2) (Pc = phthalocyanine) rare-earth based single-molecule magnets (SMMs). The drafting was achieved by tailoring supramolecular π-π interactions between CNTs and SMMs. The magnetoresistance hysteresis loop measurements revealed steep steps, which we can relate to the magnetization reversal of individual SMMs. Indeed, we established that the electronic transport properties of these devices depend strongly on the relative magnetization orientations of the grafted SMMs. The SMMs are playing the role of localized spin polarizer and analyzer on the CNT electronic conducting channel. As a result, we measured magneto-resistance ratios up to several hundred percent. We used this spin valve effect to confirm the strong uniaxial anisotropy and the superparamagnetic blocking temperature (T(B) ~ 1 K) of isolated TbPc(2) SMMs. For the first time, the strength of exchange interaction between the different SMMs of the molecular spin valve geometry could be determined. Our results introduce a new design for operable molecular spintronic devices using the quantum effects of individual SMMs.

  10. A fiber-optic evanescent wave DNA biosensor based on novel molecular beacons.

    PubMed

    Liu, X; Tan, W

    1999-11-15

    We have prepared a novel optical fiber evanescent wave DNA biosensor using a newly developed molecular beacon DNA probe. The molecular beacons (MB) are oligonucleotide probes that become fluorescent upon hybridization with target DNA/RNA molecules. Biotinylated MBs have been designed and immobilized on an optical fiber core surface via biotin-avidin or biotin-streptavidin interactions. The DNA sensor based on a MB does not need labeled analyte or intercalation reagents. It can be used to directly detect, in real-time, target DNA/RNA molecules without using competitive assays. The sensor is rapid, stable, highly selective, and reproducible. We have studied the hybridization kinetics of the immobilized MB by changing the ionic strength of the hybridization solution and target DNA concentration. Our result shows divalent cations play a more important role than monovalent cations in stabilizing the MB stem hybrids and in accelerating the hybridization reaction with target DNA/RNA molecules. The concentration detection limit of the MB evanescent wave biosensor is 1.1 nM. The MB DNA biosensor has been applied to the analysis of specific gamma-actin mRNA sequences amplified by polymerase chain reaction.

  11. A novel reconfigurable optical biosensor based on DNA aptamers and a DNA molecular beacon.

    PubMed

    Buranachai, Chittanon; Thavarungkul, Panote; Kanatharana, Proespichaya

    2012-11-01

    In order to alter a typical molecular aptamer beacon (MAB) to detect a different analyte there is currently a need to change the whole sensor unit including the expensive labeling fluorophores. In this work a DNA-based reconfigurable molecular aptamer beacon was developed. It is composed of two parts: a variable part and a constant part. The variable part comprises an aptamer strand and its complementary strand while the constant part is an oligonucleotide doubly labeled with a Förster Resonance Energy Transfer (FRET) pair and the two parts become joined via DNA hybridization. The sensor exists in two conformations: a folded (high FRET) and an unfolded (low FRET) in the absence and presence of the aptamer-target binding respectively. This sensor can be reconfigured by washing away the aptamer and the complementary strand using proper complementary strands, called washers. As a proof of the principle, a sensor that bound the enzyme thrombin, an analyte with a strong binding, was first constructed and then reconfigured to bind adenosine, selected as an analyte with a weak binding. We believe that the design is of universal use applicable to many types of aptamers.

  12. Structural changes in a Schiff base molecular assembly initiated by scanning tunneling microscopy tip

    NASA Astrophysics Data System (ADS)

    Tomak, A.; Bacaksiz, C.; Mendirek, G.; Sahin, H.; Hur, D.; Görgün, K.; Senger, R. T.; Birer, Ö.; Peeters, F. M.; Zareie, H. M.

    2016-08-01

    We report the controlled self-organization and switching of newly designed Schiff base (E)-4-((4-(phenylethynyl) benzylidene) amino) benzenethiol (EPBB) molecules on a Au (111) surface at room temperature. Scanning tunneling microscopy and spectroscopy (STM/STS) were used to image and analyze the conformational changes of the EPBB molecules. The conformational change of the molecules was induced by using the STM tip while increasing the tunneling current. The switching of a domain or island of molecules was shown to be induced by the STM tip during scanning. Unambiguous fingerprints of the switching mechanism were observed via STM/STS measurements. Surface-enhanced Raman scattering was employed, to control and identify quantitatively the switching mechanism of molecules in a monolayer. Density functional theory calculations were also performed in order to understand the microscopic details of the switching mechanism. These calculations revealed that the molecular switching behavior stemmed from the strong interaction of the EPBB molecules with the STM tip. Our approach to controlling intermolecular mechanics provides a path towards the bottom-up assembly of more sophisticated molecular machines.

  13. Diagnosing rejection in renal transplants: a comparison of molecular- and histopathology-based approaches.

    PubMed

    Reeve, J; Einecke, G; Mengel, M; Sis, B; Kayser, N; Kaplan, B; Halloran, P F

    2009-08-01

    The transcriptome has considerable potential for improving biopsy diagnoses. However, to realize this potential the relationship between the molecular phenotype of disease and histopathology must be established. We assessed 186 consecutive clinically indicated kidney transplant biopsies using microarrays, and built a classifier to distinguish rejection from nonrejection using predictive analysis of microarrays (PAM). Most genes selected by PAM were interferon-gamma-inducible or cytotoxic T-cell associated, for example, CXCL9, CXCL11, GBP1 and INDO. We then compared the PAM diagnoses to those from histopathology, which are based on the Banff diagnostic criteria. Disagreement occurred in approximately 20% of diagnoses, principally because of idiosyncratic limitations in the histopathology scoring system. The problematic diagnosis of 'borderline rejection' was resolved by PAM into two distinct classes, rejection and nonrejection. The diagnostic discrepancies between Banff and PAM in these cases were largely due to the Banff system's requirement for a tubulitis threshold in defining rejection. By examining the discrepancies between gene expression and histopathology, we provide external validation of the main features of the histopathology diagnostic criteria (the Banff consensus system), recommend improvements and outline a pathway for introducing molecular measurements.

  14. Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology.

    PubMed

    Gao, Li; Wang, Xiao-Dong; Niu, Yang-Yang; Duan, Dan-Dan; Yang, Xue; Hao, Jian; Zhu, Cui-Hong; Chen, Dan; Wang, Ke-Xin; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-05-04

    Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan-Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc.

  15. Terahertz spectra of biotin based on first principle, molecular mechanical, and hybrid simulations.

    PubMed

    Bykhovski, Alexei; Woolard, Dwight

    2013-07-01

    Terahertz (THz) absorption of biotin was simulated using the first principle and the density functional theory (DFT) both in the harmonic approximation and with corrections for the anharmonicity. Anharmonicity corrections were calculated using two different approaches. First, the perturbation theory-based first principle calculations were performed to include third- and fourth-order anharmonicity corrections in atomic displacements to harmonic vibrational states. Second, the atom-centered density matrix propagation molecular dynamics model that provides a good energy conservation was used to calculate the atomic trajectories, velocities, and a dipole moment time history of biotin at low and room temperatures. Predicted low-THz lines agree well with the experimental spectra. The influence of the polyethylene (PE) matrix embedment on the THz spectra of biotin at the nanoscale was studied using the developed hybrid DFT/molecular mechanical approach. While PE is almost transparent at THz frequencies, additional low-THz lines are predicted in the biotin/PE system, which reflects a dynamic interaction between biotin and a surrounding PE cavity.

  16. Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology

    PubMed Central

    Gao, Li; Wang, Xiao-dong; Niu, Yang-yang; Duan, Dan-dan; Yang, Xue; Hao, Jian; Zhu, Cui-hong; Chen, Dan; Wang, Ke-xin; Qin, Xue-mei; Wu, Xiong-zhi

    2016-01-01

    Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan–Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc. PMID:27143508

  17. Phylogeny of the Archiborborinae (Diptera: Sphaeroceridae) Based on Combined Morphological and Molecular Analysis

    PubMed Central

    Kits, Joel H.; Marshall, Stephen A.; Skevington, Jeffrey H.

    2013-01-01

    The Archiborborinae is a diverse Neotropical subfamily of Sphaeroceridae, with many undescribed species. The existing generic classification includes three genera consisting of brachypterous species, with all other species placed in the genus Archiborborus. We present the first phylogenetic hypothesis for the subfamily based on morphological, molecular, and combined datasets. Morphological data include 53 characters and cover all valid described taxa (33 species in 4 genera) in the subfamily, as well as 83 undescribed species. Molecular data for five genes (mitochondrial 12S rDNA, cytochrome c oxidase subunit I, and cytochrome B, and nuclear alanyl-tRNA synthetase and 28S rDNA) were obtained for 21 ingroup taxa. Data support the separation of the Archiborborinae from the Copromyzinae, with which they were formerly combined. Analyses support consistent groups within the subfamily, but relationships between groups are poorly resolved. The validity of the brachypterous genera Penola Richards and Frutillaria Richards is supported. The former genus Archiborborus Duda is paraphyletic, and will be divided into monophyletic genera on the basis of this work. Aptery and brachyptery have evolved multiple times in the subfamily. Antrops Enderlein, previously including a single brachypterous species, is a senior synonym of Archiborborus. PMID:23349671

  18. Hierarchical Conformational Analysis of Native Lysozyme Based on Sub-Millisecond Molecular Dynamics Simulations

    PubMed Central

    Wang, Kai; Long, Shiyang; Tian, Pu

    2015-01-01

    Hierarchical organization of free energy landscape (FEL) for native globular proteins has been widely accepted by the biophysics community. However, FEL of native proteins is usually projected onto one or a few dimensions. Here we generated collectively 0.2 milli-second molecular dynamics simulation trajectories in explicit solvent for hen egg white lysozyme (HEWL), and carried out detailed conformational analysis based on backbone torsional degrees of freedom (DOF). Our results demonstrated that at micro-second and coarser temporal resolutions, FEL of HEWL exhibits hub-like topology with crystal structures occupying the dominant structural ensemble that serves as the hub of conformational transitions. However, at 100ns and finer temporal resolutions, conformational substates of HEWL exhibit network-like topology, crystal structures are associated with kinetic traps that are important but not dominant ensembles. Backbone torsional state transitions on time scales ranging from nanoseconds to beyond microseconds were found to be associated with various types of molecular interactions. Even at nanoseconds temporal resolution, the number of conformational substates that are of statistical significance is quite limited. These observations suggest that detailed analysis of conformational substates at multiple temporal resolutions is both important and feasible. Transition state ensembles among various conformational substates at microsecond temporal resolution were observed to be considerably disordered. Life times of these transition state ensembles are found to be nearly independent of the time scales of the participating torsional DOFs. PMID:26057625

  19. Molecular quantum spintronics: supramolecular spin valves based on single-molecule magnets and carbon nanotubes.

    PubMed

    Urdampilleta, Matias; Nguyen, Ngoc-Viet; Cleuziou, Jean-Pierre; Klyatskaya, Svetlana; Ruben, Mario; Wernsdorfer, Wolfgang

    2011-01-01

    We built new hybrid devices consisting of chemical vapor deposition (CVD) grown carbon nanotube (CNT) transistors, decorated with TbPc(2) (Pc = phthalocyanine) rare-earth based single-molecule magnets (SMMs). The drafting was achieved by tailoring supramolecular π-π interactions between CNTs and SMMs. The magnetoresistance hysteresis loop measurements revealed steep steps, which we can relate to the magnetization reversal of individual SMMs. Indeed, we established that the electronic transport properties of these devices depend strongly on the relative magnetization orientations of the grafted SMMs. The SMMs are playing the role of localized spin polarizer and analyzer on the CNT electronic conducting channel. As a result, we measured magneto-resistance ratios up to several hundred percent. We used this spin valve effect to confirm the strong uniaxial anisotropy and the superparamagnetic blocking temperature (T(B) ~ 1 K) of isolated TbPc(2) SMMs. For the first time, the strength of exchange interaction between the different SMMs of the molecular spin valve geometry could be determined. Our results introduce a new design for operable molecular spintronic devices using the quantum effects of individual SMMs. PMID:22072910

  20. The effects of zeolite molecular sieve based surface treatments on the properties of wool fabrics

    NASA Astrophysics Data System (ADS)

    Carran, Richard S.; Ghosh, Arun; Dyer, Jolon M.

    2013-12-01

    Wool is a natural composite fiber, with keratin and keratin-associated proteins as the key molecular components. The outermost surface of wool fibers comprises a hydrophobic lipid layer that can lead to unsatisfactory processing and properties of fabric products. In this study, molecular sieve 5A, a Na+ and Ca2+ exchanged type A zeolite with a 1:1 Si:Al ratio was integrated onto the surface of wool using 3-mercaptopropyl trimethoxy silane. The resultant surface morphology, hydrophilicity and mechanical performance of the treated wool fabrics were then evaluated. Notably, the surface hydrophilicity of wool was observed to increase dramatically. When wool was treated with a dispersion of 2 wt% acetic acid, 2.5 wt% zeolite and 0.3 wt% or more silane, the water contact angle was observed to decrease from an average value of 148° to 0° over a period of approximately 30 s. Scanning electron microscopic imaging indicated good coverage of the wool surface with zeolite particles, with infrared spectroscopic evaluation indicating strong bonding of the dealuminated zeolite to wool keratins. This application of zeolite showed no adverse effects on the tensile and other mechanical properties of the fabric. This study indicates that zeolite-based treatment is a potentially efficient approach to increasing the surface hydrophilicity and modifying other key surface properties of wool and wool fabrics.

  1. Self-assembly of [3]catenanes and a [4]molecular necklace based on a cryptand/paraquat recognition motif.

    PubMed

    Ye, Yang; Wang, Shu-Ping; Zhu, Bin; Cook, Timothy R; Wu, Jing; Li, Shijun; Stang, Peter J

    2015-06-01

    Hierarchical self-assembly centered on metallacyclic scaffolds greatly facilitates the construction of mechanically interlocked structures. The formation of two [3]catenanes and one [4]molecular necklace is presented by utilizing the orthogonality of coordination-driven self-assembly and crown ether-based cryptand/paraquat derivative complexation. The threaded [3]catenanes and [4]molecular necklace were fabricated by using ten and nine total molecular components, respectively, from four and three unique species in solution, respectively. In all cases single supramolecular ensembles were obtained, attesting to the high degree of structural complexity made possible via self-assembly approaches. PMID:25996900

  2. Self-assembly of [3]catenanes and a [4]molecular necklace based on a cryptand/paraquat recognition motif.

    PubMed

    Ye, Yang; Wang, Shu-Ping; Zhu, Bin; Cook, Timothy R; Wu, Jing; Li, Shijun; Stang, Peter J

    2015-06-01

    Hierarchical self-assembly centered on metallacyclic scaffolds greatly facilitates the construction of mechanically interlocked structures. The formation of two [3]catenanes and one [4]molecular necklace is presented by utilizing the orthogonality of coordination-driven self-assembly and crown ether-based cryptand/paraquat derivative complexation. The threaded [3]catenanes and [4]molecular necklace were fabricated by using ten and nine total molecular components, respectively, from four and three unique species in solution, respectively. In all cases single supramolecular ensembles were obtained, attesting to the high degree of structural complexity made possible via self-assembly approaches.

  3. Isoindigo-based polymer photovoltaics: modifying polymer molecular structures to control the nanostructural packing motif.

    PubMed

    Kim, Yu Jin; Lee, Yun-Ji; Kim, Yun-Hi; Park, Chan Eon

    2016-07-21

    Donor molecular structures, and their packing aspects in donor:acceptor active blends, play a crucial role in the photovoltaic performance of polymer solar cells. We systematically investigated a series of isoindigo-based donor polymers within the framework of a three-dimensional (3D) crystalline motif by modifying their chemical structures, thereby affecting device performances. Although our isoindigo-based polymer series contained polymers that differed only by their alkyl side chains and/or donating units, they showed quite different nanoscale morphological properties, which resulted in significantly different device efficiencies. Notably, blends of our isoindigo-based donor polymer systems with an acceptor compound, whereby the blends had more intermixed network morphologies and stronger face-on orientations of the polymer crystallites, provided better-performing photovoltaic devices. This behavior was analyzed using atomic force microscopy (AFM) and two-dimensional grazing incidence wide angle X-ray diffraction (2D-GIWAXD). To the best of our knowledge, no correlation has been reported previously between 3D nano-structural donor crystallites and device performances, particularly for isoindigo-based polymer systems. PMID:27326694

  4. Isoindigo-based polymer photovoltaics: modifying polymer molecular structures to control the nanostructural packing motif.

    PubMed

    Kim, Yu Jin; Lee, Yun-Ji; Kim, Yun-Hi; Park, Chan Eon

    2016-07-21

    Donor molecular structures, and their packing aspects in donor:acceptor active blends, play a crucial role in the photovoltaic performance of polymer solar cells. We systematically investigated a series of isoindigo-based donor polymers within the framework of a three-dimensional (3D) crystalline motif by modifying their chemical structures, thereby affecting device performances. Although our isoindigo-based polymer series contained polymers that differed only by their alkyl side chains and/or donating units, they showed quite different nanoscale morphological properties, which resulted in significantly different device efficiencies. Notably, blends of our isoindigo-based donor polymer systems with an acceptor compound, whereby the blends had more intermixed network morphologies and stronger face-on orientations of the polymer crystallites, provided better-performing photovoltaic devices. This behavior was analyzed using atomic force microscopy (AFM) and two-dimensional grazing incidence wide angle X-ray diffraction (2D-GIWAXD). To the best of our knowledge, no correlation has been reported previously between 3D nano-structural donor crystallites and device performances, particularly for isoindigo-based polymer systems.

  5. Nickel complex with internal bases as efficient molecular catalyst for photochemical H2 production.

    PubMed

    Yang, Yong; Wang, Mei; Xue, Liqin; Zhang, Fengbo; Chen, Lin; Ahlquist, Mårten S G; Sun, Licheng

    2014-10-01

    A Ni complex with internal bases that contain bipyridine-derived ligands, [Ni(L)2 (H2 O)2 ](BF4 )2 ([1](BF4 )2 , L=2-(2-pyridyl)-1,8-naphthyridine), and a reference complex that bears analogous bipyridine-derived ligands but without an internal base, [Ni(L')3 ](BF4 )2 ([2](BF4 )2 , L'=2-(2-pyridyl)quinoline), were synthesized and characterized. The electrochemical properties of these complexes were studied in CH3 CN, H2 O, and a mixture of EtOH/H2 O. The fluorescence spectroscopic studies suggest that both dynamic and the sphere-of-action static quenching exist in the fluorescein Fl(2-) /[1](2+) and Fl(2-) /[2](2+) systems. These noble-metal-free molecular systems were studied for photocatalytic H2 generation. Under optimal conditions, the turnover number of H2 evolution reaches 3230 based on [1](2+) , whereas [2](2+) displays only approximately one third of the turnover of [1](2+) . A plausible mechanism for the catalytic H2 generation by [1](2+) is presented based on DFT calculations. PMID:25179906

  6. Electroanalysis of myoglobin based on electropolymerized molecularly imprinted polymer poly-o-phenylenediamine and carbon nanotubes/screen printed electrode.

    PubMed

    Shumyantseva, V V; Bulko, T V; Sigolaeva, L V; Kuzikov, A V; Archakov, A I

    2016-05-01

    Electroanalysis of myoglobin as a marker of acute myocardial infarction by means of screenprinted electrodes modified with multiwalled carbon nanotubes and polymeric artificial antibodies is developed. Plastic antibodies to myoglobin (molecularly imprinted polymers, MIPs) based on o-phenylenediamine were produced by electropolymerization. Molecular imprinting technology in biosensor analysis was used as alternative to natural receptors (namely, antibodies) and demonstrated high sensitivity (1.5 × 10(-2) A/nmol of myoglobin) and selectivity.

  7. Electroanalysis of myoglobin based on electropolymerized molecularly imprinted polymer poly-o-phenylenediamine and carbon nanotubes/screen printed electrode.

    PubMed

    Shumyantseva, V V; Bulko, T V; Sigolaeva, L V; Kuzikov, A V; Archakov, A I

    2016-05-01

    Electroanalysis of myoglobin as a marker of acute myocardial infarction by means of screenprinted electrodes modified with multiwalled carbon nanotubes and polymeric artificial antibodies is developed. Plastic antibodies to myoglobin (molecularly imprinted polymers, MIPs) based on o-phenylenediamine were produced by electropolymerization. Molecular imprinting technology in biosensor analysis was used as alternative to natural receptors (namely, antibodies) and demonstrated high sensitivity (1.5 × 10(-2) A/nmol of myoglobin) and selectivity. PMID:27417724

  8. Research Update: Comparison of salt- and molecular-based iodine treatments of PbS nanocrystal solids for solar cells

    SciTech Connect

    Jähnig, Fabian; Bozyigit, Deniz; Yarema, Olesya; Wood, Vanessa

    2015-02-01

    Molecular- and salt-based chemical treatments are believed to passivate electronic trap states in nanocrystal-based semiconductors, which are considered promising for solar cells but suffer from high carrier recombination. Here, we compare the chemical, optical, and electronic properties of PbS nanocrystal-based solids treated with molecular iodine and tetrabutylammonium iodide. Surprisingly, both treatments increase—rather than decrease—the number density of trap states; however, the increase does not directly influence solar cell performance. We explain the origins of the observed impact on solar cell performance and the potential in using different chemical treatments to tune charge carrier dynamics in nanocrystal-solids.

  9. Estimation of Linear Viscoelasticity of Polymer Melts in Molecular Dynamics Simulations Based on Relaxation Mode Analysis

    NASA Astrophysics Data System (ADS)

    Iwaoka, Nobuyuki; Hagita, Katsumi; Takano, Hiroshi

    2014-03-01

    On the basis of relaxation mode analysis (RMA), we present an efficient method to estimate the linear viscoelasticity of polymer melts in a molecular dynamics (MD) simulation. Slow relaxation phenomena appeared in polymer melts cause a problem that a calculation of the stress relaxation function in MD simulations, especially in the terminal time region, requires large computational efforts. Relaxation mode analysis is a method that systematically extracts slow relaxation modes and rates of the polymer chain from the time correlation of its conformations. We show the computational cost may be drastically reduced by combining a direct calculation of the stress relaxation function based on the Green-Kubo formula with the relaxation rates spectra estimated by RMA. N. I. acknowledges the Graduate School Doctoral Student Aid Program from Keio University.

  10. Molecular bases for the asynchronous activation of sodium and potassium channels required for nerve impulse generation.

    PubMed

    Lacroix, Jérôme J; Campos, Fabiana V; Frezza, Ludivine; Bezanilla, Francisco

    2013-08-21

    Most action potentials are produced by the sequential activation of voltage-gated sodium (Nav) and potassium (Kv) channels. This is mainly achieved by the rapid conformational rearrangement of voltage-sensor (VS) modules in Nav channels, with activation kinetics up to 6-fold faster than Shaker-type Kv channels. Here, using mutagenesis and gating current measurements, we show that a 3-fold acceleration of the VS kinetics in Nav versus Shaker Kv channels is produced by the hydrophilicity of two "speed-control" residues located in the S2 and S4 segments in Nav domains I-III. An additional 2-fold acceleration of the Nav VS kinetics is provided by the coexpression of the β1 subunit, ubiquitously found in mammal tissues. This study uncovers the molecular bases responsible for the differential activation of Nav versus Kv channels, a fundamental prerequisite for the genesis of action potentials.

  11. Spin-dependent Otto quantum heat engine based on a molecular substance

    NASA Astrophysics Data System (ADS)

    Hübner, Wolfgang; Lefkidis, Georgios; Dong, Chuanding; Chaudhuri, Debapriya; Chotorlishvili, Levan; Berakdar, Jamal

    2015-03-01

    We explore the potential of single molecules for thermodynamic cycles. To this end we propose two molecular heat engines based on the realistic Ni2 dimer: a quantum Otto engine and a modified quantum Otto engine for which laser-induced optical excitations substitute for one of the heat-exchange points. For reliable predictions and to inspect the role of spin and electronic correlations we perform fully correlated ab initio calculations of the electronic structure and the excited states. We analyze the efficiency and the word output of the derived engines and find an enhancement when the spin degree of freedom is included. We also use the von Neumann entropy to describe correlations and entanglement of the engines during the cycles. Furthermore, we link our results to previous results regarding an isobaric stroke and a magnetic quantum Diesel engine on the same substance.

  12. Base and salt 3D forms of Emeraldine II polymers by Car-Parrinello molecular dynamics

    NASA Astrophysics Data System (ADS)

    Cavazzoni, Carlo; Colle, Renato; Farchioni, Riccardo; Grosso, Giuseppe

    2005-07-01

    We have studied structural and electronic properties of the three-dimensional crystalline regions of Emeraldine II polymers, in the base (EB-II) and salt (ES-II) forms, by means of first principle Car-Parrinello molecular dynamics. We compare the geometrical structures of the polymer chains in the primitive cells of EB-II and ES-II, pointing out the structural effects due to the protonation with HCl of the iminic nitrogens in the EB-II chains, and the effect of the counterions between neighboring chains. We also analyze the HOMO electron density distribution, band structure and density of states of the resulting bipolaronic structure of ES-II, which is energetically stable and maintains semiconductor character.

  13. Asymptotic analysis of microtubule-based transport by multiple identical molecular motors.

    PubMed

    McKinley, Scott A; Athreya, Avanti; Fricks, John; Kramer, Peter R

    2012-07-21

    We describe a system of stochastic differential equations (SDEs) which model the interaction between processive molecular motors, such as kinesin and dynein, and the biomolecular cargo they tow as part of microtubule-based intracellular transport. We show that the classical experimental environment fits within a parameter regime which is qualitatively distinct from conditions one expects to find in living cells. Through an asymptotic analysis of our system of SDEs, we develop a means for applying in vitro observations of the nonlinear response by motors to forces induced on the attached cargo to make analytical predictions for two parameter regimes that have thus far eluded direct experimental observation: (1) highly viscous in vivo transport and (2) dynamics when multiple identical motors are attached to the cargo and microtubule.

  14. Rule-based Modeling and Simulation of Biochemical Systems with Molecular Finite Automata

    PubMed Central

    Yang, Jin; Meng, Xin; Hlavacek, William S.

    2011-01-01

    We propose a theoretical formalism, molecular finite automata (MFA), to describe individual proteins as rule-based computing machines. The MFA formalism provides a framework for modeling individual protein behaviors and systems-level dynamics via construction of programmable and executable machines. Models specified within this formalism explicitly represent the context-sensitive dynamics of individual proteins driven by external inputs and represent protein-protein interactions as synchronized machine reconfigurations. Both deterministic and stochastic simulations can be applied to quantitatively compute the dynamics of MFA models. We apply the MFA formalism to model and simulate a simple example of a signal transduction system that involves a MAP kinase cascade and a scaffold protein. PMID:21073243

  15. Titania-based molecularly imprinted polymer for sulfonic acid dyes prepared by sol-gel method.

    PubMed

    Li, Man; Li, Rong; Tan, Jin; Jiang, Zi-Tao

    2013-03-30

    A novel titania-based molecularly imprinted polymer (MIP) was synthesized through sol-gel process with sunset yellow (Sun) as template, without use of functional monomer. MIP was used as a solid-phase extraction material for the isolation and enrichment of sulfonic acid dyes in beverages. The results showed that MIP exhibited better selectivity, higher recovery and adsorption capacity for the sulfonic acid dyes compared to the non-imprinted polymer (NIP). MIP presented highest extraction selectivity to Sun when pH less than or equal to 3. The adsorption capacity was 485.9 mg g(-1), which was larger than that of NIP (384.7 mg g(-1)). The better clean-up ability demonstrated the capability of MIP for the isolation and enrichment of sulfonic acid dyes in complicated food samples. The mean recoveries for the sulfonic acid dyes on MIP were from 81.9% to 97.2% in spiked soft drink.

  16. Molecular dynamics-based virtual screening: accelerating the drug discovery process by high-performance computing.

    PubMed

    Ge, Hu; Wang, Yu; Li, Chanjuan; Chen, Nanhao; Xie, Yufang; Xu, Mengyan; He, Yingyan; Gu, Xinchun; Wu, Ruibo; Gu, Qiong; Zeng, Liang; Xu, Jun

    2013-10-28

    High-performance computing (HPC) has become a state strategic technology in a number of countries. One hypothesis is that HPC can accelerate biopharmaceutical innovation. Our experimental data demonstrate that HPC can significantly accelerate biopharmaceutical innovation by employing molecular dynamics-based virtual screening (MDVS). Without using HPC, MDVS for a 10K compound library with tens of nanoseconds of MD simulations requires years of computer time. In contrast, a state of the art HPC can be 600 times faster than an eight-core PC server is in screening a typical drug target (which contains about 40K atoms). Also, careful design of the GPU/CPU architecture can reduce the HPC costs. However, the communication cost of parallel computing is a bottleneck that acts as the main limit of further virtual screening improvements for drug innovations.

  17. Molecular recognition of arginine by supramolecular complexation with calixarene crown ether based on surface plasmon resonance.

    PubMed

    Chen, Hongxia; Gu, Limin; Yin, Yongmei; Koh, Kwangnak; Lee, Jaebeom

    2011-01-01

    Arginine plays an important role in cell division and the functioning of the immune system. We describe a novel method by which arginine can be identified using an artificial monolayer based on surface plasmon resonance (SPR). The affinity of arginine binding its recognition molecular was compared to that of lysine. In fabrication of an arginine sensing interface, a calix[4]crown ether monolayer was anchored onto a gold surface and then characterized by Fourier Transform infrared reflection absorption spectroscopy, atomic force microscopy, and cyclic voltammetry. The interaction between arginine and its host compound was investigated by SPR. The calix[4]crown ether was found to assemble as a monolayer on the gold surface. Recognition of calix[4]crown monolayer was assessed by the selective binding of arginine. Modification of the SPR chip with the calix[4]crown monolayer provides a reliable and simple experimental platform for investigation of arginine under aqueous conditions.

  18. Chemical control of photochromism and a multiresponsive molecular switch based on a diarylethene derivative containing naphthol.

    PubMed

    Liu, Wenju; Li, Ziyong; Hu, Fang; Yin, Jun; Yu, Guang-Ao; Liu, Sheng Hua

    2014-12-01

    A photochemically inactive diarylethene derivative with a naphthol group bridging through the imidazole unit (DIN) was synthesized to characterize a multifunctional switch. Upon stimulation by radiation (UV and visible light), the target diarylethene derivative DIN was not photochemically inactive but photo-active, it could be photo-converted into a keto compound. Moreover, the photochromic reaction of DIN was observed when it was stimulated by the addition of acid or methylation. Fluorescence quenching and the bathochromic effect occurred when DIN was stimulated by the addition of copper ions and a base, respectively. Its optical properties could be regulated by various chemical stimuli. Thus, it can potentially be utilized as a multiresponsive molecular switch. PMID:25341073

  19. Exploring polymorphism of benzene and naphthalene with free energy based enhanced molecular dynamics.

    PubMed

    Schneider, Elia; Vogt, Leslie; Tuckerman, Mark E

    2016-08-01

    Prediction and exploration of possible polymorphism in organic crystal compounds are of great importance for industries ranging from organic electronics to pharmaceuticals to high-energy materials. Here we apply our crystal structure prediction procedure and the enhanced molecular dynamics based sampling approach called the Crystal-Adiabatic Free Energy Dynamics (Crystal-AFED) method to benzene and naphthalene. Crystal-AFED allows the free energy landscape of structures to be explored efficiently at any desired temperature and pressure. For each system, we successfully predict the most stable crystal structures at atmospheric pressure and explore the relative Gibbs free energies of predicted polymorphs at high pressures. Using Crystal-AFED sampling, we find that mixed structures, which typically cannot be discovered by standard crystal structure prediction methods, are prevalent in the solid forms of these compounds at high pressure. PMID:27484375

  20. Sorption of carbamazepine from water by magnetic molecularly imprinted polymers based on chitosan-Fe₃O₄.

    PubMed

    Zhang, Ya-Lei; Zhang, Juan; Dai, Chao-Meng; Zhou, Xue-Fei; Liu, Shu-Guang

    2013-09-12

    A novel magnetic-molecularly imprinted polymer (MMIP) based on chitosan-Fe₃O₄ has been synthesized for fast separation of carbamazepine (CBZ) from water. During polymerization, the modified chitosan-Fe₃O₄ was used not only as supporter but also as functional monomer. The properties of obtained MMIP were characterized by scanning electron and transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectra, thermo-gravimetric analysis and so on. The sorption equilibrium data was well described by Freundlich isotherm model and the increase in the temperature generated an increase in the sorption amount, indicating endothermic nature of adsorption process. Sorption kinetics followed the pseudo-second-order model. The feasibility of selective sorption of CBZ from real water by the MMIP was analyzed by using spiked real water samples. The result showed that the sorption capacity of MMIP has no obvious decrease in different water samples whereas there was obvious decline in the sorption amount of the MNIP.

  1. Paramagnetic molecule induced strong antiferromagnetic exchange coupling on a magnetic tunnel junction based molecular spintronics device.

    PubMed

    Tyagi, Pawan; Baker, Collin; D'Angelo, Christopher

    2015-07-31

    This paper reports our Monte Carlo (MC) studies aiming to explain the experimentally observed paramagnetic molecule induced antiferromagnetic coupling between ferromagnetic (FM) electrodes. Recently developed magnetic tunnel junction based molecular spintronics devices (MTJMSDs) were prepared by chemically bonding the paramagnetic molecules between the FM electrodes along the tunnel junction's perimeter. These MTJMSDs exhibited molecule-induced strong antiferromagnetic coupling. We simulated the 3D atomic model analogous to the MTJMSD and studied the effect of molecule's magnetic couplings with the two FM electrodes. Simulations show that when a molecule established ferromagnetic coupling with one electrode and antiferromagnetic coupling with the other electrode, then theoretical results effectively explained the experimental findings. Our studies suggest that in order to align MTJMSDs' electrodes antiparallel to each other, the exchange coupling strength between a molecule and FM electrodes should be ∼50% of the interatomic exchange coupling for the FM electrodes.

  2. Capillary electrophoresis and fluorescence studies on molecular beacon-based variable length oligonucleotide target discrimination.

    PubMed

    Ramachandran, Akhilesh; Zhang, Minquan; Goad, David; Olah, Glenn; Malayer, Jerry R; El-Rassi, Ziad

    2003-01-01

    Molecular beacons (MBs) are oligonucleotide probes having a compact hairpin structure, with a fluorophore attached to one end and a quencher molecule attached to the other end. In its native state, the fluorophore is quenched by virtue of its proximity to the quencher molecule. Upon hybridization with its complementary oligonucleotide target, fluorescence is elicited due to a conformational change that results in separation of the fluorophore and quencher molecule. The present study describes the hybridization interaction of an MB to various complementary target sequences. The effects of temperature and length of complementary target sequences on hybridization were investigated using capillary electrophoresis and solution-based fluorescence techniques. Hybridization efficiency was dependent on the ability of the target sequences to destabilize the stem region by binding directly to the stem region. Optimal hybridization occurred between 40 and 50 degrees C for all targets tested, with the true target forming a more stable hybrid complex.

  3. Detection of trinitrotoluene based on SPR in molecularly imprinted polymer on plastic optical fiber

    NASA Astrophysics Data System (ADS)

    Cennamo, N.; Pesavento, M.; D'Agostino, G.; Galatus, R.; Bibbò, Luigi; Zeni, Luigi

    2013-05-01

    In this work an innovative and low cost optical chemical sensor, based on surface plasmon resonance in plastic optical fiber, is presented and experimentally tested for the detection and analysis of trinitrotoluene (TNT). The fabricated optical chemical sensor was realized removing the cladding of a plastic optical fiber along half the circumference, spin coating on the exposed core a buffer of Microposit S1813 photoresist, and finally sputtering a thin gold film. A Molecularly Imprinted Polymer (MIP) film was deposited on the thin gold film for the selective detection of TNT. It has been found that the sensor recognizes trinitrotoluene, since the SPR signal is affected by the presence of TNT in the polymer, while with a slow response kinetics, probably due to the thickness of the polymeric layer.

  4. Study on resist performance of chemically amplified molecular resist based on noria derivative and calixarene derivative

    NASA Astrophysics Data System (ADS)

    Yamamoto, Hiroki; Kudo, Hiroto; Kozawa, Takahiro

    2014-03-01

    Novel resist materials are required for lithographic processing with ionization radiation such as extreme ultraviolet (EUV) and electron beam (EB) exposure tool. In this study, we developed positive-tone chemically amplified molecular resists based on noria derivatives and calixarene derivatives and evaluated the lithographic performance using EUV and EB. We make clear that a small change in modification of noria resists can cause a significant change of sensitivity. Especially, it is useful for the improvement of resist sensitivities to use protecting groups such as 2-acetyloxy-2-methyladamantyl ester (AD) groups and ethoxy groups. Also, novel calixarene derivative such as pillar[5]arene protected by AD showed a semi-isolated pattern with the line width of 40 nm (pitch: 100nm). Noria derivatives and calixarene derivative resists were promising candidates because of high sensitivity, high resolution and etch durability similar to conventional resist such as ZEP 520A and UVIII.

  5. Synthesis and Bioconjugation of Gold Nanoparticles as Potential Molecular Probes for Light-Based Imaging Techniques

    PubMed Central

    Rayavarapu, Raja Gopal; Petersen, Wilma; Ungureanu, Constantin; Post, Janine N.; van Leeuwen, Ton G.; Manohar, Srirang

    2007-01-01

    We have synthesized and characterized gold nanoparticles (spheres and rods) with optical extinction bands within the “optical imaging window.” The intense plasmon resonant driven absorption and scattering peaks of these nanoparticles make them suitable as contrast agents for optical imaging techniques. Further, we have conjugated these gold nanoparticles to a mouse monoclonal antibody specific to HER2 overexpressing SKBR3 breast carcinoma cells. The bioconjugation protocol uses noncovalent modes of binding based on a combination of electrostatic and hydrophobic interactions of the antibody and the gold surface. We discuss various aspects of the synthesis and bioconjugation protocols and the characterization results of the functionalized nanoparticles. Some proposed applications of these potential molecular probes in the field of biomedical imaging are also discussed. PMID:18354723

  6. Molecular Simulations of Graphene-Based Electric Double-Layer Capacitors

    NASA Astrophysics Data System (ADS)

    Kalluri, Raja K.; Konatham, Deepthi; Striolo, Alberto

    2011-03-01

    Towards deploying renewable energy sources it is crucial to develop efficient and cost-effective technologies to store electricity. Traditional batteries are plagued by a number of practical problems that at present limit their widespread applicability. One possible solution is represented by electric double-layer capacitors (EDLCs). To deploy EDLCs at the large scale it is necessary to better understand how electrolytes pack and diffuse within narrow charged pores. We present here simulation results for the concentrated aqueous solutions of NaCl, CsCl, and NaI confined within charged graphene-based porous materials. We discuss how the structure of confined water, the salt concentration, the ions size, and the surface charge density determine the accumulation of electrolytes within the porous network. Our results, compared to data available for bulk systems, are critical for relating macroscopic observations to molecular-level properties of the confined working fluids. Research supported by the Department of Energy.

  7. XML-based approaches for the integration of heterogeneous bio-molecular data

    PubMed Central

    Mesiti, Marco; Jiménez-Ruiz, Ernesto; Sanz, Ismael; Berlanga-Llavori, Rafael; Perlasca, Paolo; Valentini, Giorgio; Manset, David

    2009-01-01

    Background The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. Results In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. Conclusion XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources. PMID:19828083

  8. Fragment-based drug discovery and molecular docking in drug design.

    PubMed

    Wang, Tao; Wu, Mian-Bin; Chen, Zheng-Jie; Chen, Hua; Lin, Jian-Ping; Yang, Li-Rong

    2015-01-01

    Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed. PMID:25420726

  9. Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation.

    PubMed

    Meduru, Harika; Wang, Yeng-Tseng; Tsai, Jeffrey J P; Chen, Yu-Ching

    2016-06-13

    Dipeptidyl peptidase-4 (DPP-4) is the vital enzyme that is responsible for inactivating intestinal peptides glucagon like peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), which stimulates a decline in blood glucose levels. The aim of this study was to explore the inhibition activity of small molecule inhibitors to DPP-4 following a computational strategy based on docking studies and molecular dynamics simulations. The thorough docking protocol we applied allowed us to derive good correlation parameters between the predicted binding affinities (pKi) of the DPP-4 inhibitors and the experimental activity values (pIC50). Based on molecular docking receptor-ligand interactions, pharmacophore generation was carried out in order to identify the binding modes of structurally diverse compounds in the receptor active site. Consideration of the permanence and flexibility of DPP-4 inhibitor complexes by means of molecular dynamics (MD) simulation specified that the inhibitors maintained the binding mode observed in the docking study. The present study helps generate new information for further structural optimization and can influence the development of new DPP-4 inhibitors discoveries in the treatment of type-2 diabetes.

  10. Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation

    PubMed Central

    Meduru, Harika; Wang, Yeng-Tseng; Tsai, Jeffrey J. P.; Chen, Yu-Ching

    2016-01-01

    Dipeptidyl peptidase-4 (DPP-4) is the vital enzyme that is responsible for inactivating intestinal peptides glucagon like peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), which stimulates a decline in blood glucose levels. The aim of this study was to explore the inhibition activity of small molecule inhibitors to DPP-4 following a computational strategy based on docking studies and molecular dynamics simulations. The thorough docking protocol we applied allowed us to derive good correlation parameters between the predicted binding affinities (pKi) of the DPP-4 inhibitors and the experimental activity values (pIC50). Based on molecular docking receptor-ligand interactions, pharmacophore generation was carried out in order to identify the binding modes of structurally diverse compounds in the receptor active site. Consideration of the permanence and flexibility of DPP-4 inhibitor complexes by means of molecular dynamics (MD) simulation specified that the inhibitors maintained the binding mode observed in the docking study. The present study helps generate new information for further structural optimization and can influence the development of new DPP-4 inhibitors discoveries in the treatment of type-2 diabetes. PMID:27304951

  11. Molecular Biomarker-Based Biokinetic Modeling of a PCE-Dechlorinating and Methanogenic Mixed Culture

    SciTech Connect

    Heavner, Gretchen L. W.; Rowe, Annette R.; Mansfeldt, Cresten B.; Pan, Ju Khuan; Gossett, James M.; Richardson, Ruth E.

    2013-04-16

    Bioremediation of chlorinated ethenes via anaerobic reductive dechlorination relies upon the activity of specific microbial population-most notably Dehalococcoides (DHC) strains. In the lab and field Dehalococcoides grow most robustly in mixed communities which usually contain both fermenters and methanogens. Recently, researchers have been developing quantitative molecular biomarkers to aid in field site diagnostics and it is hoped that these biomarkers could aid in the modeling of anaerobic reductive dechlorination. A comprehensive biokinetic model of a community containing Dehalococcoides mccartyi (formerly D. ethenogenes) was updated to describe continuously fed reactors with specific biomass levels based on quantitative PCR (qPCR)-based population data (DNA and RNA). The model was calibrated and validated with subsets of chemical and molecular biological data from various continuous feed experiments (n = 24) with different loading rates of the electron acceptor (1.5 to 482 μeeq/L-h), types of electron acceptor (PCE, TCE, cis-DCE) and electron donor to electron acceptor ratios. The resulting model predicted the sum of dechlorination products vinyl chloride (VC) and ethene (ETH) well. However, VC alone was under-predicted and ETH was over predicted. Consequently, competitive inhibition among chlorinated ethenes was examined and then added to the model. Additionally, as 16S rRNA gene copy numbers did not provide accurate model fits in all cases, we examined whether an improved fit could be obtained if mRNA levels for key functional enzymes could be used to infer respiration rates. The resulting empirically derived mRNA “adjustment factors” were added to the model for both DHC and the main methanogen in the culture (a Methanosaeta species) to provide a more nuanced prediction of activity. Results of this study suggest that at higher feeding rates competitive inhibition is important and mRNA provides a more accurate indicator of a population’s instantaneous

  12. Activatable molecular MRI nanoprobe for tumor cell imaging based on gadolinium oxide and iron oxide nanoparticle.

    PubMed

    Li, Jingjing; Wang, Shan; Wu, Chen; Dai, Yue; Hou, Pingfu; Han, Cuiping; Xu, Kai

    2016-12-15

    Activatable molecular MRI nanoprobe for intracellular GSH sensing was designed. As an alternative to "always on" nanoprobe, activatable imaging nanoprobes which are designed to amplify or boost imaging signals only in response to the targets have attracted more and more attention. In this paper, we designed a novel activatable molecular magnetic resonance imaging (MRI) nanoprobe for tumor cell recognization based on a MRI signal variation induced by the distance change between T1 and T2 contrast agents (CAs) in the presence of glutathione (GSH). To achieve this aim, carboxyl group functionalized iron oxide nanoparticles (Fe3O4 NPs) and polyethylene glycol-coated gadolinium oxide (PEG-Gd2O3) NPs as T2 and T1 MRI CA were connected by cystamine which contains a disulfide linkage. Transmission electron microscopic (TEM), X-ray photoelectron spectroscopy (XPS), energy dispersive spectrometer (EDS), fourier transform infrared spectroscopy (FT-IR), mass spectra and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) were introduced for their characterizations. The formation of Fe3O4-cystamine-Gd2O3 (Fe3O4-SS-Gd2O3) nanocomplex resulted in a quenched T1 signal due to the near proximity of PEG-Gd2O3 NPs to Fe3O4 NPs and a "light-up" T1 signal with the cleavage of disulfide bond in the presence of GSH. These results provide not only an easy way to realize MRI of tumor cells based on the overexpressed intracellular GSH level, but also a new insight for the design of activatable MRI nanoprobe. PMID:27501342

  13. Species delimitation of Chinese hop-hornbeams based on molecular and morphological evidence.

    PubMed

    Lu, Zhiqiang; Zhang, Dan; Liu, Siyu; Yang, Xiaoyue; Liu, Xue; Liu, Jianquan

    2016-07-01

    Species delimitation through which infers species boundaries is emerging as a major work in modern systematics. Hop-hornbeam species in Ostrya (Betulaceae) are well known for their hard and heavy woods. Five species were described in China and their interspecific delimitations remain unclear. In this study, we firstly explored their distributions in all recorded field sites distributed in China. We then selected 110 samples from 22 natural populations of five species from this genus and one type specimen of O. yunnanensis, for molecular barcoding analyses. We sequenced four chloroplast (cp) DNA fragments (trnH-psbA, trnL-trnF, rps16, and trnG) and the nuclear internal transcribed spacer (ITS) region for all samples. Sequence variations of Ostrya from four cpDNA fragments identified three groups that showed no correspondence to any morphological delimitation because of the incomplete lineage sorting and/or possible interspecific introgression in the history. However, phylogenetic analyses of ITS sequence variations discerned four species, O. japonica, O. rehderiana, O. trichocarpa, and O. multinervis while O. yunnanensis nested within O. multinervis. Morphological clustering also discerned four species and showed the complete consistency with molecular evidence. Moreover, our phylogenetic analyses-based ITS sequence variations suggested that O. trichocarpa comprised an isolated lineage different from the other Eurasian ones. Based on these results, hop-hornbeams in China should be treated as four separate species. Our results further highlight the importance of ITS sequence variations in delimitating and discerning the closely related species in plants. PMID:27547308

  14. A unified molecular picture of the surfaces of aqueous acid, base, and salt solutions

    SciTech Connect

    Mucha, M.; Frigato, Tomaso; Levering, Lori; Allen, Heather C.; Tobias, Douglas J.; Dang, Liem X.; Jungwirth, Pavel

    2005-04-28

    A unified view of the structure of the air/solution interface of simple aqueous electrolytes containing monovalent inorganic ions is developed using molecular dynamics simulations and vibrational sum frequency generation spectroscopy. In salt solutions and bases the positively charged ions, such as alkali cations, are repelled from the air/solution interface, while the anions, such as halides or hydroxide, exhibit a varying propensity for the surface, correlated primarily with the polarizability of the ion. As a result, there is a net depletion of ions from the interfacial layer as a whole, which is connected via the Gibbs adsorption equation to an increase in surface tension with respect to neat water. The behavior of acids, such as aqueous HCl or HBr, is different due to a significant propensity of hydronium cations for the air/solution interface. Therefore, both cations and anions exhibit enhanced concentrations at the surface and, consequently, these acids reduce the surface tension of water. The key to the qualitatively different surface behavior of aqueous salt solutions and bases on one side and acids on the other thus lies in the appreciable adsorption of hydronium cations at the air/solution interface with their “hydrophobic” oxygen side oriented towards the gas phase. The results of the molecular dynamics calculations are supported by surface selective non-linear vibrational spectroscopy, which reveals among other things that the hydronium cations are present at the air/solution interface. The propensity of inorganic ions for the air/solution interface has important implications for heterogeneous chemical processes, in particular for atmospheric chemistry.

  15. Validation of the taxon Ixodes aragaoi Fonseca (Acari: Ixodidae) based on morphological and molecular data.

    PubMed

    Onofrio, Valeria C; Ramirez, Diego G; Giovanni, Dalton N S; Marcili, Arlei; Mangold, Atilio J; Venzal, José M; Mendonça, Ronaldo Z; Labruna, Marcelo B; Barros-Battesti, Darci M

    2014-01-01

    The species Ixodes aragaoi Fonseca was described as Ixodes ricinus aragaoi, and later placed in synonymy with Ixodes affinis. However, this synonymy was rejected and the subspecies was elevated to species, and named as I. aragaoi. Some researchers did not consider the validity of I. aragaoi and maintained the synonymy proposed until 1998 when I. aragaoi was revalidated, and it was suggested that Ixodes pararicinus could be a synonym. The aim of this study was to confirm the taxonomic validity of I. aragaoi by means of redescription of adults and molecular analysis. Morphological studies were performed by optical and scanning electron microscopy; types of I. aragaoi were compared with those of I. pararicinus from Argentina, and also with material of I. pararicinus from Uruguay and I. affinis from the United States. Mitochondrial 16S rDNA sequences were obtained for determining phylogenetic relationships based on maximum parsimony. Morphological and molecular differences between I. aragaoi, I. pararicinus from Argentina, and I. affinis confirm the validity of the first each of these species. The morphological similarities of I. pararicinus from Uruguay with I. aragaoi, and the small distance of nucleotide sequences between them, confirm that the Uruguayan ticks are in fact I. aragaoi and expand the geographical distribution of this species. Based on the specimens of Ixodes examined in the present study, from the same locality of the types of I. ricinus rochensis in Uruguay, we agree with the synonymy of this subspecies with I. aragaoi as previously reported. Finally, our analyses indicate that both I. aragaoi and Ixodes fuscipes, another South American tick species, belong to the I. ricinus complex, currently composed of 19 species.  PMID:25283212

  16. Molecular Topology and Local Dynamics Govern the Viscosity of Imidazolium-Based Ionic Liquids.

    PubMed

    Zhang, Yong; Xue, Lianjie; Khabaz, Fardin; Doerfler, Rose; Quitevis, Edward L; Khare, Rajesh; Maginn, Edward J

    2015-11-25

    A series of branched ionic liquids (ILs) based on the 1-(iso-alkyl)-3-methylimidazolium cation from 1-(1-methylethyl)-3-methylimidazolium bistriflimide to 1-(5-methylhexyl)-3-methylimidazolium bistriflimide and linear ILs based on the 1-(n-alkyl)-3-methylimidazolium cation from 1-propyl-3-methylimidazolium bistriflimide to 1-heptyl-3-methylimidazolum bistriflimide were recently synthesized and their physicochemical properties characterized. For the ILs with the same number of carbons in the alkyl chain, the branched IL was found to have the same density but higher viscosity than the linear one. In addition, the branched IL 1-(2-methylpropyl)-3-methylimidazolium bistriflimide ([2mC3C1Im][NTf2]) was found to have an abnormally high viscosity. Motivated by these experimental observations, the same ILs were studied using molecular dynamics (MD) simulations in the current work. The viscosities of each IL were calculated using the equilibrium MD method at 400 K and the nonequilibrium MD method at 298 K. The results agree with the experimental trend. The ion pair (IP) lifetime, spatial distribution function, and associated potential of mean force, cation size and shape, and interaction energy components were calculated from MD simulations. A quantitative correlation between the liquid structure and the viscosity was observed. Analysis shows that the higher viscosities in the branched ILs are due to the relatively more stable packing between the cations and anions indicated by the lower minima in the potential of mean force (PMF) surface. The abnormal viscosity of [2mC3C1Im][NTf2] was found to be the result of the specific side chain length and molecular structure.

  17. Molecular biomarker-based biokinetic modeling of a PCE-dechlorinating and methanogenic mixed culture.

    PubMed

    Heavner, Gretchen L W; Rowe, Annette R; Mansfeldt, Cresten B; Pan, Ju Khuan; Gossett, James M; Richardson, Ruth E

    2013-04-16

    Bioremediation of chlorinated ethenes via anaerobic reductive dechlorination relies upon the activity of specific microbial populations--most notably Dehalococcoides (DHC) strains. In the lab and field Dehalococcoides grow most robustly in mixed communities which usually contain both fermenters and methanogens. Recently, researchers have been developing quantitative molecular biomarkers to aid in field site diagnostics and it is hoped that these biomarkers could aid in the modeling of anaerobic reductive dechlorination. A comprehensive biokinetic model of a community containing Dehalococcoides mccartyi (formerly D. ethenogenes) was updated to describe continuously fed reactors with specific biomass levels based on quantitative PCR (qPCR)-based population data (DNA and RNA). The model was calibrated and validated with subsets of chemical and molecular biological data from various continuous feed experiments (n = 24) with different loading rates of the electron acceptor (1.5 to 482 μeeq/L-h), types of electron acceptor (PCE, TCE, cis-DCE) and electron donor to electron acceptor ratios. The resulting model predicted the sum of dechlorination products vinyl chloride (VC) and ethene (ETH) well. However, VC alone was under-predicted and ETH was over predicted. Consequently, competitive inhibition among chlorinated ethenes was examined and then added to the model. Additionally, as 16S rRNA gene copy numbers did not provide accurate model fits in all cases, we examined whether an improved fit could be obtained if mRNA levels for key functional enzymes could be used to infer respiration rates. The resulting empirically derived mRNA "adjustment factors" were added to the model for both DHC and the main methanogen in the culture (a Methanosaeta species) to provide a more nuanced prediction of activity. Results of this study suggest that at higher feeding rates competitive inhibition is important and mRNA provides a more accurate indicator of a population's instantaneous

  18. A CELL-BASED MOLECULAR TRANSPORT SIMULATOR FOR PHARMACOKINETIC PREDICTION AND CHEMINFORMATIC EXPLORATION

    PubMed Central

    Zhang, Xinyuan; Shedden, Kerby; Rosania, Gus R.

    2009-01-01

    In the body, cell monolayers serve as permeability barriers, determining transport of drug molecules from one organ or tissue compartment to another. After oral administration, for example, drug transport across the epithelial cell monolayer lining the lumen of the intestine determines the fraction of drug in the gut that is absorbed by the body. By modeling passive transcellular transport properties in the presence of an apical to basolateral concentration gradient, we demonstrate how a computational, cell-based molecular transport simulator can be used to define a physicochemical property space occupied by molecules with desirable permeability and intracellular retention characteristics. Considering extracellular domains of cell surface receptors located on the opposite side of a cell monolayer as a drug’s desired site-of-action, simulation of transcellular transport can be used to define the physicochemical properties of molecules with maximal transcellular permeability but minimal intracellular retention. Arguably, these molecules would possess very desirable features: least likely to exhibit non-specific toxicity, metabolism and side effects associated with high (undesirable) intracellular accumulation; and, most likely to exhibit favorable bioavailability and efficacy associated with maximal rates of transport across cells and minimal intracellular retention, resulting in (desirable) accumulation at the extracellular site-of-action. Calculated permeability predictions showed good correlations with PAMPA, Caco2, and intestinal permeability measurements, without “training” the model and without resorting to statistical regression techniques to “fit” the data. Therefore, cell-based molecular transport simulators could be useful in silico screening tools for chemical genomics and drug discovery. PMID:17140258

  19. Molecular biomarker-based biokinetic modeling of a PCE-dechlorinating and methanogenic mixed culture.

    PubMed

    Heavner, Gretchen L W; Rowe, Annette R; Mansfeldt, Cresten B; Pan, Ju Khuan; Gossett, James M; Richardson, Ruth E

    2013-04-16

    Bioremediation of chlorinated ethenes via anaerobic reductive dechlorination relies upon the activity of specific microbial populations--most notably Dehalococcoides (DHC) strains. In the lab and field Dehalococcoides grow most robustly in mixed communities which usually contain both fermenters and methanogens. Recently, researchers have been developing quantitative molecular biomarkers to aid in field site diagnostics and it is hoped that these biomarkers could aid in the modeling of anaerobic reductive dechlorination. A comprehensive biokinetic model of a community containing Dehalococcoides mccartyi (formerly D. ethenogenes) was updated to describe continuously fed reactors with specific biomass levels based on quantitative PCR (qPCR)-based population data (DNA and RNA). The model was calibrated and validated with subsets of chemical and molecular biological data from various continuous feed experiments (n = 24) with different loading rates of the electron acceptor (1.5 to 482 μeeq/L-h), types of electron acceptor (PCE, TCE, cis-DCE) and electron donor to electron acceptor ratios. The resulting model predicted the sum of dechlorination products vinyl chloride (VC) and ethene (ETH) well. However, VC alone was under-predicted and ETH was over predicted. Consequently, competitive inhibition among chlorinated ethenes was examined and then added to the model. Additionally, as 16S rRNA gene copy numbers did not provide accurate model fits in all cases, we examined whether an improved fit could be obtained if mRNA levels for key functional enzymes could be used to infer respiration rates. The resulting empirically derived mRNA "adjustment factors" were added to the model for both DHC and the main methanogen in the culture (a Methanosaeta species) to provide a more nuanced prediction of activity. Results of this study suggest that at higher feeding rates competitive inhibition is important and mRNA provides a more accurate indicator of a population's instantaneous

  20. Competency-based education for the molecular genetic pathology fellow: a report of the association for molecular pathology training and education committee.

    PubMed

    Talbert, Michael L; Dunn, S Terence; Hunt, Jennifer; Hillyard, David R; Mirza, Imran; Nowak, Jan A; Van Deerlin, Vivianna; Vnencak-Jones, Cindy L

    2009-11-01

    The following report represents guidelines for competency-based fellowship training in Molecular Genetic Pathology (MGP) developed by the Association for Molecular Pathology Training and Education Committee and Directors of MGP Programs in the United States. The goals of the effort were to describe each of the Accreditation Council for Graduate Medical Education competencies as they apply to MGP fellowship training, provide a summary of goals and objectives, and recommend assessment tools. These guidelines are particularly pertinent to MGP training, which is a relatively new specialty that operates within a rapidly changing scientific and technological arena. It is hoped that this document will provide additional material for directors of existing MGP programs to consider for improvement of program objectives and enhancement of evaluation tools already in place. In addition, the guidelines should provide a valuable framework for the development of new MGP programs.