Science.gov

Sample records for bases moleculares del

  1. DNA based molecular motors

    NASA Astrophysics Data System (ADS)

    Michaelis, Jens; Muschielok, Adam; Andrecka, Joanna; Kügel, Wolfgang; Moffitt, Jeffrey R.

    2009-12-01

    Most of the essential cellular processes such as polymerisation reactions, gene expression and regulation are governed by mechanical processes. Controlled mechanical investigations of these processes are therefore required in order to take our understanding of molecular biology to the next level. Single-molecule manipulation and force spectroscopy have over the last 15 years been developed into extremely powerful techniques. Applying these techniques to the investigation of proteins and DNA molecules has led to a mechanistic understanding of protein function on the level of single molecules. As examples for DNA based molecular machines we will describe single-molecule experiments on RNA polymerases as well as on the packaging of DNA into a viral capsid-a process that is driven by one of the most powerful molecular motors.

  2. Polypeptides Based Molecular Electronics

    DTIC Science & Technology

    2008-10-06

    Molecular Electronics 4 Figure 3. Dehydration synthesis reaction CHAPTER 2 Review of Literature 2.1 Peptides 2.1.1 Introduction to peptides...Peptides are biomolecules formed from the 20 naturally occurring amino acids. Figure 3 shows dehydration synthesis reaction (known as condensation

  3. Nucleic acid based molecular devices.

    PubMed

    Krishnan, Yamuna; Simmel, Friedrich C

    2011-03-28

    In biology, nucleic acids are carriers of molecular information: DNA's base sequence stores and imparts genetic instructions, while RNA's sequence plays the role of a messenger and a regulator of gene expression. As biopolymers, nucleic acids also have exciting physicochemical properties, which can be rationally influenced by the base sequence in myriad ways. Consequently, in recent years nucleic acids have also become important building blocks for bottom-up nanotechnology: as molecules for the self-assembly of molecular nanostructures and also as a material for building machinelike nanodevices. In this Review we will cover the most important developments in this growing field of nucleic acid nanodevices. We also provide an overview of the biochemical and biophysical background of this field and the major "historical" influences that shaped its development. Particular emphasis is laid on DNA molecular motors, molecular robotics, molecular information processing, and applications of nucleic acid nanodevices in biology. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Rotaxane-based molecular muscles.

    PubMed

    Bruns, Carson J; Stoddart, J Fraser

    2014-07-15

    CONSPECTUS: More than two decades of investigating the chemistry of bistable mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, has led to the advent of numerous molecular switches that express controlled translational or circumrotational movement on the nanoscale. Directed motion at this scale is an essential feature of many biomolecular assemblies known as molecular machines, which carry out essential life-sustaining functions of the cell. It follows that the use of bistable MIMs as artificial molecular machines (AMMs) has been long anticipated. This objective is rarely achieved, however, because of challenges associated with coupling the directed motions of mechanical switches with other systems on which they can perform work. A natural source of inspiration for designing AMMs is muscle tissue, since it is a material that relies on the hierarchical organization of molecular machines (myosin) and filaments (actin) to produce the force and motion that underpin locomotion, circulation, digestion, and many other essential life processes in humans and other animals. Muscle is characterized at both microscopic and macroscopic length scales by its ability to generate forces that vary the distance between two points at the expense of chemical energy. Artificial muscles that mimic this ability are highly sought for applications involving the transduction of mechanical energy. Rotaxane-based molecular switches are excellent candidates for artificial muscles because their architectures intrinsically possess movable filamentous molecular components. In this Account, we describe (i) the different types of rotaxane "molecular muscle" architectures that express contractile and extensile motion, (ii) the molecular recognition motifs and corresponding stimuli that have been used to actuate them, and (iii) the progress made on integrating and scaling up these motions for potential applications. We identify three types of rotaxane muscles, namely, "daisy

  5. 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.

  6. 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.

  7. 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.

  8. 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

  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. Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

    PubMed Central

    2012-01-01

    Background While lenalidomide (LEN) shows high efficacy in myelodysplastic syndromes (MDS) with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. Design and methods We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by metaphase cytogenetics (MC) who underwent therapy with LEN. Results Fluorescence in situ hybridization (FISH) or single nucleotide polymorphism array (SNP-A)-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8%) additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08) and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11). However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Conclusions Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies. PMID:22390313

  12. 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).

  13. 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

  14. PaDEL-descriptor: an open source software to calculate molecular descriptors and fingerprints.

    PubMed

    Yap, Chun Wei

    2011-05-01

    PaDEL-Descriptor is a software for calculating molecular descriptors and fingerprints. The software currently calculates 797 descriptors (663 1D, 2D descriptors, and 134 3D descriptors) and 10 types of fingerprints. These descriptors and fingerprints are calculated mainly using The Chemistry Development Kit. Some additional descriptors and fingerprints were added, which include atom type electrotopological state descriptors, McGowan volume, molecular linear free energy relation descriptors, ring counts, count of chemical substructures identified by Laggner, and binary fingerprints and count of chemical substructures identified by Klekota and Roth. PaDEL-Descriptor was developed using the Java language and consists of a library component and an interface component. The library component allows it to be easily integrated into quantitative structure activity relationship software to provide the descriptor calculation feature while the interface component allows it to be used as a standalone software. The software uses a Master/Worker pattern to take advantage of the multiple CPU cores that are present in most modern computers to speed up calculations of molecular descriptors. The software has several advantages over existing standalone molecular descriptor calculation software. It is free and open source, has both graphical user interface and command line interfaces, can work on all major platforms (Windows, Linux, MacOS), supports more than 90 different molecular file formats, and is multithreaded. PaDEL-Descriptor is a useful addition to the currently available molecular descriptor calculation software. The software can be downloaded at http://padel.nus.edu.sg/software/padeldescriptor. Copyright © 2010 Wiley Periodicals, Inc.

  15. Bioassays Based on Molecular Nanomechanics

    DOE PAGES

    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

  16. 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. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Graphene-based nanoprobes for molecular diagnostics.

    PubMed

    Chen, Shixing; Li, Fuwu; Fan, Chunhai; Song, Shiping

    2015-10-07

    In recent years, graphene has received widespread attention owing to its extraordinary electrical, chemical, optical, mechanical and structural properties. Lately, considerable interest has been focused on exploring the potential applications of graphene in life sciences, particularly in disease-related molecular diagnostics. In particular, the coupling of functional molecules with graphene as a nanoprobe offers an excellent platform to realize the detection of biomarkers, such as nucleic acids, proteins and other bioactive molecules, with high performance. This article reviews emerging graphene-based nanoprobes in electrical, optical and other assay methods and their application in various strategies of molecular diagnostics. In particular, this review focuses on the construction of graphene-based nanoprobes and their special advantages for the detection of various bioactive molecules. Properties of graphene-based materials and their functionalization are also comprehensively discussed in view of the development of nanoprobes. Finally, future challenges and perspectives of graphene-based nanoprobes are discussed.

  18. Molecular profiling of neurons based on connectivity.

    PubMed

    Ekstrand, Mats I; Nectow, Alexander R; Knight, Zachary A; Latcha, Kaamashri N; Pomeranz, Lisa E; Friedman, Jeffrey M

    2014-05-22

    The complexity and cellular heterogeneity of neural circuitry presents a major challenge to understanding the role of discrete neural populations in controlling behavior. While neuroanatomical methods enable high-resolution mapping of neural circuitry, these approaches do not allow systematic molecular profiling of neurons based on their connectivity. Here, we report the development of an approach for molecularly profiling projective neurons. We show that ribosomes can be tagged with a camelid nanobody raised against GFP and that this system can be engineered to selectively capture translating mRNAs from neurons retrogradely labeled with GFP. Using this system, we profiled neurons projecting to the nucleus accumbens. We then used an AAV to selectively profile midbrain dopamine neurons projecting to the nucleus accumbens. By comparing the captured mRNAs from each experiment, we identified a number of markers specific to VTA dopaminergic projection neurons. The current method provides a means for profiling neurons based on their projections.

  19. 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

  20. An InDel-based linkage map of hot pepper (Capsicum annuum).

    PubMed

    Li, Weipeng; Cheng, Jiaowen; Wu, Zhiming; Qin, Cheng; Tan, Shu; Tang, Xin; Cui, Junjie; Zhang, Li; Hu, Kailin

    Two independent pepper (Capsicum annuum) genomes were published recently, opening a new era of molecular genetics research on pepper. However, pepper molecular marker technologies are still mainly focusing on the simple sequence repeats derived from public database or genomic library. The development and application of the third generation marker system such as single nucleotide polymorphisms, structure variations as well as insertion/deletion polymorphisms (InDels) is still in its infancy. In the present study, we developed InDel markers for pepper genetic mapping with the convenience of two whole-genome re-sequenced inbred lines BA3 (C. annuum) and B702 (C. annuum). A total of 154,519 and 149,755 InDel (1-5 bp) sites were identified for BA3 and B702, respectively, by the alignment of re-sequencing reads to Zunla-1 reference genome. Then, 14,498 InDel sites (only 4 and 5 bp) that are different between BA3 and B702 were predicted. Finally, within a random set of 1,000 primer pairs, 251 InDel markers were validated and mapped onto a linkage map using F2 population derived from the intraspecific cross BA3 × B702. The first InDel-based map, named as BB-InDel map, consisted of 12 linkage groups, covered a genetic distance of 1,178.01 cM and the average distance between bin markers was 5.01 cM. Compared to the Zunla-1 reference physical map, high consistency was observed on all 12 chromosomes, and the total length of scaffold anchored and physical distance covered by this map was 299.66 and 2,558.68 Mb, respectively, which accounted for 8.95 and 76.38 % of the Zunla-1 reference genome (3.35 Gb), respectively. Furthermore, 37 scaffolds (total length of 36.21 Mb) from the pseudo-chromosome (P0) of the current genome assembly were newly assigned to the corresponding chromosomes by 40 InDel markers. Thus, this map provided good genome coverage and would be useful for basic and applied research in pepper.

  1. Molecular-Based Devices and Circuits

    DTIC Science & Technology

    2008-09-23

    nano-cavities (50nm x 50nm) etched into the Si3N4 layer at the center of the electrode. Subsequently, molecules are self - assembled onto the bottom...various types of self assembled monolayers (SAMs) arranged in vertical configuration (Fig 2) . Each floor consists of different type of molecular layer...modified ferrocene film (Figure 2 compound 1) , and a the protein Azurin (Az). The Fc-based SAM can be used as a candidate for the bottom layer as we have

  2. Organic-based molecular switches for molecular electronics.

    PubMed

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

    2011-10-05

    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.

  3. Pre-Columbian tuberculosis in Tierra del Fuego? Discussion of the paleopathological and molecular evidence.

    PubMed

    Guichón, Ricardo A; Buikstra, Jane E; Stone, Anne C; Harkins, Kelly M; Suby, Jorge A; Massone, Mauricio; Prieto Lglesias, Alfredo; Wilbur, Alicia; Constantinescu, Florence; Rodríguez Martín, Conrado

    2015-12-01

    This work contributes to ongoing discussions about the nature of tuberculosis in the Western Hemisphere prior to the time of European contact. Our example, from the extreme south of South America was, at the time of our study, without firm temporal association or molecular characterization. In Tierra del Fuego, Constantinescu (1999) briefly described vertebral bone lesions compatible with TB in an undated skeleton from Myren 1 site (Chile). The remains of Myren are estimated to represent a man between 18 and 23 years old at the time of death. The objectives of this research are to extend this description, to present molecular results, to establish a radiocarbon date, and to report stable isotopic values for the remains. We provide further description of the remains, including tuberculosis-like skeletal pathology. Radiocarbon dating of 640±20 years BP attributes this individual to the precontact fourteenth-fifteenth centuries. Isotopic ratios for nitrogen and carbon from bone collagen suggest a mixed diet. Molecular results were positive for the rpoB quantitative PCR (qPCR) assays but negative for two independent IS6110 and IS1081 qPCR assays. Further testing using genomic methods to target any mycobacteria for specific identification are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. [Aging and neurodegeneration: molecular and cellular bases].

    PubMed

    Peinado, M A; del Moral, M L; Esteban, F J; Martínez-Lara, E; Siles, E; Jiménez, A; Hernández-Cobo, R; Blanco, S; Rodrigo, J; Pedrosa, J A

    A review about the possible cellular and molecular mechanisms of aging and related neurodegenerative diseases. The mechanisms involved in neuronal decrease, connectivity losses and glial reactivity, detected both in neurodegenerative (Alzheimer's disease) and physiological aging, are analyzed from the morphological and histological point of view to provide the morphofunctional base of the cognitive and intellectual alterations characterizing the senescence process. Taken together, these data are correlated to the possible genetical aspects implied in this process, reviewing the most relevant results on senescence and cellular death obtained from yeast, fruit fly and nematodes; besides this, a brief review of the molecular biology of gerontogenes was carried out, and the possible mechanisms inducing aging and neurodegenerative processes are analyzed according to the state-of-the-art related theories. Finally, cellular, biochemical and genetical data are correlated in the signal transduction way implied in the increase of the intracellular calcium level as the starting point of cell death. The main process implied in the neuronal cell death responsible for aging and the related neurodegenerative diseases are started by different agents such as the lacking of neurotrophic factors, hypoxia, hypoglycemia, excitotoxicity, and oxygen and nitrogen free radicals.

  5. 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

  6. Multicolor Electrochromic Devices Based on Molecular Plasmonics.

    PubMed

    Stec, Grant J; Lauchner, Adam; Cui, Yao; Nordlander, Peter; Halas, Naomi J

    2017-03-28

    Polycyclic aromatic hydrocarbon (PAH) molecules, the hydrogen-terminated, sub-nanometer-scale version of graphene, support plasmon resonances with the addition or removal of a single electron. Typically colorless when neutral, they are transformed into vivid optical absorbers in either their positively or negatively charged states. Here, we demonstrate a low-voltage, multistate electrochromic device based on PAH plasmon resonances that can be reversibly switched between nearly colorless (0 V), olive (+4 V), and royal blue (-3.5 V). The device exhibits highly efficient color change compared to electrochromic polymers and metal oxides, lower power consumption than liquid crystals, and is shown to reversibly switch for at least 100 cycles. We also demonstrate the additive property of molecular plasmon resonances in a single-layer device to display a reversible, transmissive-to-black device. This work illuminates the potential of PAH molecular plasmonics for the development of color displays and large-area color-changing applications due to their processability and ultralow power consumption.

  7. Clinical features and molecular bases of neuroacanthocytosis.

    PubMed

    Rampoldi, Luca; Danek, Adrian; Monaco, Anthony P

    2002-08-01

    The term acanthocytosis is derived from the Greek for "thorn" and is used to describe a peculiar spiky appearance of erythrocytes. Acanthocytosis is found to be associated with at least three hereditary neurological disorders that are generally referred to as neuroacanthocytosis. Abetalipoproteinaemia is an autosomal recessive condition, characterised by absence of serum apolipoprotein B containing lipoproteins leading to fat intolerance and fat-soluble vitamin deficiency. This results in a progressive spinocerebellar ataxia with peripheral neuropathy and retinitis pigmentosa. Chorea-acanthocytosis is also an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysphagia, dysarthria, areflexia, seizures and dementia. Some of its features, including choreic movements, peripheral neuropathy with areflexia, elevated serum creatine kinase levels and myopathy are shared by another form of neuroacanthocytosis, McLeod syndrome. Patients affected by this X-linked disorder also show abnormal expression of Kell blood group antigens and a permanent haemolytic state. In addition to these cases, acanthocytosis is occasionally associated with other neurological disorders, such as Hallervorden-Spatz disease. For each of the neuroacanthocytosis syndromes we review the main clinical features and their molecular bases. The recent molecular genetics findings are the first step towards the understanding of the pathogenetic mechanisms and eventually the search for effective treatments.

  8. Molecular Survey of Hepatitis C Virus in the Touristic City of Mar Del Plata, Argentina

    PubMed Central

    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

  9. PET-based molecular imaging in neuroscience.

    PubMed

    Jacobs, A H; Li, H; Winkeler, A; Hilker, R; Knoess, C; Rüger, A; Galldiks, N; Schaller, B; Sobesky, J; Kracht, L; Monfared, P; Klein, M; Vollmar, S; Bauer, B; Wagner, R; Graf, R; Wienhard, K; Herholz, K; Heiss, W D

    2003-07-01

    Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

  10. Molecular epidemiology and genetic diversity of hepatitis B virus in Mar del Plata city, Argentina.

    PubMed

    Barbini, Luciana; Elizalde, Mercedes; Torres, Carolina; Campos, Rodolfo

    2013-10-01

    The aim of this work was to describe the current molecular epidemiology and genetic diversity of HBV in Mar del Plata, an important Argentinean touristic city. The phylogenetic analysis of 29 HBV DNA positive serum samples showed that F1b was the predominant subgenotype (sgt, 62.1%), followed by sgt A2 (13.8%) and sgt F4, gt D and gt G (6.9% each). Among anti-HBc IgM positive samples, 75.0% were sgt F1b, followed by sgt F4 (12.5%), sgt A2 (6.25%) and sgt D (6.25%). Three recombinant full length genomes were found: two G/F1b (some of the first gt G detected in Argentina) and one F4/D2. The circulation of clinical important mutations in the city was described. Mutations at the HBsAg were detected in 34.5% of the analyzed samples, associated with laboratory diagnosis and antiviral treatment failures, immune escape and hepatocellular carcinoma. Most of the samples presented wild type BCP/PC sequences. Coalescence analysis for the most prevalent sgt F1b estimated that the diversification mainly occured during mid '90s and the tMRCA was estimated in 1987. Finally, the high presence of the autochthonous sgt F1b, associated with the anti-HBc IgM positive infection and its present-day diversification process, shows the strong impact of internal human migratory movements into the current population of Mar del Plata. Copyright © 2013 Elsevier B.V. All rights reserved.

  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. Logic circuits based on molecular spider systems.

    PubMed

    Mo, Dandan; Lakin, Matthew R; Stefanovic, Darko

    2016-08-01

    Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity.

  13. Molecular and Clinical Based Cardiovascular Care Program

    DTIC Science & Technology

    2007-01-01

    pathogenesis of coronary artery, peripheral vascular , and cerebrovascular disease . Impairment of endothelial function has been demonstrated after high...cardio’Va~ ct•b.r disease , Subsequently, ultrnlow-fat diets (:;;1.0% of totlll caloric intake as fat), emphasi?.in,g the amount ra.thcr th<•.o the...cardiovascular disease at the molecular disease stage and identify biomarkers predictive of sub- clinical CVD; and 3) Relate genomic/proteomic changes to the

  14. Quantitative molecular thermochemistry based on path integrals.

    PubMed

    Glaesemann, Kurt R; Fried, Laurence E

    2005-07-15

    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 for going beyond the harmonic analysis and to calculate the vibrational and rotational contributions to ab initio energies. This is an application and an extension of a method previously developed in our group [J. Chem. Phys. 118, 1596 (2003)].

  15. 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.

  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. Unidirectional light-driven molecular motors based on overcrowded alkenes.

    PubMed

    Cnossen, Arjen; Browne, Wesley R; Feringa, Ben L

    2014-01-01

    Over the last two decades, interest in nanotechnology has led to the design and synthesis of a toolbox of nanoscale versions of macroscopic devices and components. In molecular nanotechnology, linear motors based on rotaxanes and rotary motors based on overcrowded alkenes are particularly promising for performing work at the nanoscale. In this chapter, progress on light-driven molecular motors based on overcrowded alkenes is reviewed. Both the so-called first and second generation molecular motors are discussed, as well as their potential applications.

  18. Antibody-controlled actuation of DNA-based molecular circuits

    NASA Astrophysics Data System (ADS)

    Engelen, Wouter; Meijer, Lenny H. H.; Somers, Bram; de Greef, Tom F. A.; Merkx, Maarten

    2017-02-01

    DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically. Detailed characterization of the ATSE reaction allowed the establishment of a comprehensive model that describes the kinetics and thermodynamics of ATSE as a function of toehold length, antibody-epitope affinity and concentration. ATSE enables the introduction of complex signal processing in antibody-based diagnostics, as demonstrated here by constructing molecular circuits for multiplex antibody detection, integration of multiple antibody inputs using logic gates and actuation of enzymes and DNAzymes for signal amplification.

  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. Copyright © 2012 by Annual Reviews. All rights reserved.

  20. Molecular bases of methamphetamine-induced neurodegeneration.

    PubMed

    Cadet, Jean Lud; Krasnova, Irina N

    2009-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant drug, whose abuse has reached epidemic proportions worldwide. The addiction to METH is a major public concern because its chronic abuse is associated with serious health complications including deficits in attention, memory, and executive functions in humans. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. Thus, the purpose of the present paper is to review cellular and molecular mechanisms that might be responsible for METH neurotoxicity. These include oxidative stress, activation of transcription factors, DNA damage, excitotoxicity, blood-brain barrier breakdown, microglial activation, and various apoptotic pathways. Several approaches that allow protection against METH-induced neurotoxic effects are also discussed. Better understanding of the cellular and molecular mechanisms involved in METH toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of psychostimulant use disorders in humans.

  1. Development of molecular resists based on Phenyl[4]calixarene derivatives.

    NASA Astrophysics Data System (ADS)

    Echigo, Masatoshi; Hayashi, Hiromi; Oizumi, Hiroaki; Matsumaro, Kazuyuki; Itani, Toshiro

    2010-04-01

    We have developed negative-tone molecular resist based on C-4-cyclohexylphenylcalix[4]resorcinarene(MGR108) and positive-tone molecular resist based on protected C-4-isopropylphenylcalix[4]resorcinarene (MGR104P). Both MGR108 and MGR104P showed high solubility in both conventional resist solvents such as propylene glycol monomethyl ether and conventional alkaline developer of 0.26N TMAHaq. In this paper, we show current performance of resists by EB lithography (EBL) and EUV lithography (EUVL).

  2. Controlling charge current through a DNA based molecular transistor

    NASA Astrophysics Data System (ADS)

    Behnia, S.; Fathizadeh, S.; Ziaei, J.

    2017-01-01

    Molecular electronics is complementary to silicon-based electronics and may induce electronic functions which are difficult to obtain with conventional technology. We have considered a DNA based molecular transistor and study its transport properties. The appropriate DNA sequence as a central chain in molecular transistor and the functional interval for applied voltages is obtained. I-V characteristic diagram shows the rectifier behavior as well as the negative differential resistance phenomenon of DNA transistor. We have observed the nearly periodic behavior in the current flowing through DNA. It is reported that there is a critical gate voltage for each applied bias which above it, the electrical current is always positive.

  3. The molecular bases of the suicidal brain

    PubMed Central

    Turecki, Gustavo

    2017-01-01

    Suicide ranks among the leading causes of death around the world, and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors — such as familial and genetic predisposition, as well as early-life adversity — increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors associate with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes associated with suicidality, and presents some promising avenues for future research. PMID:25354482

  4. Ab initio Path Integral Molecular Dynamics Based on Fragment Molecular Orbital Method

    NASA Astrophysics Data System (ADS)

    Fujita, Takatoshi; Watanabe, Hirofumi; Tanaka, Shigenori

    2009-10-01

    We have developed an ab initio path integral molecular dynamics method based on the fragment molecular orbital method. This “FMO-PIMD” method can treat both nuclei and electrons quantum mechanically, and is useful to simulate large hydrogen-bonded systems with high accuracy. After a benchmark calculation for water monomer, water trimer and glycine pentamer have been studied using the FMO-PIMD method to investigate nuclear quantum effects on structure and molecular interactions. The applicability of the present approach is demonstrated through a number of test calculations.

  5. 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…

  6. 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…

  7. Optimal separable bases and molecular collisions

    SciTech Connect

    Poirier, Lionel 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 + H2 → H2 + 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.

  8. Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis*,**

    PubMed Central

    Marson, Fernando Augusto de Lima; Bertuzzo, Carmen Silvia; Ribeiro, Maria Ângela Gonçalves de Oliveira; Ribeiro, Antônio Fernando; Ribeiro, José Dirceu

    2013-01-01

    OBJECTIVE: To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. METHODS: We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. RESULTS: Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. CONCLUSIONS: The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset. PMID:23857699

  9. Possibility of gas sensor based on C20 molecular devices

    NASA Astrophysics Data System (ADS)

    Zhao, Wenkai; Yang, Chuanlu; Zou, Dongqing; Sun, Zhaopeng; Ji, Guomin

    2017-06-01

    We theoretically investigate the possibility of diatomic gas detection (NO, CO, O2) by making use of the transport properties of the C20 molecular junctions. The calculations are performed by using nonequilibrium Green's function (NEGF) formalism in combination with density functional theory (DFT). In this work, we systematically study the most stable adsorption structural configurations, adsorption energy, and the transport properties on C20 molecular junctions with these diatomic gas molecules. It is found that NO and O2 gas molecule can be detected selectively. We suggest its possibility of nanosensors for highly sensitive and selective based on C20 molecular junction systems.

  10. 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.

  11. Progress in molecular-based management of differentiated thyroid cancer

    PubMed Central

    Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin

    2014-01-01

    Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556

  12. A clinically applicable molecular-based classification for endometrial cancers.

    PubMed

    Talhouk, A; McConechy, M K; Leung, S; Li-Chang, H H; Kwon, J S; Melnyk, N; Yang, W; Senz, J; Boyd, N; Karnezis, A N; Huntsman, D G; Gilks, C B; McAlpine, J N

    2015-07-14

    Classification of endometrial carcinomas (ECs) by morphologic features is inconsistent, and yields limited prognostic and predictive information. A new system for classification based on the molecular categories identified in The Cancer Genome Atlas is proposed. Genomic data from the Cancer Genome Atlas (TCGA) support classification of endometrial carcinomas into four prognostically significant subgroups; we used the TCGA data set to develop surrogate assays that could replicate the TCGA classification, but without the need for the labor-intensive and cost-prohibitive genomic methodology. Combinations of the most relevant assays were carried forward and tested on a new independent cohort of 152 endometrial carcinoma cases, and molecular vs clinical risk group stratification was compared. Replication of TCGA survival curves was achieved with statistical significance using multiple different molecular classification models (16 total tested). Internal validation supported carrying forward a classifier based on the following components: mismatch repair protein immunohistochemistry, POLE mutational analysis and p53 immunohistochemistry as a surrogate for 'copy-number' status. The proposed molecular classifier was associated with clinical outcomes, as was stage, grade, lymph-vascular space invasion, nodal involvement and adjuvant treatment. In multivariable analysis both molecular classification and clinical risk groups were associated with outcomes, but differed greatly in composition of cases within each category, with half of POLE and mismatch repair loss subgroups residing within the clinically defined 'high-risk' group. Combining the molecular classifier with clinicopathologic features or risk groups provided the highest C-index for discrimination of outcome survival curves. Molecular classification of ECs can be achieved using clinically applicable methods on formalin-fixed paraffin-embedded samples, and provides independent prognostic information beyond

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Histological skin morphology enhancement base on molecular hyperspectral imaging technology.

    PubMed

    Li, Q; Sun, Z; Wang, Y; Liu, H; Guo, F; Zhu, J

    2014-08-01

    Most traditional skin histological analysis methods are based on the light microscopy images, which can only provide limited information and low contrast results for pathology evaluation. Molecular hyperspectral imaging technology can provide both spatial and spectral information of skin sections, which is a new method for histological skin analysis. The molecular hyperspectral imaging system was developed by coupling an acousto-optic tunable filters adapter to microscopy and the molecular hyperspectral images were analyzed by home-written software with image processing algorithms. Then, the histological structures in skin sections were investigated in several locations to evaluate the potential application of the molecular hyperspectral imaging technique to dermatology. Molecular hyperspectral images of skin sections were obtained. Single-band images, false color images, virtual 3D surface view images, and color-coded spectral clustering results were produced to highlight the skin structures for histological evaluation. Unlike traditional histological analysis with light microscopy, the molecular hyperspectral imaging technology can enhance the visualization of skin structures using their spectral signatures and their gray values. This technology has potential for the diagnosis and histopathologic characterization of different kind of skin cells. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. High molecular weight polyglycerol-based multivalent mannose conjugates.

    PubMed

    Kizhakkedathu, Jayachandran N; Creagh, A Louise; Shenoi, Rajesh A; Rossi, Nicholas A A; Brooks, Donald E; Chan, Timmy; Lam, Jonathan; Dandepally, Srinivasa R; Haynes, Charles A

    2010-10-11

    We report the synthesis and characterization of multivalent mannose conjugates based on high molecular weight hyperbranched polyglycerols (HPG). A range of glycoconjugates were synthesized from high molecular weight HPGs (up to 493 kDa) and varying mannose units (22-303 per HPG). Hemagglutination assays using fresh human red blood cells and concanavalin A (Con A) showed that HPG-mannose conjugates exhibited a large enhancement in the relative potency of conjugates (as high as 40000) along with a significant increment in relative activity per sugar (up to 255). The size of the HPG scaffold and the number of mannose residues per HPG were all shown to influence the enhancement of binding interactions with Con A. Isothermal titration calorimetry (ITC) experiments confirmed the enhanced binding affinity and showed that both molecular size and ligand density play important roles. The enhancement in Con A binding to the high molecular weight HPG-mannose conjugates is due to a combination of inter- and intramolecular mannose binding. A few fold increments in the binding constant were obtained over mannose upon covalent attachment to HPG. The binding enhancement is due to the highly favorable entropic contribution to the multiple interactions of Con A to mannose residues on HPG. The high molecular weight HPG-mannose conjugates showed positive cooperativity in binding to Con A. Although carbohydrate density has less of an effect on functional valency of the conjugate compared to the molecular size, it determines the binding affinity.

  19. 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…

  20. Antibody-controlled actuation of DNA-based molecular circuits

    PubMed Central

    Engelen, Wouter; Meijer, Lenny H. H.; Somers, Bram; de Greef, Tom F. A.; Merkx, Maarten

    2017-01-01

    DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically. Detailed characterization of the ATSE reaction allowed the establishment of a comprehensive model that describes the kinetics and thermodynamics of ATSE as a function of toehold length, antibody–epitope affinity and concentration. ATSE enables the introduction of complex signal processing in antibody-based diagnostics, as demonstrated here by constructing molecular circuits for multiplex antibody detection, integration of multiple antibody inputs using logic gates and actuation of enzymes and DNAzymes for signal amplification. PMID:28211541

  1. 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…

  2. 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…

  3. 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…

  4. A molecular diffusion based utility model for Drosophila larval phototaxis.

    PubMed

    Gong, Zhejun; Gong, Zhefeng

    2012-02-02

    Generally, utility based decision making models focus on experimental outcomes. In this paper we propose a utility model based on molecular diffusion to simulate the choice behavior of Drosophila larvae exposed to different light conditions. In this paper, light/dark choice-based Drosophila larval phototaxis is analyzed with our molecular diffusion based model. An ISCEM algorithm is developed to estimate the model parameters. By applying this behavioral utility model to light intensity and phototaxis data, we show that this model fits the experimental data very well. Our model provides new insights into decision making mechanisms in general. From an engineering viewpoint, we propose that the model could be applied to a wider range of decision making practices.

  5. A molecular diffusion based utility model for Drosophila larval phototaxis

    PubMed Central

    2012-01-01

    Background Generally, utility based decision making models focus on experimental outcomes. In this paper we propose a utility model based on molecular diffusion to simulate the choice behavior of Drosophila larvae exposed to different light conditions. Methods In this paper, light/dark choice-based Drosophila larval phototaxis is analyzed with our molecular diffusion based model. An ISCEM algorithm is developed to estimate the model parameters. Results By applying this behavioral utility model to light intensity and phototaxis data, we show that this model fits the experimental data very well. Conclusions Our model provides new insights into decision making mechanisms in general. From an engineering viewpoint, we propose that the model could be applied to a wider range of decision making practices. PMID:22300450

  6. Hybrid Molecular and Spin-Semiconductor Based Research

    DTIC Science & Technology

    2005-02-02

    13. ABSTRACT (Maximum 200 words) This project has three thrusts. Thrust I is entitled “Integrated Bacteriorhodopsin -Based Photodetectors...studied Thrust I: Integrated Bacteriorhodopsin -Based Photodetectors The objective of this thrust was to enable a new class of optoelectronic devices by...nature of Bacteriorhodopsin (bR) have been utilized to construct novel molecular sensors, modulators, or imaging devices. The light induced photovoltage

  7. 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.

  8. 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.

  9. NEW MOLECULAR MEDICINE-BASED SCAR MANAGEMENT STRATEGIES

    PubMed Central

    Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G

    2014-01-01

    Keloids and hypertrophic scars are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research has contributed to unravel new bench-to-bedside scar therapies, and to dissect the complex signaling pathways involved. Peptides such as transforming growth factor beta (TGF-β) superfamily, with SMADs, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-β4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scars. The aim of this review is to describe the basic complexity of these new molecular scar management strategies, and point out new fibrosis research lines. PMID:24438742

  10. [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.

  11. A molecular shift register based on electron transfer

    NASA Technical Reports Server (NTRS)

    Hopfield, J. J.; Onuchic, Josenelson; Beratan, David N.

    1988-01-01

    An electronic shift-register memory at the molecular level is described. The memory elements are based on a chain of electron-transfer molecules and the information is shifted by photoinduced electron-transfer reactions. This device integrates designed electronic molecules onto a very large scale integrated (silicon microelectronic) substrate, providing an example of a 'molecular electronic device' that could actually be made. The design requirements for such a device and possible synthetic strategies are discussed. Devices along these lines should have lower energy usage and enhanced storage density.

  12. 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.

  13. A molecular shift register based on electron transfer

    NASA Technical Reports Server (NTRS)

    Hopfield, J. J.; Onuchic, Josenelson; Beratan, David N.

    1988-01-01

    An electronic shift-register memory at the molecular level is described. The memory elements are based on a chain of electron-transfer molecules and the information is shifted by photoinduced electron-transfer reactions. This device integrates designed electronic molecules onto a very large scale integrated (silicon microelectronic) substrate, providing an example of a 'molecular electronic device' that could actually be made. The design requirements for such a device and possible synthetic strategies are discussed. Devices along these lines should have lower energy usage and enhanced storage density.

  14. 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.

  15. Optically induced transport through semiconductor-based molecular electronics

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    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.

  16. 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.

  17. Nanocoax-based molecular imprint polymer for electrochemical biosensor

    NASA Astrophysics Data System (ADS)

    Rizal, Binod; Archibald, Michelle; Simko, Laura; Connolly, Timothy; Shepard, Stephen; Burns, Michael; Chiles, Thomas; Naughton, Michael

    2013-03-01

    We have used molecular imprint polymerization (MIP) on planar, nanopillar, and nanocoax structures to fabricate label-free, all-electronic electrochemical biosensors with high selectivity and sensitivity. MIP-based films of ~ 7 nm thickness are formed on gold-coated surfaces by electropolymerization of a solution containing phenol and a target protein (streptavidin, at 100 μg/ml, or 1 nanomole concentration) and subsequent removal of exposed target protein, leaving behind its molecular imprint. With its molecular memory, MIP subsequently specifically recognizes and binds target protein with attomolar sensitivity, detected via differential pulse voltammetry. We will discuss and compare the results of MIP for different proteins on planar, nanopillar, and nanocoax structures, along with their respective ultimate sensitivities. Supported by the NIH grants NCI CA137681 and NIAID AI100216.

  18. Molecular-genetic imaging based on reporter gene expression.

    PubMed

    Kang, Joo Hyun; Chung, June-Key

    2008-06-01

    Molecular imaging includes proteomic, metabolic, cellular biologic process, and genetic imaging. In a narrow sense, molecular imaging means genetic imaging and can be called molecular-genetic imaging. Imaging reporter genes play a leading role in molecular-genetic imaging. There are 3 major methods of molecular-genetic imaging, based on optical, MRI, and nuclear medicine modalities. For each of these modalities, various reporter genes and probes have been developed, and these have resulted in successful transitions from bench to bedside applications. Each of these imaging modalities has its unique advantages and disadvantages. Fluorescent and bioluminescent optical imaging modalities are simple, less expensive, more convenient, and more user friendly than other imaging modalities. Another advantage, especially of bioluminescence imaging, is its ability to detect low levels of gene expression. MRI has the advantage of high spatial resolution, whereas nuclear medicine methods are highly sensitive and allow data from small-animal imaging studies to be translated to clinical practice. Moreover, multimodality imaging reporter genes will allow us to choose the imaging technologies that are most appropriate for the biologic problem at hand and facilitate the clinical application of reporter gene technologies. Reporter genes can be used to visualize the levels of expression of particular exogenous and endogenous genes and several intracellular biologic phenomena, including specific signal transduction pathways, nuclear receptor activities, and protein-protein interactions. This technique provides a straightforward means of monitoring tumor mass and can visualize the in vivo distributions of target cells, such as immune cells and stem cells. Molecular imaging has gradually evolved into an important tool for drug discovery and development, and transgenic mice with an imaging reporter gene can be useful during drug and stem cell therapy development. Moreover, instrumentation

  19. Molecular biomimetics: GEPI-based biological routes to technology.

    PubMed

    Tamerler, Candan; Khatayevich, Dmitriy; Gungormus, Mustafa; Kacar, Turgay; Oren, E Emre; Hnilova, Marketa; Sarikaya, Mehmet

    2010-01-01

    In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage display methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and biological materials. Here, we

  20. 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.

  1. Molecular crowding-based imprinted monolithic column for capillary electrochromatography.

    PubMed

    Zong, Hai-Yan; Liu, Xiao; Liu, Zhao-Sheng; Huang, Yan-Ping

    2015-03-01

    Molecular crowding is a new approach to stabilizing binding sites and improving molecular recognition. In this work, the concept was applied to the preparation of imprinted monolithic columns for CEC. The imprinted monolithic column was synthesized using a mixture of d-zopiclone (d-ZOP)(template), methacrylic acid, ethylene glycol dimethacrylate, and poly(methyl methacrylate) (PMMA) (molecular crowding agent). The resulting PMMA-based imprinted capillary was able to separate ZOP enantiomers in CEC mode. The resolution of enantiomer separation achieved on the d-ZOP-imprinted monolithic column was up to 2.09. Some polymerization factors, such as template-monomer molar ratio, functional monomer-cross-linker molar ratio and the composition of the porogen, on the imprinting effect of resulting molecularly imprinted polymer (MIP) monolithic column were systematically investigated. Chromatographic parameters, including pH values, the content of acetonitrile and the salt concentration on chiral separation were also studied. The results indicated the addition of PMMA resulted in MIPs with superior retention properties and excellent selectivity for d-ZOP, as compared to the MIPs prepared without addition of the crowding-inducing agent. The results revealed that molecular crowding is an effective method for the preparation of a highly efficient MIP stationary phase for chiral separation in CEC.

  2. [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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

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

    DOE PAGES

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; ...

    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

  9. 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.

  10. Standardised PCR-based molecular epidemiology of tuberculosis.

    PubMed

    Allix-Béguec, C; Supply, P; Wanlin, M; Bifani, P; Fauville-Dufaux, M

    2008-05-01

    A population-based molecular epidemiology investigation has been undertaken to evaluate tuberculosis transmission and control in the Brussels-Capital Region (Belgium). All tuberculosis cases reported from January 2003 to December 2004 were investigated. In total, 536 Mycobacterium tuberculosis isolates (89% of culture-positive samples) were genotyped by the newly standardised 24 loci-based mycobacterial interspersed repetitive unit-variable number tandem-repeat typing, spoligotyping and IS6110 fingerprinting. Of all the patients, 30% were grouped based on strain clusters, suggesting a transmission index of 20%. An unsuspected outbreak entailing > or = 23 patients was evidenced by molecular typing analysis and confirmed by contact tracing. Foreign-born status accounted for 79% of the studied patients, including 37.9% illegal immigrants and asylum seekers. Among foreign-born patients, asylum seekers and illegal immigrants were significantly less abundant in strain clusters than settled residents. Tuberculosis in the Brussels-Capital Region is a bi-faceted problem, comprising both persisting recent transmission and "imported diseases". Molecular epidemiology based on real-time genotyping techniques has proven invaluable in better understanding tuberculosis transmission. However, it will most efficiently contribute to tuberculosis control when implemented in an integrated public health system.

  11. Molecular Dynamics Simulations of Perylenediimide DNA Base Surrogates.

    PubMed

    Markegard, Cade B; Mazaheripour, Amir; Jocson, Jonah-Micah; Burke, Anthony M; Dickson, Mary N; Gorodetsky, Alon A; Nguyen, Hung D

    2015-09-03

    Perylene-3,4,9,10-tetracarboxylic diimides (PTCDIs) are a well-known class of organic materials. Recently, these molecules have been incorporated within DNA as base surrogates, finding ready applications as probes of DNA structure and function. However, the assembly dynamics and kinetics of PTCDI DNA base surrogates have received little attention to date. Herein, we employ constant temperature molecular dynamics simulations to gain an improved understanding of the assembly of PTCDI dimers and trimers. We also use replica-exchange molecular dynamics simulations to elucidate the energetic landscape dictating the formation of stacked PTCDI structures. Our studies provide insight into the equilibrium configurations of multimeric PTCDIs and hold implications for the construction of DNA-inspired systems from perylene-derived organic semiconductor building blocks.

  12. A molecular-based magnet test for malaria.

    PubMed

    Nalbandian, R M; Sammons, D W; Manley, M; Xie, L; Sterling, C R; Egen, N B; Gingras, B A

    1995-01-01

    The molecular-based magnet test for malaria is shown to be more sensitive than the thin blood film test. The globally used thin blood film test is less sensitive because it uses preparation steps that result in the reduction of the absolute number of diagnostically pertinent erythrocytes. Several reports of diagnostic error with the thin film test and the thick film test have appeared in the literature. In marked contrast to the commonly accepted tests, the magnet test concurrently partitions and concentrates the infected erythrocytes present in the initial sample. The magnetic test permits a brief and sensitive microscopic-based enumeration of the malaria-infected erythrocytes in the enriched sample. Diagnostically pertinent hemozoin is simply identified through two of its specific molecular properties: paramagnetism and birefringence. The former property mediates the capture and enrichment of malaria-infected erythrocytes within the magnetic flux and the latter property manifests the characteristic birefringence demonstrated by polarized light.

  13. 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

  14. 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.

  15. Envisioning the molecular choreography of DNA base excision repair.

    PubMed

    Parikh, S S; Mol, C D; Hosfield, D J; Tainer, J A

    1999-02-01

    Recent breakthroughs integrate individual DNA repair enzyme structures, biochemistry and biology to outline the structural cell biology of the DNA base excision repair pathways that are essential to genome integrity. Thus, we are starting to envision how the actions, movements, steps, partners and timing of DNA repair enzymes, which together define their molecular choreography, are elegantly controlled by both the nature of the DNA damage and the structural chemistry of the participating enzymes and the DNA double helix.

  16. Del Xq23 in a mosaic Turner female: molecular and cytogenetic studies.

    PubMed

    Mesa-Cornejo, V M; García-Cruz, D; Monroy-Jaramillo, N; Vásquez, A I; Dávalos, N O; Galaviz, C; Kofman, S

    2001-01-01

    We report a Turner patient aged 22 years with a 45,X/46,X,del(X)(q23) karyotype. Late replication studies showed preferential inactivation of the deleted X chromosome; FISH studies with a probe for total human telomeres showed hybridisation signal in the telomeres on both the normal and the deleted X chromosomes. Microsatellite analysis in the proposita and her family permitted us to conclude to the maternal origin of the deleted X chromosome, and to detect using the marker DXS1106 (Xq22) a probable meiotic recombination event above the breakage point suggesting that the deletion occurred underneath this point. The mild Turner stigmata may be explained by the 45,X cell line, and the gonadal dysgenesis probably by a partial deletion of the gonadal dysgenesis region Xq13-q23 (excluding Xq22).

  17. 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

  18. 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.

  19. A Molecular Selection Index Method Based on Eigenanalysis

    PubMed Central

    Cerón-Rojas, J. Jesús; Castillo-González, Fernando; Sahagún-Castellanos, Jaime; Santacruz-Varela, Amalio; Benítez-Riquelme, Ignacio; Crossa, José

    2008-01-01

    The traditional molecular selection index (MSI) employed in marker-assisted selection maximizes the selection response by combining information on molecular markers linked to quantitative trait loci (QTL) and phenotypic values of the traits of the individuals of interest. This study proposes an MSI based on an eigenanalysis method (molecular eigen selection index method, MESIM), where the first eigenvector is used as a selection index criterion, and its elements determine the proportion of the trait's contribution to the selection index. This article develops the theoretical framework of MESIM. Simulation results show that the genotypic means and the expected selection response from MESIM for each trait are equal to or greater than those from the traditional MSI. When several traits are simultaneously selected, MESIM performs well for traits with relatively low heritability. The main advantages of MESIM over the traditional molecular selection index are that its statistical sampling properties are known and that it does not require economic weights and thus can be used in practical applications when all or some of the traits need to be improved simultaneously. PMID:18716338

  20. Molecular switching behavior in isosteric DNA base pairs.

    PubMed

    Jissy, A K; Konar, Sukanya; Datta, Ayan

    2013-04-15

    The structures and proton-coupled behavior of adenine-thymine (A-T) and a modified base pair containing a thymine isostere, adenine-difluorotoluene (A-F), are studied in different solvents by dispersion-corrected density functional theory. The stability of the canonical Watson-Crick base pair and the mismatched pair in various solvents with low and high dielectric constants is analyzed. It is demonstrated that A-F base pairing is favored in solvents with low dielectric constant. The stabilization and conformational changes induced by protonation are also analyzed for the natural as well as the mismatched base pair. DNA sequences capable of changing their sequence conformation on protonation are used in the construction of pH-based molecular switches. An acidic medium has a profound influence in stabilizing the isostere base pair. Such a large gain in stability on protonation leads to an interesting pH-controlled molecular switch, which can be incorporated in a natural DNA tract.

  1. 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.

  2. 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

  3. Genetic analysis and molecular characterization of Chinese sesame (Sesamum indicum L.) cultivars using insertion-deletion (InDel) and simple sequence repeat (SSR) markers.

    PubMed

    Wu, Kun; Yang, Minmin; Liu, Hongyan; Tao, Ye; Mei, Ju; Zhao, Yingzhong

    2014-03-19

    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. 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. 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, reflecting the effect of genetic

  4. 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.

  5. 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.

  6. Programmable molecular recognition based on the geometry of DNA nanostructures

    NASA Astrophysics Data System (ADS)

    Woo, Sungwook; Rothemund, Paul W. K.

    2011-08-01

    From ligand-receptor binding to DNA hybridization, molecular recognition plays a central role in biology. Over the past several decades, chemists have successfully reproduced the exquisite specificity of biomolecular interactions. However, engineering multiple specific interactions in synthetic systems remains difficult. DNA retains its position as the best medium with which to create orthogonal, isoenergetic interactions, based on the complementarity of Watson-Crick binding. Here we show that DNA can be used to create diverse bonds using an entirely different principle: the geometric arrangement of blunt-end stacking interactions. We show that both binary codes and shape complementarity can serve as a basis for such stacking bonds, and explore their specificity, thermodynamics and binding rules. Orthogonal stacking bonds were used to connect five distinct DNA origami. This work, which demonstrates how a single attractive interaction can be developed to create diverse bonds, may guide strategies for molecular recognition in systems beyond DNA nanostructures.

  7. Molecular-based choice of cancer therapy: realities and expectations.

    PubMed

    Imyanitov, Evgeny N; Moiseyenko, Vladimir M

    2007-04-01

    Current choice of cancer therapy is usually empirical and relies mainly on the statistical prediction of the treatment success. Molecular research provides some opportunities to personalize antitumor treatment. For example, life-threatening toxic reactions can be avoided by the identification of subjects, who carry susceptible genotypes of drug-metabolizing genes (e.g. TPMT, UGT1A1, MTHFR, DPYD). Tumor sensitivity can be predicted by molecular portraying of targets and other molecules associated with drug response. Tailoring of antiestrogen and trastuzumab therapy based on hormone and HER2 receptor status has already become a classical example of customized medicine. Other predictive markers have been identified both for cytotoxic and for targeted therapies, and include, for example, expression of TS, TP, DPD, OPRT, ERCC1, MGMT, TOP2A, class III beta-tubulin molecules as well as genomic alterations of EGFR, KIT, ABL oncogenes.

  8. Competency-Based Education for the Molecular Genetic Pathology Fellow

    PubMed Central

    Talbert, Michael L.; Dunn, S. Terence; Hunt, Jennifer; Hillyard, David R.; Mirza, Imran; Nowak, Jan A.; Van Deerlin, Vivianna; Vnencak-Jones, Cindy L.

    2009-01-01

    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. PMID:19797613

  9. Affinity sensor based on immobilized molecular imprinted synthetic recognition elements.

    PubMed

    Lenain, Pieterjan; De Saeger, Sarah; Mattiasson, Bo; Hedström, Martin

    2015-07-15

    An affinity sensor based on capacitive transduction was developed to detect a model compound, metergoline, in a continuous flow system. This system simulates the monitoring of low-molecular weight organic compounds in natural flowing waters, i.e. rivers and streams. During operation in such scenarios, control of the experimental parameters is not possible, which poses a true analytical challenge. A two-step approach was used to produce a sensor for metergoline. Submicron spherical molecularly imprinted polymers, used as recognition elements, were obtained through emulsion polymerization and subsequently coupled to the sensor surface by electropolymerization. This way, a robust and reusable sensor was obtained that regenerated spontaneously under the natural conditions in a river. Small organic compounds could be analyzed in water without manipulating the binding or regeneration conditions, thereby offering a viable tool for on-site application.

  10. 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

  11. 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

  12. Clinical and molecular cytogenetic studies in ten patients with hematological malignancies characterized by t(20;21)(q11;q11) resulted from del(20q).

    PubMed

    Wu, Chunxiao; Zhang, Jun; Bai, Shuxiao; Yao, Jianxin; Qiu, Huiying; Xue, Yongquan; Chen, Suning; Wu, Yafang; Shen, Juan; Pan, Jinlan

    2016-10-01

    This study reports 10 patients with hematological malignances with t(20;21)(q11;q11) resulting from del(20q) (for example, der(20)del(20)(q11q13)t(20;21)(q11;q11) and der(21)t(20;21)(q11;q11)) and described their clinical features and the possible prognostic significance of this abnormality. The t(20;21)(q11;q11) was a rare but recurrent abnormality secondary to del(20q) besides i(20q-). The frequency of der(20)del(20)(q11q13)t(20;21)(q11;q11) among our patients with del(20q) was 2.4%. It was considered that the 20q deletion preceded translocation with chromosome 21. This abnormality is often cryptic, occurs predominantly in older men and is observed most often in myelodysplastic syndromes. Patients with this abnormality have an unfavorable prognosis, similar to patients with i(20q-). The molecular consequences of der(20)del(20)(q11q13)t(20;21)(q11;q11) may be different from patients with i(20q-). To the best of our knowledge this is the largest dataset published to date.

  13. 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.

  14. Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

    PubMed

    Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

    2016-04-01

    With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

  15. Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials

    PubMed Central

    Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

    2016-01-01

    With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients’ tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. PMID:26598514

  16. Polarizable Atomic Multipole-based Molecular Mechanics for Organic Molecules

    PubMed Central

    Ren, Pengyu; Wu, Chuanjie; Ponder, Jay W.

    2011-01-01

    An empirical potential based on permanent atomic multipoles and atomic induced dipoles is reported for alkanes, alcohols, amines, sulfides, aldehydes, carboxylic acids, amides, aromatics and other small organic molecules. Permanent atomic multipole moments through quadrupole moments have been derived from gas phase ab initio molecular orbital calculations. The van der Waals parameters are obtained by fitting to gas phase homodimer QM energies and structures, as well as experimental densities and heats of vaporization of neat liquids. As a validation, the hydrogen bonding energies and structures of gas phase heterodimers with water are evaluated using the resulting potential. For 32 homo- and heterodimers, the association energy agrees with ab initio results to within 0.4 kcal/mol. The RMS deviation of hydrogen bond distance from QM optimized geometry is less than 0.06 Å. In addition, liquid self-diffusion and static dielectric constants computed from molecular dynamics simulation are consistent with experimental values. The force field is also used to compute the solvation free energy of 27 compounds not included in the parameterization process, with a RMS error of 0.69 kcal/mol. The results obtained in this study suggest the AMOEBA force field performs well across different environments and phases. The key algorithms involved in the electrostatic model and a protocol for developing parameters are detailed to facilitate extension to additional molecular systems. PMID:22022236

  17. Molecular Bases Underlying the Hepatoprotective Effects of Coffee

    PubMed Central

    Salomone, Federico; Galvano, Fabio; Li Volti, Giovanni

    2017-01-01

    Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation. PMID:28124992

  18. Molecular Bases Underlying the Hepatoprotective Effects of Coffee.

    PubMed

    Salomone, Federico; Galvano, Fabio; Li Volti, Giovanni

    2017-01-23

    Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.

  19. Diamondoid-based molecular junctions: a computational study

    NASA Astrophysics Data System (ADS)

    Adhikari, Bibek; Sivaraman, Ganesh; Fyta, Maria

    2016-12-01

    In this work, we deal with the computational investigation of diamondoid-based molecular conductance junctions and their electronic transport properties. A small diamondoid is placed between the two gold electrodes of the nanogap and is covalently bonded to the gold electrodes through two different molecules, a thiol group and a N-heterocyclic carbene molecule. We have shown that the thiol linker is more efficient as it introduces additional electron paths for transport at lower energies. The influence of doping the diamondoid on the properties of the molecular junctions has been investigated. We find that using a nitrogen atom to dope the diamondoids leads to a considerable increase of the zero bias conductance. For the N-doped system we show an asymmetric feature of the I-V curve of the junctions resulting in rectification within a very small range of bias voltages. The rectifying nature is the result of the characteristic shift in the bias-dependent highest occupied molecular orbital state. In all cases, the efficiency of the device is manifested and is discussed in view of novel nanotechnological applications.

  20. Polarizable Atomic Multipole-based Molecular Mechanics for Organic Molecules.

    PubMed

    Ren, Pengyu; Wu, Chuanjie; Ponder, Jay W

    2011-10-11

    An empirical potential based on permanent atomic multipoles and atomic induced dipoles is reported for alkanes, alcohols, amines, sulfides, aldehydes, carboxylic acids, amides, aromatics and other small organic molecules. Permanent atomic multipole moments through quadrupole moments have been derived from gas phase ab initio molecular orbital calculations. The van der Waals parameters are obtained by fitting to gas phase homodimer QM energies and structures, as well as experimental densities and heats of vaporization of neat liquids. As a validation, the hydrogen bonding energies and structures of gas phase heterodimers with water are evaluated using the resulting potential. For 32 homo- and heterodimers, the association energy agrees with ab initio results to within 0.4 kcal/mol. The RMS deviation of hydrogen bond distance from QM optimized geometry is less than 0.06 Å. In addition, liquid self-diffusion and static dielectric constants computed from molecular dynamics simulation are consistent with experimental values. The force field is also used to compute the solvation free energy of 27 compounds not included in the parameterization process, with a RMS error of 0.69 kcal/mol. The results obtained in this study suggest the AMOEBA force field performs well across different environments and phases. The key algorithms involved in the electrostatic model and a protocol for developing parameters are detailed to facilitate extension to additional molecular systems.

  1. Structure-based molecular modeling approaches to GPCR oligomerization.

    PubMed

    Kaczor, Agnieszka A; Selent, Jana; Poso, Antti

    2013-01-01

    Classical structure-based drug design techniques using G-protein-coupled receptors (GPCRs) as targets focus nearly exclusively on binding at the orthosteric site of a single receptor. Dimerization and oligomerization of GPCRs, proposed almost 30 years ago, have, however, crucial relevance for drug design. Targeting these complexes selectively or designing small molecules that affect receptor-receptor interactions might provide new opportunities for novel drug discovery. In order to study the mechanisms and dynamics that rule GPCRs oligomerization, it is essential to understand the dynamic process of receptor-receptor association and to identify regions that are suitable for selective drug binding, which may be determined with experimental methods such as Förster resonance energy transfer (FRET) or Bioluminescence resonance energy transfer (BRET) and computational sequence- and structure-based approaches. The aim of this chapter is to provide a comprehensive description of the structure-based molecular modeling methods for studying GPCR dimerization, that is, protein-protein docking, molecular dynamics, normal mode analysis, and electrostatics studies.

  2. Molecular imprinting sensor based on quantum weak measurement.

    PubMed

    Li, Dongmei; He, Qinghua; He, Yonghong; Xin, Meiguo; Zhang, Yilong; Shen, Zhiyuan

    2017-03-10

    A new type of sensing protocol, based on a high precision metrology of quantum weak measurement, was first proposed for molecularly imprinted polymers (MIP) sensor. The feasibility, sensitivity and selectivity of weak measurement based MIP (WMMIP) sensor were experimentally demonstrated with bovine serum albumin (BSA). Weak measurement system exhibits high sensitivity to the optical phase shift corresponding to the refractive index change, which is induced by the specific capture of target protein molecules with its recognition sites. The recognition process can be finally characterized by the central wavelength shift of output spectra through weak value amplification. In our experiment, we prepared BSA@MIP with modified reversed-phase microemulsion method, and coated it on the internal surface of measuring channels assembled into the Mach-Zehnder (MZ) interferometer based optical weak measurement system. The design of this home-built optical system makes it possible to detect analyte in real time. The dynamic process of the specific adsorption and concentration response to BSA from 5×10(-4) to 5×10(-1)μg/L was achieved with a limit of detection (LOD) of 8.01×10(-12)g/L. This WMMIP shows superiority in accuracy, fast response and low cost. Furthermore, real-time monitoring system can creatively promote the performance of MIP in molecular analysis.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  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. Mesoporous Silica Molecular Sieve based Nanocarriers: Transpiring Drug Dissolution Research.

    PubMed

    Pattnaik, Satyanarayan; Pathak, Kamla

    2017-01-01

    Improvement of oral bioavailability through enhancement of dissolution for poorly soluble drugs has been a very promising approach. Recently, mesoporous silica based molecular sieves have demonstrated excellent properties to enhance the dissolution velocity of poorly water-soluble drugs. Current research in this area is focused on investigating the factors influencing the drug release from these carriers, the kinetics of drug release and manufacturing approaches to scale-up production for commercial manufacture. This comprehensive review provides an overview of different methods adopted for synthesis of mesoporous materials, influence of processing factors on properties of these materials and drug loading methods. The drug release kinetics from mesoporous silica systems, the manufacturability and stability of these formulations are reviewed. Finally, the safety and biocompatibility issues related to these silica based materials are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

    PubMed

    Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

    2016-02-01

    Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

  11. A molecularly based theory for electron transfer reorganization energy.

    PubMed

    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.

  12. 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

  13. Xerogel-based molecularly imprinted polymers for explosives detection

    NASA Astrophysics Data System (ADS)

    Holthoff, Ellen L.; Stratis-Cullum, Dimitra N.; Hankus, Mikella E.

    2010-04-01

    Molecularly imprinted polymers (MIPs) can be utilized as artificial recognition elements for target chemical analytes of interest. Molecular imprinting involves arranging polymerizable functional monomers around a template followed by polymerization and template removal. The selectivity for the target analyte is based on the spatial orientation of the binding site and covalent or noncovalent interactions between the functional monomer and the analyte. The polymer materials of particular interest are sol-gel-derived xerogels. To allow for increased target recognition, the xerogel has specific functional groups, which allow for polymer interactions with the template molecule (and target analyte). In a sensor format, the recognition event is monitored with some form of transduction. MIP technology is still in its infancy and limitations such as non-specific binding may be overcome utilizing surface enhanced Raman scattering (SERS) as an integrated transduction method for enhanced sensor performance. The objective of the present work is to create a sensitive and selective MIP-SERS sensing platform for 2,4,6-trinitrotoluene (TNT).

  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. Advanced synchrotron-based and globar-sourced molecular (micro) spectroscopy contributions to advances in food and feed research on molecular structure, mycotoxin determination, and molecular nutrition.

    PubMed

    Shi, Haitao; Yu, Peiqiang

    2017-04-17

    Mycotoxin contamination has been a worldwide problem for food and feeds production for a long time. There is an obviously increased focus of the food and feed industry toward the reduction of mycotoxin concentration in both the raw materials and finished products. Therefore, both effective qualitative and quantitative techniques for the determination of mycotoxins are required to minimize their harmful effects. Conventional wet chemical methods usually are time-consuming, expensive, and rely on complex extraction and cleanup pretreatments. Synchrotron-based and globar-based molecular spectroscopy have shown great potential to be developed as rapid and nondestructive tools for the determination of molecular structure, molecular nutrition and mycotoxins in feed and food. This article reviews the common types of mycotoxins in feed and food, their toxicity, as well as the conventional detection methods. The principle of advanced molecular spectroscopy techniques and their application prospects for mycotoxin detection are discussed. Recent progress in food and feed research with molecular spectroscopy techniques is highlighted. This review provides a potential and insight into how to determine the structure and mycotoxins of feed and food on a molecular basis with advanced Synchrotron-based and globar-based molecular (micro) spectroscopy.

  16. 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.

  17. [Targeted molecular therapy based on advanced cancer stem cell model].

    PubMed

    Hirao, Atsushi

    2015-08-01

    Improvement of cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TICs). Although it was hypothesized that tumors are organized as hierarchies of tumor cells that are sustained by rare TICs, like normal tissue stem cells, there are several controversies towards such cancer stem cell model, e.g. reversible change of stem cell like population based on epigenetic changes, clonal genetic evolution and problems in xenotransplantation system. Despite complexity in cancer stem cell models, studies in cancer stem cell field have revealed that there are close relationship between cancer malignancy and stem cell properties, called "stemness". Understanding molecular mechanisms for controlling stemness would contribute to establishment of novel diagnostics or therapeutics for cancer.

  18. 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

  19. 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.

  20. Communication: Quantum Zeno-based control mechanism for molecular fragmentation

    NASA Astrophysics Data System (ADS)

    Sanz-Sanz, C.; Sanz, A. S.; González-Lezana, T.; Roncero, O.; Miret-Artés, S.

    2012-03-01

    A quantum control mechanism is proposed for molecular fragmentation processes within a scenario grounded on the quantum Zeno effect. In particular, we focus on the van der Waals Ne-Br2 complex, which displays two competing dissociation channels via vibrational and electronic predissociation. Accordingly, realistic three-dimensional wave packet simulations are carried out by using ab initio interaction potentials recently obtained to reproduce available experimental data. Two numerical models to simulate the repeated measurements are reported and analyzed. It is found that the otherwise fast vibrational predissociation is slowed down in favor of the slow electronic (double fragmentation) predissociation, which is enhanced by several orders of magnitude. Based on these theoretical predictions, some hints to experimentalists to confirm their validity are also proposed.

  1. Hydrophobic composition based on mixed-molecular weight polyethylene

    NASA Astrophysics Data System (ADS)

    Gorlenko, Nikolay; Debelova, Natalya; Sarkisov, Yuriy; Volokitin, Gennadiy; Zavyalova, Elena; Lapova, Tatyana

    2016-01-01

    The paper presents investigations of compositions based on low and high molecular weight polyethylene so as to synthesize a hydrophobic composition for moisture protection of timber. X-ray phase analysis and measurements of the tear-off force of hydrophobic coating needed to apply to the timber surface and the limiting wetting angle are carried out to detect the hydrophobic, adhesive, electrophysical, and physicochemical properties of compositions. Kinetic dependencies are given for moisture absorption of timber specimens. It is shown that the preliminary formation of the texture by the surface patterning or its treatment with low-temperature plasma with the following protective coating results in the improvement of hydrophobic properties of the suggested compositions. These compositions can be used in the capacity of water repellents to protect building materials from moisture including restoration works.

  2. 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

  3. Molecular pincers – new antibody-based homogenous protein sensors

    PubMed Central

    Heyduk, Ewa; Dummit, Benjamin; Chang, Yie-Hwa; Heyduk, Tomasz

    2008-01-01

    We describe here a new homogenous antibody-based protein sensor design (molecular pincers) that allows rapid and sensitive detection of a specific protein in solution. In the presence of the target protein these sensors produce fluorescence signal derived from target-dependent annealing of short complementary fluorochrome-labeled oligonucleotides attached to a pair of target-specific antibodies via nanometer-scale flexible linkers. The sensors allow near-instantaneous detection of the target with sensitivity and specificity approaching ELISA but requiring no sample manipulation other then the addition of the sample to the sensor mix. We used cardiac troponin I and C-reactive protein as the targets to validate these desirable properties of the sensors. Due to the availability of antibodies to thousands of interesting targets and the straightforward design blueprint of the sensors we expect their wide-ranging applications in research and medical diagnosis, especially when simplicity, high throughput, and short detection time are essential. PMID:18491925

  4. Current Progress of Aptamer-Based Molecular Imaging

    PubMed Central

    Wang, Andrew Z.; Farokhzad, Omid C.

    2014-01-01

    Aptamers, single-stranded oligonucleotides, are an important class of molecular targeting ligand. Since their discovery, aptamers have been rapidly translated into clinical practice. They have been approved as therapeutics and molecular diagnostics. Aptamers also possess several properties that make them uniquely suited to molecular imaging. This review aims to provide an overview of aptamers’ advantages as targeting ligands and their application in molecular imaging. PMID:24525205

  5. 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.

  6. Development of EST-based SNP and InDel markers and their utilization in tetraploid cotton genetic mapping

    USDA-ARS?s Scientific Manuscript database

    Expressed sequence tags (ESTs) were analyzed in silico in order to identify single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (InDels) in cotton. A total of 1349 EST-based SNP and InDel markers were developed by comparing ESTs between Gossypium hirsutum and G. barbadense, m...

  7. 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.

  8. 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

    2014-05-06

    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.

  9. 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.

  10. A tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation

    NASA Astrophysics Data System (ADS)

    Caracelli, Ignez; Vega-Teijido, Mauricio; Zukerman-Schpector, Julio; Cezari, Maria H. S.; Lopes, José G. S.; Juliano, Luiz; Santos, Paulo S.; Comasseto, João V.; Cunha, Rodrigo L. O. R.; Tiekink, Edward R. T.

    2012-04-01

    The crystallographically determined structure of biologically active 4,4-dichloro-1,3-diphenyl-4-telluraoct-2-en-1-one, 3, shows the coordination geometry for Te to be distorted ψ-pentagonal bipyramidal based on a C2OCl3(lone pair) donor set. Notable is the presence of an intramolecular axial Te⋯O(carbonyl) interaction, a design element included to reduce hydrolysis. Raman and molecular modelling studies indicate the persistence of the Te⋯O(carbonyl) interaction in the solution (CHCl3) and gas-phases, respectively. Docking studies of 3' (i.e. original 3 less one chloride) with Cathepsin B reveals a change in the configuration about the vinyl Cdbnd C bond, i.e. to E from Z (crystal structure). This isomerism allows the optimisation of interactions in the complex which features a covalent Tesbnd SGCys29 bond. Crucially, the E configuration observed for 3' allows for the formation of a hypervalent Te⋯O interaction as well as an O⋯Hsbnd O hydrogen bond with the Gly27 and Glu122 residues, respectively. Additional stabilisation is afforded by a combination of interactions spanning the S1, S2, S1' and S2' sub-sites of Cathepsin B. The greater experimental inhibitory activity of 3 compared with analogues is rationalised by the additional interactions formed between 3' and the His110 and His111 residues in the occluding loop, which serve to hinder the entrance to the active site.

  11. 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.

  12. Molecular based equation of state for shocked liquid nitromethane.

    PubMed

    Desbiens, Nicolas; Bourasseau, Emeric; Maillet, Jean-Bernard; Soulard, Laurent

    2009-07-30

    An approach is proposed to obtain the equation of state of unreactive shocked liquid nitromethane. Unlike previous major works, this equation of state is not based on extended integration schemes [P.C. Lysne, D.R. Hardesty, Fundamental equation of state of liquid nitromethane to 100 kbar, J. Chem. Phys. 59 (1973) 6512]. It does not follow the way proposed by Winey et al. [J.M. Winey, G.E. Duvall, M.D. Knudson, Y.M. Gupta, Equation of state and temperature measurements for shocked nitromethane, J. Chem. Phys. 113 (2000) 7492] where the specific heat C(v), the isothermal bulk modulus B(T) and the coefficient of thermal pressure (deltaP/deltaT)(v) are modeled as functions of temperature and volume using experimental data. In this work, we compute the complete equation of state by microscopic calculations. Indeed, by means of Monte Carlo molecular simulations, we have proposed a new force field for nitromethane that lead to a good description of shock properties [N. Desbiens, E. Bourasseau, J.-B. Maillet, Potential optimization for the calculation of shocked liquid nitromethane properties, Mol. Sim. 33 (2007) 1061; A. Hervouët, N. Desbiens, E. Bourasseau, J.-B. Maillet, Microscopic approaches to liquid nitromethane detonation properties, J. Phys. Chem. B 112 (2008) 5070]. Particularly, it has been shown that shock temperatures and second shock temperatures are accurately reproduced which is significative of the quality of the potential. Here, thermodynamic derivative properties are computed: specific heats, Grüneisen parameter, sound velocity among others, along the Hugoniot curve. This work constitutes to our knowledge the first determination of the equation of state of an unreactive shocked explosive by molecular simulations.

  13. Molecular imaging based on metabolic glycoengineering and bioorthogonal click chemistry.

    PubMed

    Yoon, Hong Yeol; Koo, Heebeom; Kim, Kwangmeyung; Kwon, Ick Chan

    2017-07-01

    Metabolic glycoengineering is a powerful technique that can introduce various chemical groups to cellular glycan by treatment of unnatural monosaccharide. Particularly, this technique has enabled many challenging trials for molecular imaging in combination with click chemistry, which provides fast and specific chemical conjugation reaction of imaging probes to metabolically-modified live cells. This review introduces recent progress in molecular imaging based on the combination of these two cutting-edge techniques. First, these techniques showed promising results in specific tumor cell imaging for cancer diagnosis and therapy. The related researches showed the surface of tumor cells could be labeled with bioorthogonal chemical groups by metabolic glycoengineering, which can be further conjugated with fluorescence dyes or nanoparticles with imaging probes by click chemistry, in vitro and in vivo. This method can be applied to heterogeneous tumor cells regardless of genetic properties of different tumor cells. Furthermore, the amount of targeting moieties on tumor cells can be freely controlled externally by treatment of unnatural monosaccharide. Second, this sequential use of metabolic glycoengineering and click chemistry is also useful in cell tracking to monitor the localization of the inoculated therapeutic cells including chondrocytes and stem cells. This therapeutic cell-labeling technique provided excellent viability of chondrocytes and stem cells during the whole process in vitro and in vivo. It can provide long-term and safe therapeutic cell imaging compared to traditional methods. These overall studies demonstrate the great potential of metabolic glycoengineering and click chemistry in live cell imaging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique

    PubMed Central

    Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

    2017-01-01

    In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed. PMID:28445393

  15. Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique.

    PubMed

    Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

    2017-04-26

    In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed.

  16. Pathological Bases for a Robust Application of Cancer Molecular Classification

    PubMed Central

    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

  17. Magnetic and electronic properties of porphyrin-based molecular nanowires

    NASA Astrophysics Data System (ADS)

    Zheng, Jia-Jia; Li, Qiao-Zhi; Dang, Jing-Shuang; Wang, Wei-Wei; Zhao, Xiang

    2016-01-01

    Using spin-polarized density functional theory calculations, we performed theoretical investigations on the electronic and magnetic properties of transition metal embedded porphyrin-based nanowires (TM-PNWs, TM = Cr, Mn, Co, Ni, Cu, and Zn). Our results indicate that Ni-PNW and Zn-PNW are nonmagnetic while the rest species are magnetic, and the magnetic moments in TM-PNWs and their corresponding isolated monomer structures are found to be the same. In addition, the spin coupling in the magnetic nanowires can be ignored leading to their degenerate AFM and FM states. These results can be ascribed to the weak intermetallic interactions because of the relatively large distances between neighbor TM atoms. Among all TM-PNW structures considered here, only Mn-PNW shows a half-metallic property while the others are predicted to be semiconducting. The present work paves a new way of obtaining ferromagnetic porphyrin-based nanowires with TM atoms distributed separately and orderly, which are expected to be good candidates for catalysts, energy storage and molecular spintronics.

  18. Maintain rigid structures in Verlet based cartesian molecular dynamics simulations.

    PubMed

    Tao, Peng; Wu, Xiongwu; Brooks, Bernard R

    2012-10-07

    An algorithm is presented to maintain rigid structures in Verlet based cartesian molecular dynamics (MD) simulations. After each unconstrained MD step, the coordinates of selected particles are corrected to maintain rigid structures through an iterative procedure of rotation matrix computation. This algorithm, named as SHAPE and implemented in CHARMM program suite, avoids the calculations of Lagrange multipliers, so that the complexity of computation does not increase with the number of particles in a rigid structure. The implementation of this algorithm does not require significant modification of propagation integrator, and can be plugged into any cartesian based MD integration scheme. A unique feature of the SHAPE method is that it is interchangeable with SHAKE for any object that can be constrained as a rigid structure using multiple SHAKE constraints. Unlike SHAKE, the SHAPE method can be applied to large linear (with three or more centers) and planar (with four or more centers) rigid bodies. Numerical tests with four model systems including two proteins demonstrate that the accuracy and reliability of the SHAPE method are comparable to the SHAKE method, but with much more applicability and efficiency.

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

    PubMed

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

    2011-07-01

    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 and pixel-level (rather than cell-based) quantification methods. 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, estrogen 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. 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 their 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. © 2011 Blackwell Publishing Limited.

  20. 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

  1. Magnetic and electronic properties of porphyrin-based molecular nanowires

    SciTech Connect

    Zheng, Jia-Jia; Li, Qiao-Zhi; Dang, Jing-Shuang; Zhao, Xiang; Wang, Wei-Wei

    2016-01-15

    Using spin-polarized density functional theory calculations, we performed theoretical investigations on the electronic and magnetic properties of transition metal embedded porphyrin-based nanowires (TM-PNWs, TM = Cr, Mn, Co, Ni, Cu, and Zn). Our results indicate that Ni-PNW and Zn-PNW are nonmagnetic while the rest species are magnetic, and the magnetic moments in TM-PNWs and their corresponding isolated monomer structures are found to be the same. In addition, the spin coupling in the magnetic nanowires can be ignored leading to their degenerate AFM and FM states. These results can be ascribed to the weak intermetallic interactions because of the relatively large distances between neighbor TM atoms. Among all TM-PNW structures considered here, only Mn-PNW shows a half-metallic property while the others are predicted to be semiconducting. The present work paves a new way of obtaining ferromagnetic porphyrin-based nanowires with TM atoms distributed separately and orderly, which are expected to be good candidates for catalysts, energy storage and molecular spintronics.

  2. Ultrafast molecular orbital imaging based on attosecond photoelectron diffraction.

    PubMed

    Li, Yang; Qin, Meiyan; Zhu, Xiaosong; Zhang, Qingbin; Lan, Pengfei; Lu, Peixiang

    2015-04-20

    We present ab initio numerical study of ultrafast ionization dynamics of H(2)(+) as well as CO(2) and N(2) exposed to linearly polarized attosecond extreme ultraviolet pulses. When the molecules are aligned perpendicular to laser polarization direction, photonionization of these molecules show clear and distinguishing diffraction patterns in molecular attosecond photoelectron momentum distributions. The internuclear distances of the molecules are related to the position of the associated diffraction patterns, which can be determined with high accuracy. Moreover, the relative heights of the diffraction fringes contain fruitful information of the molecular orbital structures. We show that the diffraction spectra can be well produced using the two-center interference model. By adopting a simple inversion algorithm which takes into account the symmetry of the initial molecular orbital, we can retrieve the molecular orbital from which the electron is ionized. Our results offer possibility for imaging of molecular structure and orbitals by performing molecular attosecond photoelectron diffraction.

  3. Structural distortions in molecular-based quantum cellular automata: a minimal model based study.

    PubMed

    Bonilla, Alejandro Santana; Gutierrez, Rafael; Sandonas, Leonardo Medrano; Nozaki, Daijiro; Bramanti, Alessandro Paolo; Cuniberti, Gianaurelio

    2014-09-07

    Molecular-based quantum cellular automata (m-QCA), as an extension of quantum-dot QCAs, offer a novel alternative in which binary information can be encoded in the molecular charge configuration of a cell and propagated via nearest-neighbor Coulombic cell-cell interactions. Appropriate functionality of m-QCAs involves a complex relationship between quantum mechanical effects, such as electron transfer processes within the molecular building blocks, and electrostatic interactions between cells. The influence of structural distortions of single m-QCA are addressed in this paper within a minimal model using an diabatic-to-adiabatic transformation. We show that even small changes of the classical square geometry between driver and target cells, such as those induced by distance variations or shape distortions, can make cells respond to interactions in a far less symmetric fashion, modifying and potentially impairing the expected computational behavior of the m-QCA.

  4. Generalized Molecular Descriptors Derived From Event-Based Discrete Derivative.

    PubMed

    Martínez-Santiago, Oscar; Cabrera, Reisel Millán; Marrero-Ponce, Yovani; Barigye, Stephen J; Le-Thi-Thu, Huong; Torres, F Javier; Zambrano, Cesar H; Yaber-Goenaga, Ivan; Cruz-Monteagudo, Maykel; López, Yoan Martínez; Giménez, Facundo Pérez; Torrens, Francisco

    2016-01-01

    In the present study, a generalized approach for molecular structure characterization is introduced, based on the relation frequency matrix (F) representation of the molecular graph and the subsequent calculation of the corresponding discrete derivative (finite difference) over a pair of elements (atoms). In earlier publications (22- 24), an unique event, named connected subgraphs, (based on the Kier-Hall's subgraphs) was systematically employed for the computation of the matrix F. The present report is a generalization of this notion, in which eleven additional events are introduced, classified in three categories, namely, topological (terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sach's subgraphs), fingerprints (MACCs, E-state and substructure fingerprints) and atomic contributions (Ghose and Crippen atom-types for hydrophobicity and refractivity) for F generation. The events are intended to capture diverse information by the generation or search of different kinds of substructures from the graph representation of a molecule. The discrete derivative over duplex atom relations are calculated for each event, and the resulting derivatives, local vertex invariants (LOVIs) are finally obtained. These LOVIs are subsequently employed as the basis for the calculation of global and local indices over groups of atoms (heteroatoms, halogens, methyl carbons, etc.), by using norms, means, statistics and classical algorithms as aggregator (fusion) operators. These indices were implemented in our house software DIVATI (Derivative Type Indices, a new module of TOMOCOMDCARDD system). DIVATI provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http: //www.tomocomd.com. Factor analysis shows that the presented events are rather orthogonal and collect diverse information about the chemical structure. Finally, QSPR models were built to describe the logP and logK of 34

  5. Ridge-based bias potentials to accelerate molecular dynamics

    NASA Astrophysics Data System (ADS)

    Xiao, Penghao; Duncan, Juliana; Zhang, Liang; Henkelman, Graeme

    2015-12-01

    An effective way to accelerate rare events in molecular dynamics simulations is to apply a bias potential which destabilizes minima without biasing the transitions between stable states. This approach, called hyperdynamics, is limited by our ability to construct general bias potentials without having to understand the reaction mechanisms available to the system, a priori. Current bias potentials are typically constructed in terms of a metric which quantifies the distance that a trajectory deviates from the reactant state minimum. Such metrics include detection of negative curvatures of the potential, an energy increase, or deviations in bond lengths from the minimum. When one of these properties exceeds a critical value, the bias potentials are constructed to approach zero. A problem common to each of these schemes is that their effectiveness decreases rapidly with system size. We attribute this problem to a diminishing volume defined by the metrics around a reactant minimum as compared to the total volume of the reactant state basin. In this work, we mitigate the dimensionality scaling problem by constructing bias potentials that are based upon the distance to the boundary of the reactant basin. This distance is quantified in two ways: (i) by following the minimum mode direction to the reactant boundary and (ii) by training a machine learning algorithm to give an analytic expression for the boundary to which the distance can be calculated. Both of these ridge-based bias potentials are demonstrated to scale qualitatively better with dimensionality than the existing methods. We attribute this improvement to a greater filling fraction of the reactant state using the ridge-based bias potentials as compared to the standard potentials.

  6. 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.

  7. Molecular imaging biomarkers for cell-based immunotherapies.

    PubMed

    Haris, Mohammad; Bagga, Puneet; Hariharan, Hari; McGettigan-Croce, Bevin; Johnson, Laura A; Reddy, Ravinder

    2017-06-19

    While many decades of scientific research studies have gone into harnessing the power of the immune system to fight cancer, only recently have cancer immunotherapeutic approaches begun to show robust clinical responses in patients with a variety of cancers. These treatments are adding to the current arsenal of cancer treatments; surgery, radiation and chemotherapy, and increasing the therapeutic options for cancer patients. Despite these advances, issues associated with these therapies include that not all patients respond to these therapies, and some patients who respond experience varying degrees of toxicities. One of the major issues affecting immunotherapy is the inability to evaluate trafficking of activated T-cells into sites of tumor. The current diagnostic imaging based on conventional anatomic imaging, which is the mainstay to monitor response to cytotoxic chemotherapy or radiation, is not adequate to assess initial response to immunotherapy or disease evolution. Patients' prognosis by histological analysis has limited use in regards to immunotherapy. Thus, there is a crucial need for noninvasive biomarkers for screening patients that show long term response to therapy. Here, we provide a brief account of emerging molecular magnetic resonance imaging biomarkers that have potential to exploit the metabolism and metabolic products of activated T cells.

  8. 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.

  9. 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.

  10. 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.

  11. 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

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

    PubMed

    Mingarro, I; Abad, C; Braco, L

    1995-04-11

    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.

  13. Molecular pincers: antibody-based homogeneous protein sensors.

    PubMed

    Heyduk, Ewa; Dummit, Benjamin; Chang, Yie-Hwa; Heyduk, Tomasz

    2008-07-01

    We describe here a new homogeneous antibody-based protein sensor design (molecular pincers) that allows rapid and sensitive detection of a specific protein in solution. In the presence of the target protein these sensors produce fluorescence signal derived from target-dependent annealing of short complementary fluorochrome-labeled oligonucleotides attached to a pair of target-specific antibodies via nanometer-scale flexible linkers. The sensors allow near-instantaneous detection of the target with sensitivity and specificity approaching that of enzyme-linked immunosorbent assay (ELISA) but requiring no sample manipulation other then the addition of the sample to the sensor mix. We used cardiac troponin I and C-reactive protein as the targets to validate these desirable properties of the sensors. Due to the availability of antibodies to thousands of interesting targets and the straightforward design blueprint of the sensors we expect their wide-ranging applications in research and medical diagnosis, especially when simplicity, high throughput, and short detection time are essential.

  14. 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.

  15. 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.

  16. Cryosurgery--a putative approach to molecular-based optimization.

    PubMed

    Baust, John G; Gage, Andrew A; Clarke, Dominic; Baust, John M; Van Buskirk, Robert

    2004-04-01

    Cryosurgery must be performed in a manner that produces a predictable response in an appropriate volume of tissue. In present-day clinical practice, that goal is not always achieved. Concerns with cryosurgical techniques in cancer therapy focus in part on the incidence of recurrent disease in the treated site, which is commonly approximately 20-40% in metastatic liver tumors, and prostate cancers. Whether the cause of this failure is disease-based or technique related, cryosurgery for cancer commonly needs the support of adjunctive therapy in the form of anti-cancer drugs or radiotherapy to increase the rate of cell death in the peripheral zone of the therapeutic lesion where cell survival is in balance for several days post-treatment. Recent evidence has identified a third mechanism of cell death associated with cryosurgery. This mechanism, apoptosis or gene regulated cell death, is additive with both the direct ice-related cell damage that occurs during the operative freeze-thaw intervals and coagulative necrosis that occurs over days post-treatment. In this manuscript we discuss, through a combination of literature review and new data, the combined roles of these distinct modes of cell death in a prostate and colorectal cancer. Data are presented suggesting that sub-freezing temperatures, when sequentially applied with low dose chemotherapy, may provide improved cancer cell death in the freeze zone periphery. Since the mechanism of action of most common chemotherapeutic agents is to initiate apoptosis in cancer cells, the observation that sub-freezing exposures yields a similar effect provides a possible route toward molecular-based procedural optimization to improve therapeutic outcome.

  17. MrGrid: A Portable Grid Based Molecular Replacement Pipeline

    PubMed Central

    Reboul, Cyril F.; Androulakis, Steve G.; Phan, Jennifer M. N.; Whisstock, James C.; Goscinski, Wojtek J.; Abramson, David; Buckle, Ashley M.

    2010-01-01

    Background The crystallographic determination of protein structures can be computationally demanding and for difficult cases can benefit from user-friendly interfaces to high-performance computing resources. Molecular replacement (MR) is a popular protein crystallographic technique that exploits the structural similarity between proteins that share some sequence similarity. But the need to trial permutations of search models, space group symmetries and other parameters makes MR time- and labour-intensive. However, MR calculations are embarrassingly parallel and thus ideally suited to distributed computing. In order to address this problem we have developed MrGrid, web-based software that allows multiple MR calculations to be executed across a grid of networked computers, allowing high-throughput MR. Methodology/Principal Findings MrGrid is a portable web based application written in Java/JSP and Ruby, and taking advantage of Apple Xgrid technology. Designed to interface with a user defined Xgrid resource the package manages the distribution of multiple MR runs to the available nodes on the Xgrid. We evaluated MrGrid using 10 different protein test cases on a network of 13 computers, and achieved an average speed up factor of 5.69. Conclusions MrGrid enables the user to retrieve and manage the results of tens to hundreds of MR calculations quickly and via a single web interface, as well as broadening the range of strategies that can be attempted. This high-throughput approach allows parameter sweeps to be performed in parallel, improving the chances of MR success. PMID:20386612

  18. Optical sensors based on the molecular condensation nuclei detector

    NASA Astrophysics Data System (ADS)

    Kuptsov, Vladimir D.; Katelevsky, Vadim Y.; Valyukhov, Vladimir P.

    2015-05-01

    Molecular condensation nuclei (MCN) detector is a specialized optical sensor which provides for monitoring of various chemicals impurity in the environment and diagnosis of diseases in human exhaled air ("electronic nose" biosensor). Structurally MCN detector is included in the highly sensitive gas analyzers based on MCN method. The article describes the fundamental principles, specific features and application fields of the advanced highly sensitive MCN method. The MCN method is based on the application of various physico-chemical processes to the flow of a gas containing impurities. As a result of these processes aerosol particle that are about 106 times larger than the original molecule of the impurity are produced. The ability of the aerosol particle to scatter incident light also increases ~1014÷1016 times compared with the original molecule and the aerosol particle with the molecule of the impurity in the center is easily detected by light scattering inside a photometer. By measuring of the light scattering intensity is determined concentration of chemical impurities in the air. Aerosol particles in the MCN detector are formed in the condensing devices through overgrowth of the molecule detectable impurity by molecules so-called «developer» substance. At the final stage of the analysis in the MCN detector is measured light scattering by aerosol particles which is proportional to the concentration of determined impurities in the environment. For calculations of the scattered radiation is applicable Mie's theory considering the scattering of light by spherical particles whose size is comparable to the wavelength of light. We have determined that the light scattering by aerosol particles is interferometric and is comparable within an order of magnitude with light scattering by the air inside a photometer. The detection threshold for the target component of the gas analyzer is attained at the spontaneous ionization background level and not at the limiting

  19. A modular hierarchy-based theory of the chemical origins of life based on molecular complementarity.

    PubMed

    Root-Bernstein, Robert

    2012-12-18

    Albert Szent-Gyorgyi once defined discovery as seeing what everyone else sees and thinking what no one else thinks. I often find that phenomena that are obvious to other people are not obvious to me. Molecular complementarity is one of these phenomena: while rare among any random set of compounds, it is ubiquitous in living systems. Because every molecule in a living system binds more or less specifically to several others, we now speak of "interactomes". What explains the ubiquity of molecular complementarity in living systems? What might such an explanation reveal about the chemical origins of life and the principles that have governed its evolution? Beyond this, what might complementarity tell us about the optimization of integrated systems in general? My research combines theoretical and experimental approaches to molecular complementarity relating to evolution from prebiotic chemical systems to superorganismal interactions. Experimentally, I have characterized complementarity involving specific binding between small molecules and explored how these small-molecule modules have been incorporated into macromolecular systems such as receptors and transporters. Several general principles have emerged from this research. Molecules that bind to each other almost always alter each other's physiological effects; and conversely, molecules that have antagonistic or synergistic physiological effects almost always bind to each other. This principle suggests a chemical link between biological structure and function. Secondly, modern biological systems contain an embedded molecular paleontology based on complementarity that can reveal their chemical origins. This molecular paleontology is often manifested through modules involving small, molecularly complementary subunits that are built into modern macromolecular structures such as receptors and transporters. A third principle is that complementary modules are conserved and repurposed at every stage of evolution. Molecular

  20. 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.

  1. Molecular mechanics modeling of azobenzene-based photoswitches.

    PubMed

    Duchstein, Patrick; Neiss, Christian; Görling, Andreas; Zahn, Dirk

    2012-06-01

    We present an extension of the generalized amber force field to allow the modeling of azobenzenes by means of classical molecular mechanics. TD-DFT calculations were employed to derive different interaction models for 4-hydroxy-4'-methyl-azobenzene, including the ground (S(0)) and S(1) excited state. For both states, partial charges and the -N = N- torsion potentials were characterized. On this basis, we pave the way to large-scale model simulations involving azobenzene molecular switches. Using the example of an isolated molecule, the mechanics of cyclic switching processes are demonstrated by classical molecular dynamics simulations.

  2. Prediction of molecular properties including symmetry from quantum-based molecular structural formulas, VIF.

    PubMed

    Alia, Joseph D; Vlaisavljevich, Bess; Abbot, Matthew; Warneke, Hallie; Mastin, Tyson

    2008-10-09

    Structurally covariant valency interaction formulas, VIF, gain chemical significance by comparison with resonance structures and natural bond orbital, NBO, bonding schemes and at the same time allow for additional prediction such as symmetry of ring systems and destabilization of electron pairs with respect to reference energy of -1/2 Eh. Comparisons are based on three chemical interpretations of Sinanoğlu's theory of structural covariance: (1) sets of structurally covariant quantum structural formulas, VIF, are interpreted as the same quantum operator represented in linearly related basis frames; (2) structurally covariant VIF pictures are interpreted as sets of molecular species with similar energy; and (3) the same VIF picture can be interpreted as different quantum operators, one-electron density or Hamiltonian; for example. According to these three interpretations, bond pair, lone pair, and free radical electrons understood in terms of a localized orbital representation are recognized as having energies above, below, or equal to a predetermined reference, frequently-1/2 Eh. The probable position of electron pairs and radical electrons is predicted. The selectivity of concerted ring closures in allyl anion and cation is described. Symmetries of conjugated ring systems are predicted according to their numbers of pi-electrons and spin-multiplicity. The pi-distortivity of benzene is predicted.The 3c/2e- H-bridging bonds in diborane are derived in a natural way according to the notion that the bridging bonds will have delocalizing interactions between them consistent with results of the NBO method. Key chemical bonding motifs are described using VIF. These include 2c/1e-, 2c/2e-, 2c/3e-, 3c/2e-, 3c/3e-,3c/4e-, 4n antiaromatic, and 4n+2 aromatic bonding systems. Some common organic functional groups are represented as VIF pictures and because these pictures can be interpreted simultaneously as one-electron density and Hamiltonian operators, the valence shell

  3. Thermoresponsive Polyphosphazene-Based Molecular Brushes by Living Cationic Polymerization

    PubMed Central

    Wilfert, Sandra; Iturmendi, Aitziber; Henke, Helena; Brüggemann, Oliver; Teasdale, Ian

    2014-01-01

    Summary A series of polyphosphazenes with molecular brush type structures have been prepared with controlled molecular weights and narrow polydispersities. The polymers show lower critical solution temperatures (LCST) between 18 and 90 °C, which can be easily tailored by choice of side-substituent to suit the required application. A temperature triggered self-assembly is observed to give stable colloidal aggregates with dimensions in the region of 100–300 nm. PMID:24926189

  4. Conformational Analysis in 18-Membered Macrolactones Based on Molecular Modeling

    PubMed Central

    Belaidi, Salah; Harkati, Dalal

    2011-01-01

    Conformational analysis of 18-ring membered macrolactones has been carried out using molecular mechanics calculations and molecular dynamics. A high conformational flexibility of macrolactones was obtained, and an important stereoselectivity was observed for the complexed macrolides. For 18d macrolactone, which was presented by a most favored conformer with 20.1% without complex, it was populated with 50.1% in presence of Fe(CO)3. PMID:24052826

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

    DTIC Science & Technology

    2015-01-01

    Molecular Dynamics Simula- tion of Hypergolic Reactions Between an Energetic Ionic Liquid and Nitric Acid, 57th JANNAF Joint Subcommittee Meet- ing...its high toxic vapor , there is a thrust towards developing low-toxic hypergolic fuels. Ultra-low vapor pressure ionic liquids are one such potential...understanding of the hypergolic nature of ionic liquids is far from clear. This work used the computed energy gap values between the highest occupied molecular

  6. Absorption classification of oral drugs based on molecular surface properties.

    PubMed

    Bergström, Christel A S; Strafford, Melissa; Lazorova, Lucia; Avdeef, Alex; Luthman, Kristina; Artursson, Per

    2003-02-13

    The aim of this study was to investigate whether easily calculated and comprehended molecular surface properties can predict drug solubility and permeability with sufficient accuracy to allow theoretical absorption classification of drug molecules. For this purpose, structurally diverse, orally administered model drugs were selected from the World Health Organization (WHO)'s list of essential drugs. The solubility and permeability of the drugs were determined using well-established in vitro methods in highly accurate experimental settings. Descriptors for molecular surface area were generated from low-energy conformations obtained by conformational analysis using molecular mechanics calculations. Correlations between the calculated molecular surface area descriptors, on one hand, and solubility and permeability, on the other, were established with multivariate data analysis (partial least squares projection to latent structures (PLS)) using training and test sets. The obtained models were challenged with external test sets. Both solubility and permeability of the druglike molecules could be predicted with high accuracy from the calculated molecular surface properties alone. The established correlations were used to perform a theoretical biopharmaceutical classification of the WHO-listed drugs into six classes, resulting in a correct prediction for 87% of the essential drugs. An external test set consisting of Food and Drug Administration (FDA) standard compounds for biopharmaceutical classification was predicted with 77% accuracy. We conclude that PLS models of easily comprehended molecular surface properties can be used to rapidly provide absorption profiles of druglike molecules early on in drug discovery.

  7. Physics-Based Visual Characterization of Molecular Interaction Forces.

    PubMed

    Hermosilla, Pedro; Estrada, Jorge; Guallar, Victor; Ropinski, Timo; Vinacua, Alvar; Vazquez, Pere-Pau

    2017-01-01

    Molecular simulations are used in many areas of biotechnology, such as drug design and enzyme engineering. Despite the development of automatic computational protocols, analysis of molecular interactions is still a major aspect where human comprehension and intuition are key to accelerate, analyze, and propose modifications to the molecule of interest. Most visualization algorithms help the users by providing an accurate depiction of the spatial arrangement: the atoms involved in inter-molecular contacts. There are few tools that provide visual information on the forces governing molecular docking. However, these tools, commonly restricted to close interaction between atoms, do not consider whole simulation paths, long-range distances and, importantly, do not provide visual cues for a quick and intuitive comprehension of the energy functions (modeling intermolecular interactions) involved. In this paper, we propose visualizations designed to enable the characterization of interaction forces by taking into account several relevant variables such as molecule-ligand distance and the energy function, which is essential to understand binding affinities. We put emphasis on mapping molecular docking paths obtained from Molecular Dynamics or Monte Carlo simulations, and provide time-dependent visualizations for different energy components and particle resolutions: atoms, groups or residues. The presented visualizations have the potential to support domain experts in a more efficient drug or enzyme design process.

  8. On the way to rotaxane-based molecular motors: studies in molecular mobility and topological chirality.

    PubMed

    Schalley, C A; Beizai, K; Vögtle, F

    2001-06-01

    ATP synthase represents a machine at the molecular level which couples the rotation of an axle in a wheel with the endergonic production of ATP, the general source of chemical energy in the cell. The natural system prototypically bears all features of a macroscopic motor: a rotor within a stator held by a membrane and fueled by a difference in chemical potential in the form of a proton gradient combined with a machine for ATP production. The assembly of axle and wheel to a rotor device reminds one very much of a rotaxane. In this Account, we discuss some important features of motors and their (potential) realization in simpler artificial model systems, that is, the molecular mobility of mechanically bound molecules, the importance of chirality for unidirectional motion, the sources of energy for driving the rotation, and the potential of using membranes and surfaces for ordering a large number of devices to achieve macroscopic effects.

  9. Molecularly based management of gliomas in clinical practice.

    PubMed

    Rudà, Roberta; Pellerino, Alessia; Magistrello, Michela; Franchino, Federica; Pinessi, Lorenzo; Soffietti, Riccardo

    2015-09-01

    Histological subtyping and grading of malignancy are the cornerstone of the present World Health Organization (WHO) Classification of CNS tumors. However, among diffuse gliomas of the adult, patients with histologically identical tumors may have different outcomes. As the genomic analysis of these tumors has progressed, it has become clear that specific molecular features transcend histologically defined variants, and may become markers of prognostic and/or predictive value. At the present time, the number of molecular biomarkers with confirmed clinical relevance (MGMT promoter methylation, 1p/19q codeletion, IDH1/2 mutations) remains limited, but new technologies will hopefully provide new candidates requiring rigorous validation in well-designed clinical trials.

  10. Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

    PubMed Central

    Mense, Martin; Fischman, Sharon; Shitrit, Alina; Bihler, Hermann; Ben-Zeev, Efrat; Schutz, Nili; Pedemonte, Nicoletta; Thomas, Philip J.; Bridges, Robert J.; Wetmore, Diana R.; Marantz, Yael; Senderowitz, Hanoch

    2014-01-01

    Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability. In silico structure-based screening was performed at the putative binding-sites and a total of 496 candidate compounds from all three sites were tested in functional assays. A total of 15 compounds, representing diverse chemotypes, were identified as F508del folding correctors. This corresponds to a 3% hit rate, ∼tenfold higher than hit rates obtained in corresponding high-throughput screening campaigns. The same binding sites also yielded potentiators and, most notably, compounds with a dual corrector-potentiator activity (dual-acting). Compounds harboring both activity types may prove to be better leads for the development of CF therapeutics than either pure correctors or pure potentiators. To the best of our knowledge this is the first report of structure-based discovery of CFTR modulators. PMID:20976528

  11. Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

    NASA Astrophysics Data System (ADS)

    Kalid, Ori; Mense, Martin; Fischman, Sharon; Shitrit, Alina; Bihler, Hermann; Ben-Zeev, Efrat; Schutz, Nili; Pedemonte, Nicoletta; Thomas, Philip J.; Bridges, Robert J.; Wetmore, Diana R.; Marantz, Yael; Senderowitz, Hanoch

    2010-12-01

    Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability. In silico structure-based screening was performed at the putative binding-sites and a total of 496 candidate compounds from all three sites were tested in functional assays. A total of 15 compounds, representing diverse chemotypes, were identified as F508del folding correctors. This corresponds to a 3% hit rate, tenfold higher than hit rates obtained in corresponding high-throughput screening campaigns. The same binding sites also yielded potentiators and, most notably, compounds with a dual corrector-potentiator activity (dual-acting). Compounds harboring both activity types may prove to be better leads for the development of CF therapeutics than either pure correctors or pure potentiators. To the best of our knowledge this is the first report of structure-based discovery of CFTR modulators.

  12. 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

  13. Molecular recognition-based detoxification of aluminum in human plasma.

    PubMed

    Demircelik, Ahmet H; Andac, Muge; Andac, Cenk A; Say, Ridvan; Denizli, Adil

    2009-01-01

    Molecular recognition-based Al(3+)-imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-L-glutamic acid) (PHEMAGA-Al(3+)) beads were prepared to be used in selective removal of Al(3+) out of human plasma overdosed with Al(3+) cations. The PHEMAGA-Al(3+) beads were synthesized by suspension polymerization in the presence of a template-monomer complex (MAGA-Al(3+)). The specific surface area of PHEMAGA-Al(3+) beads was found to be 55.6 m(2)/g on the average. The MAGA content in the PHEMAGA-Al(3+) beads were found to be 640 micgomol/g polymer. The template Al(3+) cations could be reversibly detached from the matrix to form PHEMAGA-Al(3+) using a 50 mM solution of EDTA. The Al(3+)-free PHEMAGA-Al(3+) beads were then exposed to a selective separation procedure of Al(3+) out of human plasma, which was implemented in a continuous system by packing the beads into a separation column (10 cm long with an inner diameter of 0.9 cm) equipped with a water jacket to control the temperature. The Al(3+) adsorption capacity of the PHEMAGA-Al(3+) beads decreased drastically from 0.76 mg/g polymer to 0.22 mg/g polymer as the flow rate was increased from 0.3 ml/min to 1.5 ml/min. The relative selectivity coefficients of the PHEMAGA-Al(3+) beads for Al(3+)/Fe(3+), Al(3+)/Cu(2+) and Al(3+)/Zn(2+) were found to be 4.49, 8.95 and 32.44 times greater than those of the non-imprinted PHEMAGA beads, respectively. FT-IR analyses on the synthesized PHEMAGA-Al(3+) beads reveals monodentate and bidentate binding modes of Al(3+) in complex with the carboxylate groups of the glutamate residues. Density functional theory computations at the B3LYP/6-31G(d,p) basis set suggests that structured water molecules play essential role in the stability of the monodentate binding mode in 1:1 PHEMAGA-Al(3+) complexes. The PHEMAGA-Al(3+) beads were recovered and reused many times, with no significant decrease in their adsorption capacities.

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

    PubMed

    Donadieu, Jean; Fenneteau, Odile; Beaupain, Blandine; Mahlaoui, Nizar; Chantelot, Christine Bellanné

    2011-05-19

    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-hematopoietic 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

  15. 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.

  16. Molecular filter-based diagnostics in high speed flows

    NASA Technical Reports Server (NTRS)

    Elliott, Gregory S.; Samimy, MO; Arnette, Stephen A.

    1993-01-01

    The use of iodine molecular filters in nonintrusive planar velocimetry methods is examined. Detailed absorption profiles are obtained to highlight the effects that determine the profile shape. It is shown that pressure broadening induced by the presence of a nonabsorbing vapor can be utilized to significantly change the slopes bounding the absorbing region while remaining in the optically-thick regime.

  17. 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…

  18. 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)

  19. Engineering controllable bidirectional molecular motors based on myosin.

    PubMed

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

    2012-02-19

    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.

  20. Molecular bases and improvement of heat tolerance in crop plants

    USDA-ARS?s Scientific Manuscript database

    High temperature is a major constraint to crop productivity, causing substantial reductions in yield and quality, and expected to become a more devastating factor due to global warming. A better understanding of molecular mechanisms of tolerance to high temperatures is necessary for designing and de...

  1. 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)

  2. 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.

  3. 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.

  4. 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.

  5. An electrochemical sensor for phenylephrine based on molecular imprinting.

    PubMed

    Yao, Liuduan; Tang, Youwen; Zeng, Weipeng; Huang, Zhaofa

    2009-09-01

    Molecularly imprinted polymers (MIPs) were applied as molecular recognition elements to an electrochemical sensor for phenylephrine. A MIPs membrane was created on a glassy carbon electrode. SEM revealed a gradual change on the morphology of modified electrodes as the ratios of function monomer and cross-linking varied. When the ratio was 4:40, the surface morphology between the imprinted electrode (M-electrode) and the control electrode (N-electrode) became unambiguously different. This artificial receptor exhibited high selectivity for the template compared to closely related analogue. The response of the sensor varied in different concentration range might due to the heterogeneity of the MIPs membrane. This sensor was also used to determine phenylephrine in tablet samples.

  6. [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.

  7. 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

  8. 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.

  9. Web-based cheminformatics and molecular property prediction tools supporting drug design and development at Novartis.

    PubMed

    Ertl, P; Mühlbacher, J; Rohde, B; Selzer, P

    2003-01-01

    Web-based tools offer many advantages for processing chemical information, most notably ease of use and high interactivity. Therefore more and more pharmaceutical companies are using web technology to deliver sophisticated molecular processing tools directly to the desks of their chemists, to assist them in the process of designing and developing new drugs. In this paper, the web-based cheminformatics system developed at Novartis and currently used by more than thousand users is described. The system allows various molecular modeling and molecular processing tasks, including the calculation of molecular and substituent properties, property-based virtual screening, visualization of molecules, bioisosteric design, diversity analysis, and support of combinatorial chemistry. The methodology to calculate various molecular properties relevant to drug design is described, including the prediction of intestinal absorption, blood-brain barrier penetration, efflux, and water solubility. Information about the web technology used is also provided.

  10. Comprehensive characterization of molecular interactions based on nanomechanics.

    PubMed

    Ghatkesar, Murali Krishna; Lang, Hans-Peter; Gerber, Christoph; Hegner, Martin; Braun, Thomas

    2008-01-01

    Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions.

  11. Comprehensive Characterization of Molecular Interactions Based on Nanomechanics

    PubMed Central

    Lang, Hans-Peter; Gerber, Christoph; Hegner, Martin

    2008-01-01

    Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (∼748*106 Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions. PMID:18978938

  12. 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.

  13. 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.

  14. Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer.

    PubMed

    Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martínez, José Manuel; de la Vieja, Antonio; García-Jiménez, Custodia

    2017-02-01

    The association between diabetes and cancer was hypothesized almost one century ago. Today, a vast number of epidemiological studies support that obese and diabetic populations are more likely to experience tissue-specific cancers, but the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer share many hormonal, immune, and metabolic changes that may account for the relationship between diabetes and cancer. In addition, antidiabetic treatments may have an impact on the occurrence and course of some cancers. Moreover, some anticancer treatments may induce diabetes. These observations aroused a great controversy because of the ethical implications and the associated commercial interests. We report an epidemiological update from a mechanistic perspective that suggests the existence of many common and differential individual mechanisms linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The challenge today is to identify the molecular links responsible for this association. Classification of cancers by their molecular signatures may facilitate future mechanistic and epidemiological studies. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Estudio fotométrico de emisiones moleculares del cometa Halley en la etapa de post-perihelio.

    NASA Astrophysics Data System (ADS)

    Sisteró, R. F.; Clariá, J. J.; Lapasset, E.

    Results from photoelectric photometry in molecular bands of comet Halley carried out at Bosque Alegre are presented. The largest emissions measured are those of molecules of C2, CN and C3 respectively.

  16. 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.

  17. 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…

  18. 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…

  19. Molecular Imaging: A Useful Tool for the Development of Natural Killer Cell-Based Immunotherapies.

    PubMed

    Gangadaran, Prakash; Ahn, Byeong-Cheol

    2017-01-01

    Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK) cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.

  20. Syntheses of steroid-based molecularly imprinted polymers and their molecular recognition study with spectrometric detection

    NASA Astrophysics Data System (ADS)

    Dong, He; Tong, Ai-jun; Li, Long-di

    2003-01-01

    Recognition of five steroid compounds, β-estradiol, ethynylestradiol, estradiolbenzoate, testosterone and methyltestosterone were studied using a synthesized molecularly imprinted polymer (MIP). When β-estradiol was used as the template molecule, the polymer was synthesized with methacrylic acid (MAA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross linking agent through non-covalent interactions. It is found that the kind of porogen solvent and the polymerization conditions greatly affected the binding ability of a MIP to a certain molecule. Releasing of the template was performed by continuous extraction with methanol containing 10% acetic acid in a Soxhlet extractor. Our results indicated that such carefully synthesized MIP showed specific affinity toward β-estradiol in the adsorption process.

  1. Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

    PubMed Central

    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. PMID:24244318

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

    PubMed

    Tachikawa, Hiroto; Kawabata, Hiroshi

    2016-03-10

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

  3. Molecular nanostamp based on one-dimensional porphyrin polymers.

    PubMed

    Kanaizuka, Katsuhiko; Izumi, Atsushi; Ishizaki, Manabu; Kon, Hiroki; Togashi, Takanari; Miyake, Ryosuke; Ishida, Takao; Tamura, Ryo; Haga, Masa-aki; Moritani, Youji; Sakamoto, Masatomi; Kurihara, Masato

    2013-08-14

    Surface design with unique functional molecules by a convenient one-pot treatment is an attractive project for the creation of smart molecular devices. We have employed a silane coupling reaction of porphyrin derivatives that form one-dimensional polymer wires on substrates. Our simple one-pot treatment of a substrate with porphyrin has successfully achieved the construction of nanoscale bamboo shoot structures. The nanoscale bamboo shoots on the substrates were characterized by atomic force microscopy (AFM), UV-vis spectra, and X-ray diffraction (XRD) measurements. The uneven and rigid nanoscale structure has been used as a stamp for constructing bamboo shoot structures of fullerene.

  4. Molecular design of porphyrin-based nonlinear optical materials.

    PubMed

    Keinan, Shahar; Therien, Michael J; Beratan, David N; Yang, Weitao

    2008-11-27

    Nonlinear optical chromophores containing (porphyrinato)Zn(II), proquinoid, and (terpyridyl)metal(II) building blocks were optimized in a library containing approximately 10(6) structures using the linear combination of atomic potentials (LCAP) methodology. We report here the library design and molecular property optimizations. Two basic structural types of large beta(0) chromophores were examined: linear and T-shaped motifs. These T-shaped geometries suggest a promising NLO chromophoric architecture for experimental investigation and further support the value of performing LCAP searches in large chemical spaces.

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

    PubMed

    Fang, Tao; Jia, Junteng; Li, Shuhua

    2016-05-05

    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.

  6. Fragment Molecular Orbital method-based Molecular Dynamics (FMO-MD) as a simulator for chemical reactions in explicit solvation.

    PubMed

    Komeiji, Yuto; Ishikawa, Takeshi; Mochizuki, Yuji; Yamataka, Hiroshi; Nakano, Tatsuya

    2009-01-15

    Fragment Molecular Orbital based-Molecular Dynamics (FMO-MD, Komeiji et al., Chem Phys Lett 2003, 372, 342) is an ab initio MD method suitable for large molecular systems. Here, FMO-MD was implemented to conduct full quantum simulations of chemical reactions in explicit solvation. Several FMO-MD simulations were performed for a sphere of water to find a suitable simulation protocol. It was found that annealing of the initial configuration by a classical MD brought the subsequent FMO-MD trajectory to faster stabilization, and also that use of bond constraint in the FMO-MD heating stage effectively reduced the computation time. Then, the blue moon ensemble method (Sprik and Ciccotti, J Chem Phys 1998, 109, 7737) was implemented and was tested by calculating free energy profiles of the Menschutkin reaction (H3N + CH3Cl --> +H3NCH3 + Cl-) in the presence and absence of the solvent water via FMO-MD. The obtained free energy profiles were consistent with the Hammond postulate in that stabilization of the product by the solvent, namely hydration of Cl-, shifted the transition state to the reactant-side. Based on these FMO-MD results, plans for further improvement of the method are discussed. Copyright 2008 Wiley Periodicals, Inc.

  7. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Molecular Skin Surface-Based Transformation Visualization between Biological Macromolecules

    PubMed Central

    Cheng, Holun; Huang, Jing; Gao, Zhigang

    2017-01-01

    Molecular skin surface (MSS), proposed by Edelsbrunner, is a C2 continuous smooth surface modeling approach of biological macromolecules. Compared to the traditional methods of molecular surface representations (e.g., the solvent exclusive surface), MSS has distinctive advantages including having no self-intersection and being decomposable and transformable. For further promoting MSS to the field of bioinformatics, transformation between different MSS representations mimicking the macromolecular dynamics is demanded. The transformation process helps biologists understand the macromolecular dynamics processes visually in the atomic level, which is important in studying the protein structures and binding sites for optimizing drug design. However, modeling the transformation between different MSSs suffers from high computational cost while the traditional approaches reconstruct every intermediate MSS from respective intermediate union of balls. In this study, we propose a novel computational framework named general MSS transformation framework (GMSSTF) between two MSSs without the assistance of union of balls. To evaluate the effectiveness of GMSSTF, we applied it on a popular public database PDB (Protein Data Bank) and compared the existing MSS algorithms with and without GMSSTF. The simulation results show that the proposed GMSSTF effectively improves the computational efficiency and is potentially useful for macromolecular dynamic simulations.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Peptide-Based Molecular Hydrogels as Supramolecular Protein Mimics.

    PubMed

    Singh, Nishant; Kumar, Mohit; Miravet, Juan F; Ulijn, Rein V; Escuder, Beatriu

    2017-01-23

    This Minireview concerns recent advances in the design, synthesis, and application of low molecular-weight peptidic hydrogelators. The sequence-specific combinations of amino acid side chain functionalities combined with hydrogen bonding of amide backbones and hydrophobic (aromatic) capping groups give these peptidic molecules the intrinsic tendency to self-assemble. The most prevalent designs include N-capped amino acid residues, bolamphiphilic peptides, and amphipathic peptides. Factors such as hydrophobic effects, the Hofmeister effect, and tunable ionization influence their aggregation properties. The self-assembly of simple bio-inspired building blocks into higher organized structures allows comparisons to be drawn with proteins and their complex functionalities, providing preliminary insights into complex biological functions and also enabling their application in a wide range of fields including catalysis, biomedical applications, and mimicry of natural dissipative systems. The Minireview is concluded by a short summary and outlook, highlighting the advances and steps required to bridge the gaps in the understanding of such systems.

  14. ChemPreview: an augmented reality-based molecular interface.

    PubMed

    Zheng, Min; Waller, Mark P

    2017-05-01

    Human computer interfaces make computational science more comprehensible and impactful. Complex 3D structures such as proteins or DNA are magnified by digital representations and displayed on two-dimensional monitors. Augmented reality has recently opened another door to access the virtual three-dimensional world. Herein, we present an augmented reality application called ChemPreview with the potential to manipulate bio-molecular structures at an atomistic level. ChemPreview is available at https://github.com/wallerlab/chem-preview/releases, and is built on top of the Meta 1 platform https://www.metavision.com/. ChemPreview can be used to interact with a protein in an intuitive way using natural hand gestures, thereby making it appealing to computational chemists or structural biologists. The ability to manipulate atoms in real world could eventually provide new and more efficient ways of extracting structural knowledge, or designing new molecules in silico. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Molecular modeling-based antioxidant arylidene barbiturates as urease inhibitors.

    PubMed

    Khan, Khalid Mohammed; Ali, Muhammad; Wadood, Abdul; Zaheer-ul-Haq; Khan, Momin; Lodhi, Muhammad Arif; Perveen, Shahnaz; Choudhary, Muhammad Iqbal; Voelter, Wolfgang

    2011-09-01

    Previously we have reported arylidene barbiturates 1-18 as a novel class of antioxidants; however, their urease inhibitory potential has not yet been explored. In this communication, molecular docking studies were used to predict the potential ligands from compounds 1-18 which culminated in the identification of certain new urease inhibitors. Ligands were screened in vitro for their urease inhibitory potential. Compound 1, as deduced from modeling studies, was found to be the most active urease inhibitor (13.0 ± 1.2 μM), when compared with the standard thiourea (IC₅₀=21.1 ± 0.3 μM). All of the compounds were found to be nontoxic to Artemia salina in brine shrimp lethality bioassay. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    PubMed

    de Boer, Hugo J; Thulin, Mats

    2012-01-01

    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.

  17. Molecular Bases of cyclodextrin Adapter Interactions with Engineered Protein Nanopores

    SciTech Connect

    Banerjee, A.; Mikhailova, E; Cheley, S; Gu, L; Montoya, M; Nagaoka, Y; Gouaux, E; Bayley, H

    2010-01-01

    Engineered protein pores have several potential applications in biotechnology: as sensor elements in stochastic detection and ultrarapid DNA sequencing, as nanoreactors to observe single-molecule chemistry, and in the construction of nano- and micro-devices. One important class of pores contains molecular adapters, which provide internal binding sites for small molecules. Mutants of the {alpha}-hemolysin ({alpha}HL) pore that bind the adapter {beta}-cyclodextrin ({beta}CD) {approx}10{sup 4} times more tightly than the wild type have been obtained. We now use single-channel electrical recording, protein engineering including unnatural amino acid mutagenesis, and high-resolution x-ray crystallography to provide definitive structural information on these engineered protein nanopores in unparalleled detail.

  18. 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

  19. 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

  20. 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.

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

    PubMed

    Garzón-Martínez, Gina A; Osorio-Guarín, Jaime A; Delgadillo-Durán, Paola; Mayorga, Franklin; Enciso-Rodríguez, Felix E; Landsman, David; Mariño-Ramírez, Leonardo; Barrero, Luz Stella

    2015-12-01

    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.

  2. 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

  3. 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.

  4. Ab initio study on (CO2)n clusters via electrostatics- and molecular tailoring-based algorithm

    NASA Astrophysics Data System (ADS)

    Jovan Jose, K. V.; Gadre, Shridhar R.

    An algorithm based on molecular electrostatic potential (MESP) and molecular tailoring approach (MTA) for building energetically favorable molecular clusters is presented. This algorithm is tested on prototype (CO2)n clusters with n = 13, 20, and 25 to explore their structure, energetics, and properties. The most stable clusters in this series are seen to show more number of triangular motifs. Many-body energy decomposition analysis performed on the most stable clusters reveals that the 2-body is the major contributor (>96%) to the total interaction energy. Vibrational frequencies and molecular electrostatic potentials are also evaluated for these large clusters through MTA. The MTA-based MESPs of these clusters show a remarkably good agreement with the corresponding actual ones. The most intense MTA-based normal mode frequencies are in fair agreement with the actual ones for smaller clusters. These calculated asymmetric stretching frequencies are blue-shifted with reference to the CO2 monomer.

  5. Long-term Changes in del 13C in DOC-based Benthic Food Webs in Arctic Lakes

    NASA Astrophysics Data System (ADS)

    Hershey, A. E.; O'Brien, W. J.; Fortino, K.; Keyse, M. D.; Binkley, E.; Lienesch, P. W.; McDonald, M. E.; Luecke, C.; Whalen, S.

    2005-05-01

    Arctic regions are rapidly warming, resulting in warmer summer lake temperatures and increased slumping of organic soils. In Lake NE-12, del 13C of primarily benthivorous lake trout has declined over eleven years. Two important lake trout prey, the caddisfly Grensia and the snail Lymnaea, also became more 13C-depleted. In Lake E-1, the deposit-feeding chironomid, Stictochironomus, also shifted toward lower del 13C, while filter-feeding Tanytarsini did not. Pelagic zooplankton did not show a trend toward 13C depletion overall, but were less consistent. Recent and concurrent studies have shown that DOC is an important resource for the benthic foodweb. Methanotrophy is part of the DOC-based foodweb. Our recent studies have shown that macrobenthos use some methanotroph production. Methane has very low del 13C, thus incorporation of a small amount of methane-based production has a large effect on del 13C. We suggest that climate-driven changes in the carbon pools available to microbes are resulting in increased importance of methanotrophs in macroinvertebrate diets, contributing to the observed long-term del 13C changes. Increased algal fractionation could also be important, but this mechanism has less support because zooplankton and filter-feeding chironomids did not show the same pattern, and previous studies have shown very limited benthic-pelagic coupling.

  6. Molecular cloning of the 8000-base thyroglobulin structural gene.

    PubMed

    Christophe, D; Mercken, L; Brocas, H; Pohl, V; Vassart, G

    1982-03-01

    Bovine thyroglobulin mRNA was reverse-transcribed into full-length double-stranded cDNA. The existence of three HindIII restriction endonuclease sites in the 8000-base thyroglobulin structural gene had allowed the easy cloning of the two internal HindIII fragments [Christophe et al. (1980) Eur. J. Biochem. 111, 419-423]. In the present study, the central portion of the structural gene was cloned in Escherichia coli as two individual recombinant plasmids containing 2000-base-pair and 4700-base-pair segments located respectively 5' and 3' relative to the unique BamHI site of the cDNA. BamHI linkers were added to the double-stranded cDNA and, following restriction with HindIII, selective cloning of the 5' (2600-base-pair) and 3' (1000-base-pair) terminal HindIII fragments was achieved by inserting them between the HindIII and BamHI sites of the plasmid pBR322. Partial sequencing of the 1000-base-pair 3'-terminal fragment demonstrated the presence of an A-A-U-A-A-A sequence in the mRNA 14 bases upstream from a poly(A) tract corresponding to the 3' end of the mRNA. Together, the four clones represent about 99% of the thyroglobulin structural gene and provide the starting material for the determination of thyroglobulin primary structure.

  7. The molecular bases of Alzheimer's disease and other neurodegenerative disorders.

    PubMed

    Maccioni, R B; Muñoz, J P; Barbeito, L

    2001-01-01

    Alzheimer's disease, the cause of one of the most common types of dementia, is a brain disorder affecting the elderly and is characterized by the formation of two main protein aggregates: senile plaques and neurofibrillary tangles, which are involved in the process leading to progressive neuronal degeneration and death. Neurodegeneration in Alzheimer's disease is a pathologic condition of cells rather than an accelerated way of aging. The senile plaques are generated by a deposition in the human brain of fibrils of the beta-amyloid peptide (Abeta), a fragment derived from the proteolytic processing of the amyloid precursor protein (APP). Tau protein is the major component of paired helical filaments (PHFs), which form a compact filamentous network described as neurofibrillary tangles (NFTs). Experiments with hippocampal cells in culture have indicated a relationship between fibrillary amyloid and the cascade of molecular signals that trigger tau hyperphosphorylations. Two main protein kinases have been shown to be involved in anomalous tau phosphorylations: the cyclin-dependent kinase Cdk5 and glycogen synthase kinase GSK3beta. Cdk5 plays a critical role in brain development and is associated with neurogenesis as revealed by studies in brain cells in culture and neuroblastoma cells. Deregulation of this protein kinase as induced by extracellular amyloid loading results in tau hyperphosphorylations, thus triggering a sequence of molecular events that lead to neuronal degeneration. Inhibitors of Cdk5 and GSK3beta and antisense oligonucleotides exert protection against neuronal death. On the other hand, there is cumulative evidence from studies in cultured brain cells and on brains that oxidative stress constitutes a main factor in the modification of normal signaling pathways in neuronal cells, leading to biochemical and structural abnormalities and neurodegeneration as related to the pathogenesis of Alzheimer's disease. This review is focused on the main protein

  8. 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

  9. Electrochemical sensors based on magnetic molecularly imprinted polymers: A review.

    PubMed

    Yáñez-Sedeño, Paloma; Campuzano, Susana; Pingarrón, José M

    2017-04-01

    Participation of magnetic component in molecularly imprinted polymers (MIPs) has facilitated enormously the incorporation of these polymeric materials on electrode surfaces allowing the design of electrochemical sensors with very attractive analytical characteristics in terms of simplicity, reproducibility, low fabrication cost, high sensitivity and selectivity and rapid assay time. The magnetically susceptible resultant MIPs (MMIPs) allowed a simple and fast elution of the template molecules from MMIPs, are easily and faster collected without filtration, centrifugation or other complex operations and are also faster assembled and removed from the electrode surface by simply using an external magnetic field. A wide range of different (nano)materials such as gold nanoparticles (AuNPs), graphene oxide, single-walled and multi-walled carbon nanotubes (SWCNTs and MWCNTs) as well as different electrode modifiers (ionic liquids (ILs) and surfactants/dispersants) have been incorporated into the MMIPs to improve the analytical performance of the resulting electrochemical sensors which have demonstrated great promise for determination of relevant analytes in environmental, food and clinical analyses.

  10. [Williams syndrome: its clinical aspects and molecular bases].

    PubMed

    Antonell, A; Del Campo, M; Flores, R; Campuzano, V; Perez-Jurado, L A

    2006-01-07

    Williams syndrome is a developmental disorder with an estimated prevalence of 1 in 7,500 newborns. Its phenotype is characterized by distinctive facial features, mild to moderate mental retardation and general cognitive deficits with a non-uniform profile, having problems in some areas (psychomotricity, visuospatial integration) and relative preservation of others (language, musicality), friendly personality, occasional hypercalcemia of infancy, and a vasculopathy with supravalvular aortic stenosis. Williams syndrome is caused by a submicroscopic deletion of 1.55 Mb in the chromosome band 7q11.23, which includes 26-28 genes. The mutational mechanism consists in a misalignment between regions of almost identical sequence and the subsequent unequal recombination. The reciprocal product of this rearrangement is the duplication of this region, causing a language specific disorder. Clinical-molecular correlations establishment through a good phenotypic characterization and the precise analysis of breakpoints in patients with atypical and typical deletions, altogether with the design of animal models and functional studies in vitro for the genes of the interval will be important to be able to determine the exact contribution of the genes to the phenotype, to know their pathogenesis and physiopathology, and to identify therapeutic methods.

  11. 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

  12. Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

    PubMed Central

    Fukami, Maki; Shozu, Makio; Ogata, Tsutomu

    2012-01-01

    Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s) of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon). These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens. PMID:22319526

  13. Highly-conducting molecular circuits based on antiaromaticity

    NASA Astrophysics Data System (ADS)

    Fujii, Shintaro; Marqués-González, Santiago; Shin, Ji-Young; Shinokubo, Hiroshi; Masuda, Takuya; Nishino, Tomoaki; Arasu, Narendra P.; Vázquez, Héctor; Kiguchi, Manabu

    2017-07-01

    Aromaticity is a fundamental concept in chemistry. It is described by Hückel's rule that states that a cyclic planar π-system is aromatic when it shares 4n+2 π-electrons and antiaromatic when it possesses 4n π-electrons. Antiaromatic compounds are predicted to exhibit remarkable charge transport properties and high redox activities. However, it has so far only been possible to measure compounds with reduced aromaticity but not antiaromatic species due to their energetic instability. Here, we address these issues by investigating the single-molecule charge transport properties of a genuinely antiaromatic compound, showing that antiaromaticity results in an order of magnitude increase in conductance compared with the aromatic counterpart. Single-molecule current-voltage measurements and ab initio transport calculations reveal that this results from a reduced energy gap and a frontier molecular resonance closer to the Fermi level in the antiaromatic species. The conductance of the antiaromatic complex is further modulated electrochemically, demonstrating its potential as a high-conductance transistor.

  14. Molecular and genetic bases of myeloproliferative disorders: questions and perspectives.

    PubMed

    Plo, Isabelle; Vainchenker, William

    2009-01-01

    The discovery of the JAK2V617F mutation followed by the discovery of JAK2 exon 12 and MPLW515 mutations has completely modified the understanding, diagnosis, and management of the classic myeloproliferative disorders (MPDs), which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Nonetheless, genetic defects have not yet been identified in about 40% of ET and PMF. There is now strong evidence that these mutations are the oncogenic events that drive these disorders and are responsible for most biologic and clinical abnormalities. In addition, there are convincing data indicating that the number of JAK2V617F copies (homozygosity vs. heterozygosity) is important in explaining how a single mutation can be associated with several disorders. However, it is still uncertain whether these mutations are sufficient to explain the full development, heterogeneity, and progression of MPD, or if other genetic or epigenetic events are also necessary. In this review, we discuss different hypothetical models of MPD pathogenesis supported by recent findings. Further characterization of the molecular events operating in these disorders will be essential in fully understanding their pathogenesis and in developing new therapeutic approaches.

  15. 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

  16. 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.

  17. 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.

  18. Spin-dependent Seebeck effects in graphene-based molecular junctions

    NASA Astrophysics Data System (ADS)

    Li, Jianwei; Wang, Bin; Xu, Fuming; Wei, Yadong; Wang, Jian

    2016-05-01

    We report a first-principles investigation of spin-dependent transport properties in two different graphene-based molecular junctions. By applying different temperatures between two leads without bias voltage, spin-dependent currents are driven which depend on reference temperature T , temperature gradient Δ T , and gate voltage Vg. Moreover, pure spin currents without charge currents can be obtained by adjusting T ,Δ T , and Vg for both molecular junctions. The directions of pure spin currents in these two molecular junctions are opposite, which can be understood by analyzing the transmission coefficients under equilibrium states. Spin thermopower, thermal conductance, and the figure of merit as functions of T ,Vg, and chemical potential μ were also investigated in the linear response regime. Large spin thermopower and spin figure of merit can be obtained by adjusting Vg and μ for each junction, which indicates proper application of spin caloritronic devices of our graphene-based molecular junctions.

  19. Switchable Negative Differential Resistance Induced by Quantum Interference Effects in Porphyrin-based Molecular Junctions.

    PubMed

    Nozaki, Daijiro; Lokamani; Santana-Bonilla, Alejandro; Dianat, Arezoo; Gutierrez, Rafael; Cuniberti, Gianaurelio

    2015-10-01

    Charge transport signatures of a carbon-based molecular switch consisting of different tautomers of metal-free porphyrin embedded between graphene nanoribbons is studied by combining electronic structure and nonequilibrium transport. Different low-energy and low-bias features are revealed, including negative differential resistance (NDR) and antiresonances, both mediated by subtle quantum interference effects. Moreover, the molecular junctions can display moderate rectifying or nonlinear behavior depending on the position of the hydrogen atoms within the porphyrin core. We rationalize the mechanism leading to NDR and antiresonances by providing a detailed analysis of transmission pathways and frontier molecular orbital distribution.

  20. Spin-polarized transport properties of 1,3-dimethylpropynylidene-based molecular devices

    NASA Astrophysics Data System (ADS)

    Min, Y.; Zhong, C. G.; Yao, K. L.

    2017-10-01

    Based on non-equilibrium Green's function and density functional theory, a first-principles study of the spin-polarized transport properties and magnetism of 1,3-dimethylpropynylidene molecule sandwiched in two Ag electrodes is performed. Strong spin-polarized negative differential resistance and spin filtration effect are present. We also find that the net spin moments of molecular magnet abnormally decrease driven by electric field because the molecular orbitals around Fermi level have opposite spin direction and that non-spin-polarized electrical read out of spin states for single molecular magnets is possible.

  1. 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.

  2. Magnetic wire trap arrays for biomarker-based molecular detection

    NASA Astrophysics Data System (ADS)

    Vieira, Gregory; Mahajan, Kalpesh; Ruan, Gang; Winter, Jessica; Sooryakumar, R.

    2012-02-01

    Submicrometer-scale magnetic devices built on chip-based platforms have recently been shown to present opportunities for new particle trapping and manipulation technologies. Meanwhile, advances in nanoparticle fabrication allow for the building of custom-made particles with precise control of their size, composition, and other properties such as magnetism, fluorescence, and surface biomarker characteristics. In particular, carefully tailored surface biomarkers facilitate precise binding to targeted molecules, self-actuated construction of hybrid structures, and fluorescence-based detection schemes. Based on these progresses, we present an on-chip detection mechanism for molecules with known surface markers. Hybrid nanostructures consisting of micelle nanoparticles, fluorescent quantum dots, and superparamagnetic iron oxide nanoparticles are used to detect proteins or DNA molecules. The target is detected by the magnetic and fluorescent functionalities of the composite nanostructure, whereas in the absence of the target these signals are not present. Underlying this approach is the simultaneous manipulation via ferromagnetic zigzag nanowire arrays and imaging via quantum dot excitation. This chip-based detection technique could provide a powerful, low cost tool for ultrasensitive molecule detection with ramifications in healthcare diagnostics and small-scale chemical synthesis.

  3. Discrete Biogeography Based Optimization for Feature Selection in Molecular Signatures.

    PubMed

    Liu, Bo; Tian, Meihong; Zhang, Chunhua; Li, Xiangtao

    2015-04-01

    Biomarker discovery from high-dimensional data is a complex task in the development of efficient cancer diagnoses and classification. However, these data are usually redundant and noisy, and only a subset of them present distinct profiles for different classes of samples. Thus, selecting high discriminative genes from gene expression data has become increasingly interesting in the field of bioinformatics. In this paper, a discrete biogeography based optimization is proposed to select the good subset of informative gene relevant to the classification. In the proposed algorithm, firstly, the fisher-markov selector is used to choose fixed number of gene data. Secondly, to make biogeography based optimization suitable for the feature selection problem; discrete migration model and discrete mutation model are proposed to balance the exploration and exploitation ability. Then, discrete biogeography based optimization, as we called DBBO, is proposed by integrating discrete migration model and discrete mutation model. Finally, the DBBO method is used for feature selection, and three classifiers are used as the classifier with the 10 fold cross-validation method. In order to show the effective and efficiency of the algorithm, the proposed algorithm is tested on four breast cancer dataset benchmarks. Comparison with genetic algorithm, particle swarm optimization, differential evolution algorithm and hybrid biogeography based optimization, experimental results demonstrate that the proposed method is better or at least comparable with previous method from literature when considering the quality of the solutions obtained.

  4. Tunable separations based on a molecular size effect for biomolecules by poly(ethylene glycol) gel-based capillary electrophoresis.

    PubMed

    Kubo, Takuya; Nishimura, Naoki; Furuta, Hayato; Kubota, Kei; Naito, Toyohiro; Otsuka, Koji

    2017-06-16

    We report novel capillary gel electrophoresis (CGE) with poly(ethylene glycol) (PEG)-based hydrogels for the effective separations of biomolecules containing sugars and DNAs based on a molecular size effect. The gel capillaries were prepared in a fused silica capillary modified with 3-(trimethoxysilyl)propylmethacrylate using a variety of the PEG-based hydrogels. After the fundamental evaluations in CGE regarding the separation based on the molecular size effect depending on the crosslinking density, the optimized capillary provided the efficient separation of glucose ladder (G1 to G20). In addition, another capillary showed the successful separation of DNA ladder in the range of 10-1100 base pair, which is superior to an authentic acrylamide-based gel capillary. For both glucose and DNA ladders, the separation ranges against the molecular size were simply controllable by alteration of the concentration and/or units of ethylene oxide in the PEG-based crosslinker. Finally, we demonstrated the separations of real samples, which included sugars carved out from monoclonal antibodies, mAbs, and then the efficient separations based on the molecular size effect were achieved. Copyright © 2017. Published by Elsevier B.V.

  5. 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.

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

    PubMed Central

    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

  7. 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.

  8. 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.

  9. 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.

  10. Molecular engineering of manipulated alginate-based polyurethanes.

    PubMed

    Daemi, Hamed; Barikani, Mehdi

    2014-11-04

    The novel soluble alginate-based polyurethanes in organic solvents were synthesized by the reaction of NCO-terminated prepolymers and tributylammonium alginate (TBA-Alg) for the first time. The chemical structures of synthesized polyurethanes were characterized using FTIR, (1)H NMR and TGA. The reaction completion was confirmed by disappearing of NCO band in FTIR spectra. Furthermore, a peak at 4.71 ppm and some small peaks at a range of 4.12-4.37 ppm in the (1)H NMR of alginate-based polyurethanes were assigned to the backbone of alginate. The results of both FTIR and (1)H NMR were remarkably confirmed by TGA data. The ionic nature of polyurethane backbone not only affects on thermal properties of samples, but it also changes the chemically-bonded alginate morphology. Both polyether and polyester based non-ionic polyurethanes extended by TBA-Alg illustrated the distinct alginate, whereas those ionomers extended by alginate were appeared as the continuous systems at nanoscale.

  11. iBarcode.org: web-based molecular biodiversity analysis.

    PubMed

    Singer, Gregory A C; Hajibabaei, Mehrdad

    2009-06-16

    DNA sequences have become a primary source of information in biodiversity analysis. For example, short standardized species-specific genomic regions, DNA barcodes, are being used as a global standard for species identification and biodiversity studies. Most DNA barcodes are being generated by laboratories that have an expertise in DNA sequencing but not in bioinformatics data analysis. Therefore, we have developed a web-based suite of tools to help the DNA barcode researchers analyze their vast datasets. Our web-based tools, available at http://www.ibarcode.org, allow the user to manage their barcode datasets, cull out non-unique sequences, identify haplotypes within a species, and examine the within- to between-species divergences. In addition, we provide a number of phylogenetics tools that will allow the user to manipulate phylogenetic trees generated by other popular programs. The use of a web-based portal for barcode analysis is convenient, especially since the WWW is inherently platform-neutral. Indeed, we have even taken care to ensure that our website is usable from handheld devices such as PDAs and smartphones. Although the current set of tools available at iBarcode.org were developed to meet our own analytic needs, we hope that feedback from users will spark the development of future tools. We also welcome user-built modules that can be incorporated into the iBarcode framework.

  12. 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.

  13. 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.

  14. A model for integrating molecular-based testing in transfusion services

    PubMed Central

    Sandler, S. Gerald; Horn, Trina; Keller, Jessica; Langeberg, Al; Keller, Margaret A.

    2016-01-01

    Background Molecular-based laboratory tests can predict blood group antigens and supplement serological methods, adding a unique technology to assist in resolving discrepant or incomplete blood group typing or antibody identification. Hospital transfusion services have options for integrating molecular-based methods in their routine operations. We describe here the model of a hospital-reference laboratory partnership. Materials and methods Blood samples for compatibility testing were obtained from patients in a 609-bed hospital serving an urban multiethnic and multiracial population. When results of blood group phenotyping by serological methods were inconclusive, samples were referred for molecular-based testing. The reference laboratory used several methods for genotyping, including polymerase chain reaction followed by restriction enzyme-linked polymorphism analysis, sequence-specific primer polymerase chain reaction and array-based approaches. Human erythrocyte antigen, RHCE and RHD single nucleotide polymorphism arrays were integrated into the laboratory as they became commercially available. Results The hospital-reference laboratory model made it possible to integrate blood group genotyping promptly by current technology without the expense of new laboratory equipment or adding personnel with technical expertise. We describe ten cases that illustrate the categories of serological problems that were resolved by molecular methods. Discussion In-hospital molecular testing for transfusion services has logistical advantages, but is financially impractical for most hospitals. Our model demonstrates the advantages of a hospital-reference laboratory partnership. In conclusion, hospital transfusion services can integrate molecular-based testing in their routine services without delay by establishing a partnership with a molecular blood group reference laboratory. The hospital reference-laboratory model promotes genomic medicine without the expense of new equipment and

  15. New Polynomial-Based Molecular Descriptors with Low Degeneracy

    PubMed Central

    Dehmer, Matthias; Mueller, Laurin A. J.; Graber, Armin

    2010-01-01

    In this paper, we introduce a novel graph polynomial called the ‘information polynomial’ of a graph. This graph polynomial can be derived by using a probability distribution of the vertex set. By using the zeros of the obtained polynomial, we additionally define some novel spectral descriptors. Compared with those based on computing the ordinary characteristic polynomial of a graph, we perform a numerical study using real chemical databases. We obtain that the novel descriptors do have a high discrimination power. PMID:20689599

  16. Molecular Engineering of Technetium and Rhenium Based Radiopharmaceuticals

    SciTech Connect

    Zubieta, J.

    2003-06-30

    The research was based on the observation that despite the extraordinarily rich coordination chemistry of technetium and rhenium and several notable successes in reagent design, the extensive investigations by numerous research groups on a variety of N{sub 2}S{sub 2} and N{sub 3}S donor type ligands and on HYNIC have revealed that the chemistries of these ligands with Tc and Re are rather complex, giving rise to considerable difficulties in the development of reliable procedures for the development of radiopharmaceutical reagents.

  17. Structure Controlled Long-Range Sequential Tunneling in Carbon-Based Molecular Junctions.

    PubMed

    Morteza Najarian, Amin; McCreery, Richard L

    2017-04-25

    Carbon-based molecular junctions consisting of aromatic oligomers between conducting sp(2) hybridized carbon electrodes exhibit structure-dependent current densities (J) when the molecular layer thickness (d) exceeds ∼5 nm. All four of the molecular structures examined exhibit an unusual, nonlinear ln J vs bias voltage (V) dependence which is not expected for conventional coherent tunneling or activated hopping mechanisms. All molecules exhibit a weak temperature dependence, with J increasing typically by a factor of 2 over the range of 200-440 K. Fluorene and anthraquinone show linear plots of ln J vs d with nearly identical J values for the range d = 3-10 nm, despite significant differences in their free-molecule orbital energy levels. The observed current densities for anthraquinone, fluorene, nitroazobenzene, and bis-thienyl benzene for d = 7-10 nm show no correlation with occupied (HOMO) or unoccupied (LUMO) molecular orbital energies, contrary to expectations for transport mechanisms based on the offset between orbital energies and the electrode Fermi level. UV-vis absorption spectroscopy of molecular layers bonded to carbon electrodes revealed internal energy levels of the chemisorbed films and also indicated limited delocalization in the film interior. The observed current densities correlate well with the observed UV-vis absorption maxima for the molecular layers, implying a transport mechanism determined by the HOMO-LUMO energy gap. We conclude that transport in carbon-based aromatic molecular junctions is consistent with multistep tunneling through a barrier defined by the HOMO-LUMO gap, and not by charge transport at the electrode interfaces. In effect, interfacial "injection" at the molecule/electrode interfaces is not rate limiting due to relatively strong electronic coupling, and transport is controlled by the "bulk" properties of the molecular layer interior.

  18. A molecular marker based linkage map of Vitis.

    PubMed

    Lodhi, M A; Daly, M J; Ye, G N; Weeden, N F; Reisch, B I

    1995-08-01

    Genetic linkage maps of Vitis (2n = 38) have been constructed from a single interspecific hybrid grape population (60 seedlings) of 'Cayuga White' X 'Aurore'. The maps were primarily based on 422 RAPD markers but also included 16 RFLP and isozyme markers. These maps had an average distance of 6.1 cM between markers and were developed using a double-pseudotestcross strategy. The 'Cayuga White' map had 214 markers covering 1196 cM and that of 'Aurore' spanned over 1477 cM with 225 markers. The 'Cayuga White' map consisted of 20 linkage groups, whereas 22 linkage groups comprised the 'Aurore' map. The number of groups reduced to 19, as in some instances two or more groups from one parent showed homology with a single group from the other parent on the basis of markers heterozygous in both parents. Each linkage group ranged in size from 14 to 135 cM in 'Aurore' and from 14 to 124 cM in 'Cayuga White'. These maps provide enough coverage of the genome to allow quantitative trait locus analysis and map-based gene cloning.

  19. 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

  20. Microbial detection method based on sensing molecular hydrogen.

    PubMed

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

    1974-05-01

    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 (i) two electrodes, platinum and a reference electrode, (ii) a buffer amplifier, and (iii) a strip-chart recorder. Hydrogen evolution was measured by an increase in voltage in the negative (cathodic) direction and recorded on a strip-chart recorder. Hydrogen response curves consisted of (i) a lag period, (ii) a period of rapid buildup in potential due to hydrogen, and (iii) a period of decline in potential. A linear relationship was established between inoculum size and the time hydrogen was detected (lag period). Lag times ranged from 1 h for 10(6) cells/ml to 7 h for 10(0) cells/ml. For each 10-fold decrease in inoculum, length of the lag period increased 60 to 70 min. Mean cell concentrations at the time of hydrogen evolution were 10(6)/ml. Based on the linear relationship between inoculum size 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.

  1. 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

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

    PubMed

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

    2012-09-15

    The Gauss-Seidel (GS) 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 GS 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 processes or computing units. 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.

  3. 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

  4. Singlet oxygen-based electrosensing by molecular photosensitizers

    NASA Astrophysics Data System (ADS)

    Trashin, Stanislav; Rahemi, Vanoushe; Ramji, Karpagavalli; Neven, Liselotte; Gorun, Sergiu M.; de Wael, Karolien

    2017-07-01

    Enzyme-based electrochemical biosensors are an inspiration for the development of (bio)analytical techniques. However, the instability and reproducibility of the reactivity of enzymes, combined with the need for chemical reagents for sensing remain challenges for the construction of useful devices. Here we present a sensing strategy inspired by the advantages of enzymes and photoelectrochemical sensing, namely the integration of aerobic photocatalysis and electrochemical analysis. The photosensitizer, a bioinspired perfluorinated Zn phthalocyanine, generates singlet-oxygen from air under visible light illumination and oxidizes analytes, yielding electrochemically-detectable products while resisting the oxidizing species it produces. Compared with enzymatic detection methods, the proposed strategy uses air instead of internally added reactive reagents, features intrinsic baseline correction via on/off light switching and shows C-F bonds-type enhanced stability. It also affords selectivity imparted by the catalytic process and nano-level detection, such as 20 nM amoxicillin in μl sample volumes.

  5. Singlet oxygen-based electrosensing by molecular photosensitizers

    PubMed Central

    Trashin, Stanislav; Rahemi, Vanoushe; Ramji, Karpagavalli; Neven, Liselotte; Gorun, Sergiu M.; De Wael, Karolien

    2017-01-01

    Enzyme-based electrochemical biosensors are an inspiration for the development of (bio)analytical techniques. However, the instability and reproducibility of the reactivity of enzymes, combined with the need for chemical reagents for sensing remain challenges for the construction of useful devices. Here we present a sensing strategy inspired by the advantages of enzymes and photoelectrochemical sensing, namely the integration of aerobic photocatalysis and electrochemical analysis. The photosensitizer, a bioinspired perfluorinated Zn phthalocyanine, generates singlet-oxygen from air under visible light illumination and oxidizes analytes, yielding electrochemically-detectable products while resisting the oxidizing species it produces. Compared with enzymatic detection methods, the proposed strategy uses air instead of internally added reactive reagents, features intrinsic baseline correction via on/off light switching and shows C-F bonds-type enhanced stability. It also affords selectivity imparted by the catalytic process and nano-level detection, such as 20 nM amoxicillin in μl sample volumes.

  6. 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.

  7. 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.

  8. Manganese-Based Molecular Electrocatalysts for Oxidation of Hydrogen

    SciTech Connect

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

    2015-11-06

    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; 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 700 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 880 mV. Density functional theory calculations suggest that the slow step in the catalytic cycle is proton transfer from the oxidized 17-electron manganese hydride [(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 for [(P2N2)MnIIH(CO)(bppm)]+ and 21.3 kcal/mol for [(PNP)MnIIH(CO)(bppm)]+. The high barrier appears to result from both the unfavorability of the metal to nitrogen proton transfer (thermodynamically uphill by 9 kcal/mol for [(P2N2)MnIIH(CO)(bppm)]+ due to a mismatch of 6.6 pKa units) and the relatively long manganese–nitrogen separation in the MnIIH complexes.

  9. Raoult's law-based method for determination of coal tar average molecular weight

    SciTech Connect

    Brown, D.G.; Gupta, L.; Horace, H.K.; Coleman, A.J.

    2005-08-01

    A Raoult's law-based method for determining the number average molecular weight of coal tars is presented. The method requires data from two-phase coal tar/water equilibrium experiments, which readily are performed in environmental laboratories. An advantage of this method for environmental samples is that it is not impacted by the small amount of inert debris often present in coal tar samples obtained from contaminated sites. Results are presented for 10 coal tars from nine former manufactured gas plants located in the eastern United States. Vapor pressure osmometry (VPO) analysis provided similar average molecular weights to those determined with the Raoult's law-based method, except for one highly viscous coal tar sample. Use of the VPO-based average molecular weight for this coal tar resulted in underprediction of the coal tar constituents' aqueous concentrations. Additionally, one other coal tar was not completely soluble in solvents used for VPO analysis. The results indicate that the Raoult's law-based method is able to provide an average molecular weight that is consistent with the intended application of the data (e.g., modeling the dissolution of coal tar constituents into surrounding waters), and this method can be applied to coal tars that may be incompatible with other commonly used methods for determining average molecular weight, such as vapor pressure osmometry.

  10. Thiacalix[4]arene based reconfigurable molecular switches: set-reset memorized sequential device.

    PubMed

    Kumar, Manoj; Kumar, Rajesh; Bhalla, Vandana

    2011-12-21

    The fluorescent chemosensors 3, 5 and 7 based on thiacalix[4]arene bearing naphthyl groups have been designed and synthesized. The optical chemosensor 3 based on a thiacalix[4]arene of cone conformation behaves as "turn-on" optical chemosensor for Fe(3+) and F(-) ions. However, chemosensors 5 and 7 based on a thiacalix[4]arene of 1,3-alternate conformation demonstrate "turn-on" optical behaviour for Hg(2+), F(-) ions (with receptor 5 as turn-on for K(+) ions also) and "turn-off" behaviour for Fe(3+) ions. The simultaneous presence of Fe(3+) and Hg(2+) or K(+) or F(-) ions results in formulation of reversible "on-off" switches. Various molecular logic gates developed in response to molecular switching between these chemical inputs have been integrated into sequential logic circuits with memory function in a feedback loop which mimics "set-reset" molecular level information processing device.

  11. 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.

  12. Algorithms and novel applications based on the isokinetic ensemble. I. Biophysical and path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Minary, Peter; Martyna, Glenn J.; Tuckerman, Mark E.

    2003-02-01

    In this paper (Paper I) and a companion paper (Paper II), novel new algorithms and applications of the isokinetic ensemble as generated by Gauss' principle of least constraint, pioneered for use with molecular dynamics 20 years ago, are presented for biophysical, path integral, and Car-Parrinello based ab initio molecular dynamics. In Paper I, a new "extended system" version of the isokinetic equations of motion that overcomes the ergodicity problems inherent in the standard approach, is developed using a new theory of non-Hamiltonian phase space analysis [M. E. Tuckerman et al., Europhys. Lett. 45, 149 (1999); J. Chem. Phys. 115, 1678 (2001)]. Reversible multiple time step integrations schemes for the isokinetic methods, first presented by Zhang [J. Chem. Phys. 106, 6102 (1997)] are reviewed. Next, holonomic constraints are incorporated into the isokinetic methodology for use in fast efficient biomolecular simulation studies. Model and realistic examples are presented in order to evaluate, critically, the performance of the new isokinetic molecular dynamic schemes. Comparisons are made to the, now standard, canonical dynamics method, Nosé-Hoover chain dynamics [G. J. Martyna et al., J. Chem. Phys. 97, 2635 (1992)]. The new isokinetic techniques are found to yield more efficient sampling than the Nosé-Hoover chain method in both path integral molecular dynamics and biophysical molecular dynamics calculations. In Paper II, the use of isokinetic methods in Car-Parrinello based ab initio molecular dynamics calculations is presented.

  13. Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

    PubMed

    Islam, Md Ataul; Pillay, Tahir S

    2017-01-21

    In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB.

  14. Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data

    PubMed Central

    Raes, Jeroen; Letunic, Ivica; Yamada, Takuji; Jensen, Lars Juhl; Bork, Peer

    2011-01-01

    Using metagenomic ‘parts lists' to infer global patterns on microbial ecology remains a significant challenge. To deduce important ecological indicators such as environmental adaptation, molecular trait dispersal, diversity variation and primary production from the gene pool of an ecosystem, we integrated 25 ocean metagenomes with geographical, meteorological and geophysicochemical data. We find that climatic factors (temperature, sunlight) are the major determinants of the biomolecular repertoire of each sample and the main limiting factor on functional trait dispersal (absence of biogeographic provincialism). Molecular functional richness and diversity show a distinct latitudinal gradient peaking at 20°N and correlate with primary production. The latter can also be predicted from the molecular functional composition of an environmental sample. Together, our results show that the functional community composition derived from metagenomes is an important quantitative readout for molecular trait-based biogeography and ecology. PMID:21407210

  15. 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.

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

    DOE PAGES

    Ding, Wendu; Koepf, Matthieu; Koenigsmann, Christopher; ...

    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

  17. 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.

  18. 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

  19. Open-Shell-Character-Based Molecular Design Principles: Applications to Nonlinear Optics and Singlet Fission.

    PubMed

    Nakano, Masayoshi

    2017-01-01

    Open-shell character, e. g., diradical character, is a quantum chemically well-defined quantity in ground-state molecular systems, which is not an observable but can quantify the degree of effective bond weakness in the chemical sense or electron correlation strength in the physical sense. Because this quantity also correlates to specific excited states, physicochemical properties concerned with those states are expected to strongly correlate to the open-shell character. This feature enables us to open a new path to revealing the mechanism of these properties as well as to realizing new design principles for efficient functional molecular systems. This account explains the open-shell-character-based molecular design principles and introduces their applications to the rational design of highly efficient nonlinear optical and singlet fission molecular systems. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 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.

  1. Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data.

    PubMed

    Raes, Jeroen; Letunic, Ivica; Yamada, Takuji; Jensen, Lars Juhl; Bork, Peer

    2011-03-15

    Using metagenomic 'parts lists' to infer global patterns on microbial ecology remains a significant challenge. To deduce important ecological indicators such as environmental adaptation, molecular trait dispersal, diversity variation and primary production from the gene pool of an ecosystem, we integrated 25 ocean metagenomes with geographical, meteorological and geophysicochemical data. We find that climatic factors (temperature, sunlight) are the major determinants of the biomolecular repertoire of each sample and the main limiting factor on functional trait dispersal (absence of biogeographic provincialism). Molecular functional richness and diversity show a distinct latitudinal gradient peaking at 20° N and correlate with primary production. The latter can also be predicted from the molecular functional composition of an environmental sample. Together, our results show that the functional community composition derived from metagenomes is an important quantitative readout for molecular trait-based biogeography and ecology.

  2. 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.

  3. 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.

  4. 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.

  5. Radical gas-based DNA decontamination for ultra-sensitive molecular experiments.

    PubMed

    Morono, Yuki; Yamamoto, Katsuhiro; Inagaki, Fumio

    2012-01-01

    In this study, we tested a radical gas-based decontamination technique to prevent possible DNA contamination by the air and/or equipment used in molecular experiments. We prepared 10(4) molecules of model DNA contaminant and placed the dried DNA into test tubes, which were then exposed to radical gas. Quantitative PCR analysis showed that, even after a short exposure time of 30 minutes, 99.54% of the model DNA contaminant was effectively decomposed to undetectable levels. Our results demonstrate that the radical gas-based treatment is a useful method for eliminating potential DNA contaminant in ultra-sensitive molecular experiments.

  6. 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.

  7. Model of self assembled monolayer based molecular diodes made of ferrocenyl-alkanethiols

    NASA Astrophysics Data System (ADS)

    Duche, David; Planchoke, Ujwol; Dang, Florian-Xuan; Le Rouzo, Judikael; Bescond, Marc; Simon, Jean-Jacques; Balaban, Teodor Silviu; Escoubas, Ludovic

    2017-03-01

    There has been significant work investigating the use of self assembled monolayers (SAMs) made of ferrocenyl terminated alkanethiols for realizing molecular diodes, leading to remarkably large forward-to-reverse current rectification ratios. In this study, we use a multiband barrier tunneling model to examine the electrical properties of SAM-based molecular diodes made of HSC9Fc, HSC11Fc, and HSCiFcC13-i (0 ≤ i ≤ 13). Using our simple physical model, we reproduce the experimental data of charge transport across various ferrocenyl substituted alkanethiols performed by Nijhuis, Reus, and Whitesides [J. Am. Chem. Soc. 132, 18386-184016 (2010)] and Yuan et al. [Nat. Commun. 6, 6324 (2015)]. Especially, the model allows predicting the rectification direction in HSCiFcC13-i (0 ≤ i ≤ 13) based molecular diodes depending on the position of the ferrocenyl (Fc) moiety within the molecules. We show that the asymmetry of the barrier length at both sides of the Highest Occupied Molecular Orbital of the ferrocenyl moiety strongly contributes to the rectifying properties of ferrocenyl-alkanethiol based molecular junctions. Furthermore, our results reveal that bound and quasi-bound states play an important role in the charge transport.

  8. Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling.

    PubMed

    Wang, M; Lindberg, J; Klevebring, D; Nilsson, C; Mer, A S; Rantalainen, M; Lehmann, S; Grönberg, H

    2017-10-01

    Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value<0.05; concordance index >0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.

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

    PubMed

    Kachman, Stephen D; Spangler, Matthew L; Bennett, Gary L; Hanford, Kathryn J; Kuehn, Larry A; Snelling, Warren M; Thallman, R Mark; Saatchi, Mahdi; Garrick, Dorian J; Schnabel, Robert D; Taylor, Jeremy F; Pollak, E John

    2013-08-16

    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. 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. 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. 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 set, across- and within-breed trained

  10. 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.

  11. Modelling and enhanced molecular dynamics to steer structure-based drug discovery.

    PubMed

    Kalyaanamoorthy, Subha; Chen, Yi-Ping Phoebe

    2014-05-01

    The ever-increasing gap between the availabilities of the genome sequences and the crystal structures of proteins remains one of the significant challenges to the modern drug discovery efforts. The knowledge of structure-dynamics-functionalities of proteins is important in order to understand several key aspects of structure-based drug discovery, such as drug-protein interactions, drug binding and unbinding mechanisms and protein-protein interactions. This review presents a brief overview on the different state of the art computational approaches that are applied for protein structure modelling and molecular dynamics simulations of biological systems. We give an essence of how different enhanced sampling molecular dynamics approaches, together with regular molecular dynamics methods, assist in steering the structure based drug discovery processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Hydration of Watson-Crick base pairs and dehydration of Hoogsteen base pairs inducing structural polymorphism under molecular crowding conditions.

    PubMed

    Miyoshi, Daisuke; Nakamura, Kaori; Tateishi-Karimata, Hisae; Ohmichi, Tatsuo; Sugimoto, Naoki

    2009-03-18

    It has been revealed recently that molecular crowding, which is one of the largest differences between in vivo and in vitro conditions, is a critical factor determining the structure, stability, and function of nucleic acids. However, the effects of molecular crowding on Watson-Crick and Hoogsteen base pairs remain unclear. In order to investigate directly and quantitatively the molecular crowding effects on base pair types in nucleic acids, we designed intramolecular parallel- and antiparallel-stranded DNA duplexes consisting of Hoogsteen and Watson-Crick base pairs, respectively, as well as an intramolecular parallel-stranded triplex containing both types of base pairs. Thermodynamic analyses demonstrated that the values of free energy change at 25 degrees C for Hoogsteen base-pair formations decreased from +1.45 +/- 0.15 to +1.09 +/- 0.13 kcal mol(-1), and from -1.89 +/- 0.13 to -2.71 +/- 0.11 kcal mol(-1) in the intramolecular duplex and triplex, respectively, when the concentration of PEG 200 (polyethylene glycol with average molecular weight 200) increased from 0 to 20 wt %. However, corresponding values for Watson-Crick formation in the duplex and triplex increased from -10.2 +/- 0.2 to -8.7 +/- 0.1 kcal mol(-1), and from -10.8 +/- 0.2 to -9.2 +/- 0.2 kcal mol(-1), respectively. Furthermore, it was revealed that the opposing effects of molecular crowding on the Hoogsteen and Watson-Crick base pairs were due to different behaviors of water molecules binding to the DNA strands.

  13. 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.

  14. Is liquid-based cytology the magic bullet for performing molecular techniques?

    PubMed

    Abedi-Ardekani, Behnoush; Vielh, Philippe

    2014-01-01

    The role of pathology has evolved from the first microscopic definitions of diseases by Virchow to the new concept of molecular cytopathology. The management of diseases is now a multidisciplinary approach with the translation of morphological, imagery and molecular findings to therapeutic protocols. Obtaining the most reliable diagnostic material is the essential part of the medical management of patients. Here, we try to gain a concise insight into the available data regarding the role of cytology in the application of molecular techniques, focusing on cancer cytopathology. Obtaining cytological material is now feasible by different methods, and in some cases it is the only possible approach to a lesion which is not easily accessible for tissue sampling. The methods of obtaining cytological material have evolved in recent years in parallel with rapid advances in high-throughput molecular techniques, opening new windows for the diagnosis and management of diseases. Different kinds of cytological material are reliable for the application of molecular techniques. Cytological material obtained in a liquid base has advantages such as the better preservation of cytomorphological features and the use of the remaining liquid for nucleic acid extraction even after long storage and the application of molecular methods.

  15. Nanomicrointerface to read molecular potentials into current-voltage based electronics.

    PubMed

    Rangel, Norma L; Seminario, Jorge M

    2008-03-21

    Molecular potentials are unreadable and unaddressable by any present technology. It is known that the proper assembly of molecules can implement an entire numerical processing system based on digital or even analogical computation. In turn, the outputs of this molecular processing unit need to be amplified in order to be useful. We have developed a nanomicrointerface to read information encoded in molecular level potentials and to amplify this signal to microelectronic levels. The amplification is performed by making the output molecular potential slightly twist the torsional angle between two rings of a pyridazine, 3,6-bis(phenylethynyl) (aza-OPE) molecule, requiring only fractions of kcal/mol energies. In addition, even if the signal from the molecular potentials is not enough to turn the ring or even if the angles are the same for different combinations of outputs, still the current output yields results that resemble the device as a field effect transistor, providing the possibility to reduce channel lengths to the range of just 1 or 2 nm. The slight change in the torsional angle yields readable changes in the current through the aza-OPE biased by an external applied voltage. Using ab initio methods, we computationally demonstrate the amplification of molecular potential signals into currents that can be read by standard circuits.

  16. [New strategies in the clinical evaluation of patients with colon cancer based on molecular studies].

    PubMed

    Panduro, A; Morales, L; Santos, A; Valdés, L; Lima, G; Meléndez, J; Cabrera, G; Maldonado, V; Villalobos, J J

    1993-01-01

    During the last five years molecular studies allowed important advances in the knowledge of cancer colon with important clinical implications. The main finding was the identification and sequence analysis of the APC gen. Structural alterations of this gene have been detected in patients with Familial Adenomatous Polyposis and Gardner syndrome, which suggest a common disease. Furthermore, alterations of the APC gen appears to be also altered in cases of cancer of colon sporadic. Indicating that structural alteration of the APC gen can be inherited and/or acquired. Restriction fragment-length polymorphisms in the chromosome 5q21-22 can now be used clinically for premorbid diagnosis and counseling in familial adenomatous polyposis. The molecular studies allow the clinician to have a new approach in the management and screening of families with familial adenomatous polyposis. The sequence analysis and specific identification of the structural alteration of the APC gene is a more expensive and sophisticated study, although represent a more direct approach. In the Department of Gastroenterology of the INNSZ we are performing such molecular studies. The main purpose of our group is to proportionate integral clinical-molecular studies for families with hereditary colon cancer, create a national register of these diseases and investigate the molecular bases in order to generate new molecular diagnosis tools.

  17. 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.

  18. The Value of Molecular Haplotypes in a Family-Based Linkage Study

    PubMed Central

    Gillanders, E. M.; Pearson, J. V.; Sorant, A. J. M.; Trent, J. M.; O’Connell, J. R.; Bailey-Wilson, J. E.

    2006-01-01

    Novel methods that could improve the power of conventional methods of gene discovery for complex diseases should be investigated. In a simulation study, we aimed to investigate the value of molecular haplotypes in the context of a family-based linkage study. The term “haplotype” (or “haploid genotype”) refers to syntenic alleles inherited on a single chromosome, and we use the term “molecular haplotype” to refer to haplotypes that have been determined directly by use of a molecular technique such as long-range allele-specific polymerase chain reaction. In our study, we simulated genotype and phenotype data and then compared the powers of analyzing these data under the assumptions that various levels of information from molecular haplotypes were available. (This information was available because of the simulation procedure.) Several conclusions can be drawn. First, as expected, when genetic homogeneity is expected or when marker data are complete, it is not efficient to generate molecular haplotyping information. However, with levels of heterogeneity and missing data patterns typical of complex diseases, we observed a 23%–77% relative increase in the power to detect linkage in the presence of heterogeneity with heterogeneity LOD scores >3.0 when all individuals are molecularly haplotyped (compared with the power when only standard genotypes are used). Furthermore, our simulations indicate that most of the increase in power can be achieved by molecularly haplotyping a single individual in each family, thereby making molecular haplotyping a valuable strategy for increasing the power of gene mapping studies of complex diseases. Maximization of power, given an existing family set, can be particularly important for late-onset, often-fatal diseases such as cancer, for which informative families are difficult to collect. PMID:16909384

  19. Photonics-based strategies for minimally invasive cancer diagnosis using endogenous and molecular contrast

    NASA Astrophysics Data System (ADS)

    Sun, Jiantang

    Optical- and spectroscopic-based screening and imaging strategies possess unique advantages for minimally invasive cancer diagnosis. In this dissertation, we investigated how diagnostic results based on such techniques can be improved by the utilization of both endogenous and nanotechnology-facilitated molecular contrast. First, a diffusion-theory-based inversion reflectance model was constructed for the extraction of intrinsic tissue optical properties from the shape of normalized tissue diffusion reflectance spectra. The accuracy of our diffusion-based inversion algorithm was systematically assessed against Monte Carlo simulation as a function of probe geometry and tissue optical property combinations. By using this method, the spectral absorption and scattering coefficients of normal and cancerous tissue were efficiently retrieved within the center-to-center source-detector fiber separation of 0.5 mm ˜3 mm, which is compatible with endoscopic specifications. The presented inversion approach is computationally viable for eventual real-time in vivo tissue diagnostic applications. Second, novel quantum dot nanoparticle-based contrast agents were developed for molecular and tissue imaging applications in the visible and near-infrared (NIR) spectral ranges. Specifically, lead sulfide quantum dot bioconjugates were explored as NIR contrast agents for targeted molecular imaging; a protease-activated quantum dot probe was developed to monitor specific molecular targets and pathways through optical strategies; and a phantom study was conducted to assess the utilization of lead sulfide NIR quantum dots as fluorescent contrast agents for deep tissue imaging applications. These nanoengineered exogenous probes were shown to have the potential to significantly improve the implementation of optical/spectroscopic cancer imaging techniques. Taken together, the goal of the combined projects in this dissertation was to demonstrate that photonics-based minimally invasive cancer

  20. Quantum Computing Using Pulse-Based Electron-Nuclear Double Resonance (endor):. Molecular Spin-Qubits

    NASA Astrophysics Data System (ADS)

    Sato, Kazuo; Nakazawa, Shigeki; Rahimi, Robabeh D.; Nishida, Shinsuke; Ise, Tomoaki; Shimoi, Daisuke; Toyota, Kazuo; Morita, Yasushi; Kitagawa, Masahiro; Carl, Parick; Höfner, Peter; Takui, Takeji

    2009-06-01

    Electrons with the spin quantum number 1/2, as physical qubits, have naturally been anticipated for implementing quantum computing and information processing (QC/QIP). Recently, electron spin-qubit systems in organic molecular frames have emerged as a hybrid spin-qubit system along with a nuclear spin-1/2 qubit. Among promising candidates for QC/QIP from the materials science side, the reasons for why electron spin-qubits such as molecular spin systems, i.e., unpaired electron spins in molecular frames, have potentialities for serving for QC/QIP will be given in the lecture (Chapter), emphasizing what their advantages or disadvantages are entertained and what technical and intrinsic issues should be dealt with for the implementation of molecular-spin quantum computers in terms of currently available spin manipulation technology such as pulse-based electron-nuclear double resonance (pulsed or pulse ENDOR) devoted to QC/QIP. Firstly, a general introduction and introductory remarks to pulsed ENDOR spectroscopy as electron-nuclear spin manipulation technology is given. Super dense coding (SDC) experiments by the use of pulsed ENDOR are also introduced to understand differentiating QC ENDOR from QC NMR based on modern nuclear spin technology. Direct observation of the spinor inherent in an electron spin, detected for the first time, will be shown in connection with the entanglement of an electron-nuclear hybrid system. Novel microwave spin manipulation technology enabling us to deal with genuine electron-electron spin-qubit systems in the molecular frame will be introduced, illustrating, from the synthetic strategy of matter spin-qubits, a key-role of the molecular design of g-tensor/hyperfine-(A-)tensor molecular engineering for QC/QIP. Finally, important technological achievements of recently-emerging CD ELDOR (Coherent-Dual ELectron-electron DOuble Resonance) spin technology enabling us to manipulate electron spin-qubits are described.

  1. 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.

  2. 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. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  4. Phylogenetic relationships of Iberian Aphodiini (Coleoptera: Scarabaeidae) based on morphological and molecular data.

    PubMed

    Cabrero-Sañudo, Francisco-José; Zardoya, Rafael

    2004-06-01

    A phylogeny of Iberian Aphodiini dung beetles was reconstructed based on morphological and molecular data. The data set included a total of 84 variable characters from wing venation, mouthparts, genitalia, and external morphology, as well as mitochondrial partial cytochrome c oxidase I (COI), complete tRNA-Leu (UUR), and partial cytochrome c oxidase II (COII) gene nucleotide sequences (1210 positions). Phylogenetic trees based on molecular data were relatively more resolved than those based on morphological characters. The Bayesian analysis of combined molecular and morphological data provided resolution not achieved by each data set separately. Ammoecius and Aphodius are the first lineages that branch off from the tree, followed by Acrossus, Nimbus, and Heptaulacus. The remaining studied taxa are recovered in a more derived clade that lacks internal resolution. Reconstructed trees based on molecular data showed relatively short internal nodes that were weakly supported. Such pattern may reflect a rapid radiation at the origin of the tribe Aphodiini, but also saturation of mutational changes. Several tests were conducted to discern between both competing hypotheses, as well as to assess the effect of incomplete taxon sampling.

  5. 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…

  6. 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…

  7. Development of new candidate gene and EST-based molecular markers for Gossypium species

    USDA-ARS?s Scientific Manuscript database

    New source of molecular markers accelerates the efforts in improving cotton fiber traits and aid in developing high-density integrated genetic maps. We developed new markers based on candidate genes and G. arboreum expressed sequence tag (EST) sequences, and validated them through amplification, ge...

  8. 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…

  9. 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…

  10. 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.

  11. A differential ICT based molecular probe for multi-ions and multifunction logic circuits.

    PubMed

    Luxami, Vijay; Kumar, Subodh

    2012-04-21

    This paper presents anthraquinone and benzimidazole based hybrid molecular architect as the state of the art for multifunctional molecular logic circuits. The moleculator exhibits differential output behavior towards F(-), Zn(2+) and Cu(2+) ions to provide opportunities for elaboration of XOR, INHIBIT, XNOR, AND, OR, NOR, logic functions and their integrated logic functions half-adder, half-subtractor and comparator within a single molecule. These integral logic functions can be reprogrammed by self-annihilation or by another additional input in the same cell. This single molecule behaves uniquely where different logic functions can be operated and reset by using different inputs and outputs.

  12. pyPcazip: A PCA-based toolkit for compression and analysis of molecular simulation data

    NASA Astrophysics Data System (ADS)

    Shkurti, Ardita; Goni, Ramon; Andrio, Pau; Breitmoser, Elena; Bethune, Iain; Orozco, Modesto; Laughton, Charles A.

    The biomolecular simulation community is currently in need of novel and optimised software tools that can analyse and process, in reasonable timescales, the large generated amounts of molecular simulation data. In light of this, we have developed and present here pyPcazip: a suite of software tools for compression and analysis of molecular dynamics (MD) simulation data. The software is compatible with trajectory file formats generated by most contemporary MD engines such as AMBER, CHARMM, GROMACS and NAMD, and is MPI parallelised to permit the efficient processing of very large datasets. pyPcazip is a Unix based open-source software (BSD licenced) written in Python.

  13. Molecular Toxicology of Substances Released from Resin–Based Dental Restorative Materials

    PubMed Central

    Bakopoulou, Athina; Papadopoulos, Triantafillos; Garefis, Pavlos

    2009-01-01

    Resin-based dental restorative materials are extensively used today in dentistry. However, significant concerns still remain regarding their biocompatibility. For this reason, significant scientific effort has been focused on the determination of the molecular toxicology of substances released by these biomaterials, using several tools for risk assessment, including exposure assessment, hazard identification and dose-response analysis. These studies have shown that substances released by these materials can cause significant cytotoxic and genotoxic effects, leading to irreversible disturbance of basic cellular functions. The aim of this article is to review current knowledge related to dental composites’ molecular toxicology and to give implications for possible improvements concerning their biocompatibility. PMID:19865523

  14. 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.

  15. 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.

  16. Molecular toxicology of substances released from resin-based dental restorative materials.

    PubMed

    Bakopoulou, Athina; Papadopoulos, Triantafillos; Garefis, Pavlos

    2009-09-04

    Resin-based dental restorative materials are extensively used today in dentistry. However, significant concerns still remain regarding their biocompatibility. For this reason, significant scientific effort has been focused on the determination of the molecular toxicology of substances released by these biomaterials, using several tools for risk assessment, including exposure assessment, hazard identification and dose-response analysis. These studies have shown that substances released by these materials can cause significant cytotoxic and genotoxic effects, leading to irreversible disturbance of basic cellular functions. The aim of this article is to review current knowledge related to dental composites' molecular toxicology and to give implications for possible improvements concerning their biocompatibility.

  17. Enzymic and molecular properties of base-plate parts of bacteriophage P22.

    PubMed

    Iwashita, S; Kanegasaki, S

    1976-05-17

    Using 14C-labeled Salmonella bacterial cells as the substrate, the enzymic and molecular properties of the base-plate parts of phage P22 were studied. The base-plate part consisted of a single protein species which cleaved extensively the O-antigen of Salmonella typhimurium, Salmonelly schottmuellerie and with somewhat slower rate that of Salmonella typhi, releasing oligo-saccharide products with rhamnose at the reducing end. Much less cleavage was observed with a strain of S. typhimurium lysogenic for P22, and no significant reaction with Salmonella anatum, Salmonella newington and Salmonella minneapolis. The base-plate part enzyme was a very heat-stable protein and only 10-20% loss was observed after treatment at 85 degrees C for 5 min. The pH optimum of the enzyme was around 7.5, and the glycosidase activity was not influenced by the ionic strength (25-250 mM( of the medium or the presence of Mg2+. The molecular weight of the base-plate part was 320,000 by sedimentation equilibrium. Dodecylsulphate-acrylamide gel electrophoresis revealed a single band of molecular weight 77,000, indicating that a single base-plate part corresponds to a tetramer of identical subunits. Circular dichroism spectra of P22 base-plate parts showed a major contribution of beta structure. The protein was rich in acidic amino acids, glycine and serine.

  18. Luminescence-based Imaging Approaches in the Field of Interventional Molecular Imaging.

    PubMed

    van Leeuwen, Fijs W B; Hardwick, James C H; van Erkel, Arian R

    2015-07-01

    Luminescence imaging-based guidance technologies are increasingly gaining interest within surgical and radiologic disciplines. Their promise to help visualize molecular features of disease in real time and with microscopic detail is considered desirable. Integrating luminescence imaging with three-dimensional radiologic- and/or nuclear medicine-based preinterventional imaging may overcome limitations such as the limited tissue penetration of luminescence signals. At the same time, the beneficial features of luminescence imaging may be used to complement the routinely used radiologic- and nuclear medicine-based modalities. To fully exploit this integrated concept, and to relate the largely experimental luminesce-based guidance approaches into perspective with routine imaging approaches, it is essential to understand the advantages and limitations of this relatively new modality. By providing an overview of the available luminescence technologies and the various clinically evaluated exogenous luminescent tracers (fluorescent, hybrid, and theranostic tracers), this review attempts to place luminescence-based interventional molecular imaging technologies into perspective to the available radiologic- and/or nuclear medicine-based imaging technologies. At the same time, the transition from anatomic to physiologic and even molecular interventional luminescence imaging is illustrated.

  19. Molecular-based surveillance of campylobacteriosis in New Zealand--from source attribution to genomic epidemiology.

    PubMed

    Muellner, P; Pleydell, E; Pirie, R; Baker, M G; Campbell, D; Carter, P E; French, N P

    2013-01-17

    Molecular-based surveillance of campylobacteriosis in New Zealand contributed to the implementation of interventions that led to a 50% reduction in notified and hospitalised cases of the country's most important zoonosis. From a pre-intervention high of 384 per 100,000 population in 2006, incidence dropped by 50% in 2008; a reduction that has been sustained since. This article illustrates many aspects of the successful use of molecular-based surveillance, including the distinction between control-focused and strategy-focused surveillance and advances in source attribution. We discuss how microbial genetic data can enhance the understanding of epidemiological explanatory and response variables and thereby enrich the epidemiological analysis. Sequence data can be fitted to evolutionary and epidemiological models to gain new insights into pathogen evolution, the nature of associations between strains of pathogens and host species, and aspects of between-host transmission. With the advent of newer sequencing technologies and the availability of rapid, high-coverage genome sequence data, such techniques may be extended and refined within the emerging discipline of genomic epidemiology. The aim of this article is to summarise the experience gained in New Zealand with molecular-based surveillance of campylobacteriosis and to discuss how this experience could be used to further advance the use of molecular tools in surveillance.

  20. Gold-based hybrid nanomaterials for biosensing and molecular diagnostic applications.

    PubMed

    Kim, Jung Eun; Choi, Ji Hye; Colas, Marion; Kim, Dong Ha; Lee, Hyukjin

    2016-06-15

    The properties of gold nanomaterials are particularly of interest to many researchers, since they show unique physiochemical properties such as optical adsorption of specific wavelength of light, high electrical conductance with rich surface electrons, and facile surface modification with sulfhydryl groups. These properties have facilitated the use of gold nanomaterials in the development of various hybrid systems for biosensors and molecular diagnostics. Combined with various synthetic materials such as fluorescence dyes, polymers, oligonucleotides, graphene oxides (GO), and quantum dots (QDs), the gold-based hybrid nanomaterials offer multi-functionalities in molecular detection with high specificity and sensitivity. These two aspects result in the increase of detection speed as well as the lower detection limits, having shown that this diagnosis method is more effective than other conventional ones. In this review, we have highlighted various examples of nanomaterials for biosensing and molecular diagnostics. The gold-based hybrid systems are categorized by three distinct detection approaches, in which include (1) optical, such as surface plasmon resonance (SPR), RAMAN, and surface-enhanced Raman scattering (SERS), (2) fluorescence, such as förster resonance energy transfer (FRET) and nanomaterial surface energy transfer (NSET), and (3) electrochemical, such as potentiometic, amperometric, and conductometric. Each example provides the detailed mechanism of molecular detection as well as the supporting experimental result with the limit of detection (LOD). Lastly, future perspective on novel development of gold-based hybrid nanomaterials is discussed as well as their challenges.

  1. Synchrotron-based and globar-sourced molecular (micro)spectroscopy contributions to advances in new hulless barley (with structure alteration) research on molecular structure, molecular nutrition, and nutrient delivery.

    PubMed

    Yang, Ling; Yu, Peiqiang

    2017-01-02

    This paper aimed to review synchrotron-based and globar-sourced molecular infrared (micro)spectroscopy contributions to advances in new hulless barley (with structure alteration) research on molecular structure, molecular nutrition, and nutrient delivery in ruminants. It reviewed recent progress in barley varieties, its utilization for animal and human, inherent structure features and chemical make-up, evaluation and research methodology, breeding progress, rumen degradation, and intestinal digestion. The emphasis of this review was focused on the effect of alteration of carbohydrate traits of newly developed hulless barley on molecular structure changes and nutrient delivery and quantification of the relationship between molecular structure features and changes and truly absorbed nutrient supply to ruminants. This review provides an insight into how inherent structure changes on a molecular basis affect nutrient utilization and availability in ruminants.

  2. Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites.

    PubMed

    Floros, Dimitrios J; Petras, Daniel; Kapono, Clifford A; Melnik, Alexey V; Ling, Tie-Jun; Knight, Rob; Dorrestein, Pieter C

    2017-01-01

    Plants play an essential part in global carbon fixing through photosynthesis and are the primary food and energy source for humans. Understanding them thoroughly is therefore of highest interest for humanity. Advances in DNA and RNA sequencing and in protein and metabolite analysis allow the systematic description of plant composition at the molecular level. With imaging mass spectrometry, we can now add a spatial level, typically in the micrometer-to-centimeter range, to their compositions, essential for a detailed molecular understanding. Here we present an LC-MS based approach for 3D plant imaging, which is scalable and allows the analysis of entire plants. We applied this approach in a case study to pepper and tomato plants. Together with MS/MS spectra library matching and spectral networking, this non-targeted workflow provides the highest sensitivity and selectivity for the molecular annotations and imaging of plants, laying the foundation for studies of plant metabolism and plant-environment interactions.

  3. A Cobalt Supramolecular Triple-Stranded Helicate-based Discrete Molecular Cage

    PubMed Central

    Mai, Hien Duy; Kang, Philjae; Kim, Jin Kyung; Yoo, Hyojong

    2017-01-01

    We report a strategy to achieve a discrete cage molecule featuring a high level of structural hierarchy through a multiple-assembly process. A cobalt (Co) supramolecular triple-stranded helicate (Co-TSH)-based discrete molecular cage (1) is successfully synthesized and fully characterized. The solid-state structure of 1 shows that it is composed of six triple-stranded helicates interconnected by four linking cobalt species. This is an unusual example of a highly symmetric cage architecture resulting from the coordination-driven assembly of metallosupramolecular modules. The molecular cage 1 shows much higher CO2 uptake properties and selectivity compared with the separate supramolecular modules (Co-TSH, complex 2) and other molecular platforms. PMID:28262690

  4. [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.

  5. Ionic Conductivity Trends with Molecular Weight in PEO and PEO-Based Solid Polymer Electrolytes

    NASA Astrophysics Data System (ADS)

    Teran, Alexander; Mullin, Scott; Wanakule, Nisita; Panday, Ashoutosh; Balsara, Nitash

    2010-03-01

    Poly(ethylene oxide) based polymer electrolytes with lithium bis(trifluoromethane)sulfonamide (LiTFSI) salt remain one of the most promising class of solid polymer electrolyte for rechargeable lithium metal batteries. Among those, poly(styrene-b-ethyleneoxide) (SEO) doped with LiTFSI has been shown to exhibit acceptable levels of conductivity while possessing a sufficiently high modulus to suppress the growth of dendrites. The purpose of this study is to explore the molecular weight dependence on conductivity for the PEO/LiTFSI system to which previous studies have alluded, but never quantified, and contrast this with the observed molecular weight dependence of SEO reported in previous work. Conductivities were measured using AC impedance spectroscopy over a broad range of temperatures and molecular weights beyond those reported in the literature.

  6. Construction of a Chassis for a Tripartite Protein-Based Molecular Motor.

    PubMed

    Small, Lara S R; Bruning, Marc; Thomson, Andrew R; Boyle, Aimee L; Davies, Roberta B; Curmi, Paul M G; Forde, Nancy R; Linke, Heiner; Woolfson, Derek N; Bromley, Elizabeth H C

    2017-03-14

    Improving our understanding of biological motors, both to fully comprehend their activities in vital processes, and to exploit their impressive abilities for use in bionanotechnology, is highly desirable. One means of understanding these systems is through the production of synthetic molecular motors. We demonstrate the use of orthogonal coiled-coil dimers (including both parallel and antiparallel coiled coils) as a hub for linking other components of a previously described synthetic molecular motor, the Tumbleweed. We use circular dichroism, analytical ultracentrifugation, dynamic light scattering, and disulfide rearrangement studies to demonstrate the ability of this six-peptide set to form the structure designed for the Tumbleweed motor. The successful formation of a suitable hub structure is both a test of the transferability of design rules for protein folding as well as an important step in the production of a synthetic protein-based molecular motor.

  7. Molecular drag model based on differential reduction of the Kruger-Shapiro equations

    NASA Astrophysics Data System (ADS)

    Helmer, J. C.; Levi, G.

    2002-07-01

    The history of the method of differential probability in molecular flow is reviewed, beginning with the little known derivation by D. Santeler (5th Annual Symposium on Space Environmental Simulation, Arnold Air Force Station, TN, May, 1964), based on the equation of C. W. Oatley [Br. J. Appl. Phys. 8, 15 (1957)]. This method contains the aperture correction within the theory, without phenomenological assumptions. A new equation of this type, for molecular pumping, is derived by differential reduction of the Kruger-Shapiro equations. A simple solution of the differential equations yields results of good accuracy for engineering use. The physical characteristics of molecular pumping are clarified by describing the pressure distribution within the pumping tube as if it were a conductance. By this method the calculated performance of a model pump is shown to be in satisfactory agreement with a Clausing-type solution from a previous publication. copyright 2002 American Vacuum Society.

  8. De novo design of novel DNA-gyrase inhibitors based on 2D molecular fingerprints.

    PubMed

    Huang, Zhengui; Lin, Kejiang; You, Qidong

    2013-07-15

    As increasing drug-resistance poses an emerging threat to public health, the development of novel antibacterial agents is critical. We developed a workflow consisting of various methods for de novo design. In the workflow, 2D-QSAR model based on molecular fingerprints was constructed to extract the bioactive molecular fingerprints from a data set of DNA-gyrase inhibitors with new structure and mechanism. These fingerprints were converted into molecular fragments which were recombined to generate compound library. The new compound library was virtually screened by LigandFit and Gold docking, and the results were further investigated by pharmacophore validation and binding mode analysis. The workflow successfully achieved a potential DNA-gyrase inhibitor. It could be applied to design more novel potential DNA-gyrase inhibitors and provide theoretical basis for further optimization of the hit compounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. 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

  10. 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

    2016-01-04

    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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. HDR-del: A tool based on Hamming distance for prioritizing pathogenic chromosomal deletions in exome sequencing.

    PubMed

    Imai, Atsuko; Kohda, Masakazu; Kobayashi, Kaori; Hirata, Tomoko; Sakata, Yasushi; Murayama, Kei; Ohtake, Akira; Okazaki, Yasushi; Nakaya, Akihiro; Ott, Jurg

    2017-07-19

    High-density oligonucleotide arrays have been widely used to detect pathogenic chromosomal deletions. In addition to high-density oligonucleotide arrays, programs using whole exome sequencing have become available for estimating copy number variations using depth of coverage. Here we propose a new statistical method, HDR-del, to prioritize pathogenic chromosomal deletions based on Hamming distance in exome sequencing. In vcf (Variant Call Format) files generated from exome sequencing, hemizygous chromosomal deletion regions lack heterozygous variants and lead to apparent long runs of homozygosity (ROH). In our HDR-del approach, we calculate the "difference" in heterozygous status between an affected individual and control individuals using the Hamming Distance Ratio (HDR) over all candidate chromosomal deletion regions defined as ROH longer than 1Mbp. Using a suitable test statistic, which is expected to be large for a true pathogenic deletion region, we prioritize candidate chromosomal deletion regions based on this statistic. In our approach, we were able to considerably narrow down true pathogenic chromosomal deletion regions, which were confirmed by high-density oligonucleotide arrays in four mitochondrial disease patients. Our HDR-del approach represents an easy method for detecting chromosomal deletions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Hierarchical QSAR technology based on the Simplex representation of molecular structure

    NASA Astrophysics Data System (ADS)

    Kuz'min, V. E.; Artemenko, A. G.; Muratov, E. N.

    2008-06-01

    This article is about the hierarchical quantitative structure-activity relationship technology (HiT QSAR) based on the Simplex representation of molecular structure (SiRMS) and its application for different QSAR/QSP(property)R tasks. The essence of this technology is a sequential solution (with the use of the information obtained on the previous steps) to the QSAR problem by the series of enhanced models of molecular structure description [from one dimensional (1D) to four dimensional (4D)]. It is a system of permanently improved solutions. 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 detailing increases consecutively from the 1D to 4D representation of the molecular structure. The advantages of the approach reported here are the absence of "molecular alignment" problems, consideration of different physical-chemical properties of atoms (e.g. charge, lipophilicity, etc.), the high adequacy and good interpretability of obtained models and clear ways for molecular design. The efficiency of the HiT QSAR approach is demonstrated by comparing it 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 predictive virtual screening tools and their ability to serve as the base of directed drug design was validated by subsequent synthetic and biological experiments, among others. The HiT QSAR is realized as a complex of computer programs known as HiT QSAR software that also includes a powerful statistical block and a number of useful utilities.

  13. A Formaldehyde Sensor Based on Molecularly-Imprinted Polymer on a TiO₂ Nanotube Array.

    PubMed

    Tang, Xiaohui; Raskin, Jean-Pierre; Lahem, Driss; Krumpmann, Arnaud; Decroly, André; Debliquy, Marc

    2017-03-24

    Today, significant attention has been brought to the development of sensitive, specific, cheap, and reliable sensors for real-time monitoring. Molecular imprinting technology is a versatile and promising technology for practical applications in many areas, particularly chemical sensors. Here, we present a chemical sensor for detecting formaldehyde, a toxic common indoor pollutant gas. Polypyrrole-based molecularly-imprinted polymer (PPy-based MIP) is employed as the sensing recognition layer and synthesized on a titanium dioxide nanotube array (TiO₂-NTA) for increasing its surface-to-volume ratio, thereby improving the sensor performance. Our sensor selectively detects formaldehyde in the parts per million (ppm) range at room temperature. It also shows a long-term stability and small fluctuation to humidity variations. These are attributed to the thin fishnet-like structure of the PPy-based MIP on the highly-ordered and vertically-aligned TiO₂-NTA.

  14. 3D-Lab: a collaborative web-based platform for molecular modeling.

    PubMed

    Grebner, Christoph; Norrby, Magnus; Enström, Jonatan; Nilsson, Ingemar; Hogner, Anders; Henriksson, Jonas; Westin, Johan; Faramarzi, Farzad; Werner, Philip; Boström, Jonas

    2016-09-01

    The use of 3D information has shown impact in numerous applications in drug design. However, it is often under-utilized and traditionally limited to specialists. We want to change that, and present an approach making 3D information and molecular modeling accessible and easy-to-use 'for the people'. A user-friendly and collaborative web-based platform (3D-Lab) for 3D modeling, including a blazingly fast virtual screening capability, was developed. 3D-Lab provides an interface to automatic molecular modeling, like conformer generation, ligand alignments, molecular dockings and simple quantum chemistry protocols. 3D-Lab is designed to be modular, and to facilitate sharing of 3D-information to promote interactions between drug designers. Recent enhancements to our open-source virtual reality tool Molecular Rift are described. The integrated drug-design platform allows drug designers to instantaneously access 3D information and readily apply advanced and automated 3D molecular modeling tasks, with the aim to improve decision-making in drug design projects.

  15. Molecular and cellular bases of adaptation to a changing environment in microorganisms

    PubMed Central

    Bleuven, Clara

    2016-01-01

    Environmental heterogeneity constitutes an evolutionary challenge for organisms. While evolutionary dynamics under variable conditions has been explored for decades, we still know relatively little about the cellular and molecular mechanisms involved. It is of paramount importance to examine these molecular bases because they may play an important role in shaping the course of evolution. In this review, we examine the diversity of adaptive mechanisms in the face of environmental changes. We exploit the recent literature on microbial systems because those have benefited the most from the recent emergence of genetic engineering and experimental evolution followed by genome sequencing. We identify four emerging trends: (i) an adaptive molecular change in a pathway often results in fitness trade-off in alternative environments but the effects are dependent on a mutation's genetic background; (ii) adaptive changes often modify transcriptional and signalling pathways; (iii) several adaptive changes may occur within the same molecular pathway but be associated with pleiotropy of different signs across environments; (iv) because of their large associated costs, macromolecular changes such as gene amplification and aneuploidy may be a rapid mechanism of adaptation in the short-term only. The course of adaptation in a variable environment, therefore, depends on the complexity of the environment but also on the molecular relationships among the genes involved and between the genes and the phenotypes under selection. PMID:27798299

  16. 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.

  17. In silico modelling and molecular dynamics simulation studies of thiazolidine based PTP1B inhibitors.

    PubMed

    Mahapatra, Manoj Kumar; Bera, Krishnendu; Singh, Durg Vijay; Kumar, Rajnish; Kumar, Manoj

    2017-04-21

    Protein tyrosine phosphatase 1B (PTP1B) has been identified as a negative regulator of insulin and leptin signalling pathway; hence, it can be considered as a new therapeutic target of intervention for the treatment of type 2 diabetes. Inhibition of this molecular target takes care of both diabetes and obesity, i.e. diabestiy. In order to get more information on identification and optimization of lead, pharmacophore modelling, atom-based 3D QSAR, docking and molecular dynamics studies were carried out on a set of ligands containing thiazolidine scaffold. A six-point pharmacophore model consisting of three hydrogen bond acceptor (A), one negative ionic (N) and two aromatic rings (R) with discrete geometries as pharmacophoric features were developed for a predictive 3D QSAR model. The probable binding conformation of the ligands within the active site was studied through molecular docking. The molecular interactions and the structural features responsible for PTP1B inhibition and selectivity were further supplemented by molecular dynamics simulation study for a time scale of 30 ns. The present investigation has identified some of the indispensible structural features of thiazolidine analogues which can further be explored to optimize PTP1B inhibitors.

  18. 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

  19. 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.

  20. Molecular dating of phylogenetic divergence between Urochloa species based on complete chloroplast genomes.

    PubMed

    Pessoa-Filho, Marco; Martins, Alexandre Magalhães; Ferreira, Márcio Elias

    2017-07-06

    Forage species of Urochloa are planted in millions of hectares of tropical and subtropical pastures in South America. Most of the planted area is covered with four species (U. ruziziensis, U. brizantha, U. decumbens and U. humidicola). Breeding programs rely on interspecific hybridizations to increase genetic diversity and introgress traits of agronomic importance. Knowledge of phylogenetic relationships is important to optimize compatible hybridizations in Urochloa, where phylogeny has been subject of some controversy. We used next-generation sequencing to assemble the chloroplast genomes of four Urochloa species to investigate their phylogenetic relationships, compute their times of divergence and identify chloroplast DNA markers (microsatellites, SNPs and InDels). Whole plastid genome sizes were 138,765 bp in U. ruziziensis, 138,945 bp in U. decumbens, 138,946 bp in U. brizantha and 138,976 bp in U. humidicola. Each Urochloa chloroplast genome contained 130 predicted coding regions and structural features that are typical of Panicoid grasses. U. brizantha and U. decumbens chloroplast sequences are highly similar and show reduced SNP, InDel and SSR polymorphism as compared to U. ruziziensis and U. humidicola. Most of the structural and sequence polymorphisms were located in intergenic regions, and reflected phylogenetic distances between species. Divergence of U. humidicola from a common ancestor with the three other Urochloa species was estimated at 9.46 mya. U. ruziziensis, U. decumbens, and U. brizantha formed a clade where the U. ruziziensis lineage would have diverged by 5.67 mya, followed by a recent divergence event between U. decumbens and U. brizantha around 1.6 mya. Low-coverage Illumina sequencing allowed the successful sequence analysis of plastid genomes in four species of Urochloa used as forages in the tropics. Pairwise sequence comparisons detected multiple microsatellite, SNP and InDel sites prone to be used as molecular markers in genetic

  1. Grid-based continual analysis of molecular interior for drug discovery, QSAR and QSPR.

    PubMed

    Potemkin, A V; Grishina, M A; Potemkin, V A

    2017-02-07

    In 1979, R.D.Cramer and M.Milne made a first realization of the above mentioned principles attempting to compare molecules by aligning them in space and by mapping their molecular fields to a 3D grid. Further, this approach was developed as the DYLOMMS (DYnamic Lattice-Oriented Molecular Modelling System) approach. In 1984, H.Wold and S.Wold proposed the use of partial least squares (PLS) analysis, instead of principal component analysis, to correlate the field values with biological activities. Then, in 1988 the method which was called CoMFA (Comparative Molecular Field Analysis) was introduced and the appropriate software became commercially available. Since 1988, a lot of 3D QSAR methods, algorithms and their modifications are introduced for solving of virtual drug discovery problems (e.g., CoMSIA, CoMMA, HINT, HASL, GOLPE, GRID, PARM, Raptor, BiS, CiS, ConGO,). All the methods can be divided into two groups (classes):1. Methods studying the exterior of molecules; 2) Methods studying the interior of molecules. A series of grid-based computational technologies for Continual Molecular Interior analysis (CoMIn) is invented in the current paper. The grid-based analysis is fulfilled by means of a lattice construction analogously to many other grid-based methods. The further continual elucidation of molecular structure is performed in various ways. (i) In the terms of intermolecular interactions potentials. This can be represented as a superposition of Coulomb, Van der Waals interactions and hydrogen bonds. All the potentials are well known continual functions and their values can be determined in all lattice points for a molecule. (ii) In the terms of quantum functions such as electron density distribution, Laplacian and Hamiltonian of electron density distribution, potential energy distribution, the highest occupied and the lowest unoccupied molecular orbitals distribution and their superposition. To reduce time of calculations using quantum methods based on the

  2. Responsive small molecular hydrogels based on adamantane-peptides for cell culture.

    PubMed

    Yang, Cuihong; Li, Dongxia; Liu, Zheng; Hong, Ge; Zhang, Jun; Kong, Deling; Yang, Zhimou

    2012-01-12

    The development of responsive small molecular hydrogels that can be applied for recovery of cells postculture attract extensive interests for researchers in fields of cell biology, stem cell differentiation, and tissue engineering. We report in this study several responsive small molecular hydrogels based on adamantane-peptides whose gel to clear solution phase transition can be achieved by addition of β-cyclodextrin (β-CD) derivatives. The small molecular hydrogels are formed by our recently developed method of disulfide bond cleavage by glutathione (GSH). Mouse fibroblast 3T3 cells attach and grow well at the surface of hydrogels. Furthermore, 3T3 cells postculture can be recovered from the gels by the addition of a β-CD derivative due to formation of clear solutions by the adamantane-β-CD interaction. The culture on hydrogels and recovery process do not cause obvious effects on behaviors of 3T3 cells. The results shown in this study indicate that small molecular hydrogels based on adamantane-peptides have great potentials in research fields where further analysis of cells is needed.

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

    PubMed

    Ahn, Byeong-Cheol

    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.

  4. Pre-examination factors affecting molecular diagnostic test results and interpretation: A case-based approach.

    PubMed

    Payne, Deborah A; Baluchova, Katarina; Peoc'h, Katell H; van Schaik, Ron H N; Chan, K C Allen; Maekawa, Masato; Mamotte, Cyril; Russomando, Graciela; Rousseau, François; Ahmad-Nejad, Parviz

    2017-04-01

    Multiple organizations produce guidance documents that provide opportunities to harmonize quality practices for diagnostic testing. The International Organization for Standardization ISO 15189 standard addresses requirements for quality in management and technical aspects of the clinical laboratory. One technical aspect addresses the complexities of the pre-examination phase prior to diagnostic testing. The Committee for Molecular Diagnostics of the International Federation for Clinical Chemistry and Laboratory Medicine (also known as, IFCC C-MD) conducted a survey of international molecular laboratories and determined ISO 15189 to be the most referenced guidance document. In this review, the IFCC C-MD provides case-based examples illustrating the value of select pre-examination processes as these processes relate to molecular diagnostic testing. Case-based examples in infectious disease, oncology, inherited disease and pharmacogenomics address the utility of: 1) providing information to patients and users, 2) designing requisition forms, 3) obtaining informed consent and 4) maintaining sample integrity prior to testing. The pre-examination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. The clinical vignettes presented in this paper illustrate the value of applying select ISO 15189 recommendations for general laboratory to the more specialized area of Molecular Diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Computational molecular design of polyhedral oligomeric silsesquioxane based organic-inorganic hybrid semiconductors

    NASA Astrophysics Data System (ADS)

    Qi, Feng

    Cubic silsesquioxanes (T8 SQs), with the formula of [RSiO1.5] 8, enable advanced materials design. In this thesis, a computational materials science framework, including ab initio density functional theory (DFT) calculations, molecular dynamics (MD), and Monte Carlo (MC) simulations, was developed to perform computational molecular design and crystal engineering of silsesquioxane based diacene-SQ and then octa(halogenphenyl)-SQ molecular systems. The goal of this project was to identify novel molecular architectures, a priori, that exhibit targeted self-assembly behaviors and result in materials with improved electronic properties. First, existing force fields, including our in house charge transfer reactive (CTR) force field, and COMPASS, were evaluated for simulating cubic silsesquioxane systems. All force fields reproduced the experimental structure of SQ-based crystals very well. However, only the FLX force field reproduced the experimentally observed vibrational properties and thermodynamic behavior. Next, targeting materials performance, such as high electronic mobility, a series of diacene-SQ molecules were designed and their crystal structures predicted by following the computational molecular design recipe that accounts for transport theory, symmetry relationships, polymorph prediction procedures, and solid state electronic property evaluation methods. Computationally derived diacene-SQ crystals are predicted to exhibit advanced electronic properties, such as very small band gaps and parallel packing of the acene groups in crystal structures, indicating excellent transport properties, as well as improved thermal and mechanical properties. Finally, a series of new small-band gap octa(halogenphenyl)-SQ molecular systems were identified by computationally exploring alternative architectures and functionalization of recently synthesized octa(halogenphenyl)-SQ crystals. These hybrid molecular crystals also feature other unique properties, such as solution

  6. 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.

  7. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Contemporary nucleic acid-based molecular techniques for detection, identification, and characterization of Bifidobacterium.

    PubMed

    Mianzhi, Yao; Shah, Nagendra P

    2017-03-24

    Bifidobacteria are one of the most important bacterial groups found in the gastrointestinal tract of humans. Medical and food industry researchers have focused on bifidobacteria because of their health-promoting properties. Researchers have historically relied on classic phenotypic approaches (culture and biochemical tests) for detection and identification of bifidobacteria. Those approaches still have values for the identification and detection of some bifidobacterial species, but they are often labor-intensive and time-consuming and can be problematic in differentiating closely related species. Rapid, accurate, and reliable methods for detection, identification, and characterization of bifidobacteria in a mixed bacterial population have become a major challenge. The advent of nucleic acid-based molecular techniques has significantly advanced isolation and detection of bifidobacteria. Diverse nucleic acid-based molecular techniques have been employed, including hybridization, target amplification, and fingerprinting. Certain techniques enable the detection, characterization, and identification at genus-, species-, and strains-levels, whereas others allow typing of species or strains of bifidobacteria. In this review, an overview of methodological principle, technique complexity, and application of various nucleic acid-based molecular techniques for detection, identification, and characterization of bifidobacteria is presented. Advantages and limitations of each technique are discussed, and significant findings based on particular techniques are also highlighted.

  9. Photoelectrochemical sensor for pentachlorophenol on microfluidic paper-based analytical device based on the molecular imprinting technique.

    PubMed

    Sun, Guoqiang; Wang, Panpan; Ge, Shenguang; Ge, Lei; Yu, Jinghua; Yan, Mei

    2014-06-15

    Combining microfluidic paper-based analytical device (μ-PAD) and the molecular imprinting technique, a visible light photoelectrochemical (PEC) sensing platform for the detection of pentachlorophenol (PCP) was established on gold nanoparticles (AuNPs) decorated paper working electrode using polypyrrole-functionalized ZnO nanoparticles. Ascorbic acid (AA) was exploited as an efficient and nontoxic electron donor for scavenging photogenerated holes under mild solution medium and facilitating the generation of stable photocurrent. The microfluidic molecular imprinted polymer-based PEC analytical origami device is developed for the detection of PCP in the linear range from 0.01 ng mL(-1) to 100 ng mL(-1) with a low detection limit of 4 pg mL(-1). This disposable microfluidic PEC origami device would provide a new platform for sensitive, specific, and multiplex assay in public health, environmental monitoring, and the developing world.

  10. Molecular electronic devices based on single-walled carbon nanotube electrodes.

    PubMed

    Feldman, Alina K; Steigerwald, Michael L; Guo, Xuefeng; Nuckolls, Colin

    2008-12-01

    As the top-down fabrication techniques for silicon-based electronic materials have reached the scale of molecular lengths, researchers have been investigating nanostructured materials to build electronics from individual molecules. Researchers have directed extensive experimental and theoretical efforts toward building functional optoelectronic devices using individual organic molecules and fabricating metal-molecule junctions. Although this method has many advantages, its limitations lead to large disagreement between experimental and theoretical results. This Account describes a new method to create molecular electronic devices, covalently bridging a gap in a single-walled carbon nanotube (SWNT) with an electrically functional molecule. First, we introduce a molecular-scale gap into a nanotube by precise oxidative cutting through a lithographic mask. Now functionalized with carboxylic acids, the ends of the cleaved carbon nanotubes are reconnected with conjugated diamines to give robust diamides. The molecular electronic devices prepared in this fashion can withstand and respond to large environmental changes based on the functional groups in the molecules. For example, with oligoanilines as the molecular bridge, the conductance of the device is sensitive to pH. Similarly, using diarylethylenes as the bridge provides devices that can reversibly switch between conjugated and nonconjugated states. The molecular bridge can perform the dual task of carrying electrical current and sensing/recognition through biological events such as protein/substrate binding and DNA hybridization. The devices based on DNA can measure the difference in electrical properties of complementary and mismatched strands. A well-matched duplex DNA 15-mer in the gap exhibits a 300-fold lower resistance than a duplex with a GT or CA mismatch. This system provides an ultrasensitive way to detect single-nucleotide polymorphisms at the individual molecule level. Restriction enzymes can cleave

  11. 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.

  12. 3D-QSAR, molecular docking, and molecular dynamic simulations for prediction of new Hsp90 inhibitors based on isoxazole scaffold.

    PubMed

    Abbasi, Maryam; Sadeghi-Aliabadi, Hojjat; Amanlou, Massoud

    2017-05-24

    Heat shock protein 90(Hsp90), as a molecular chaperone, play a crucial role in folding and proper function of many proteins. Hsp90 inhibitors containing isoxazole scaffold are currently being used in the treatment of cancer as tumor suppressers. Here in the present studies, new compounds based on isoxazole scaffold were predicted using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamic (MD) simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were also done. The steric and electrostatic contour map of CoMFA and CoMSIA were created. Hydrophobic, hydrogen bond donor and acceptor of CoMSIA model also were generated, and new compounds were predicted by CoMFA and CoMSIA contour maps. To investigate the binding modes of the predicted compounds in the active site of Hsp90, a molecular docking simulation was carried out. MD simulations were also conducted to evaluate the obtained results on the best predicted compound and the best reported Hsp90 inhibitors in the 3D-QSAR model. Findings indicate that the predicted ligands were stable in the active site of Hsp90.

  13. Capturing molecular multimode relaxation processes in excitable gases based on decomposition of acoustic relaxation spectra

    NASA Astrophysics Data System (ADS)

    Zhu, Ming; Liu, Tingting; Wang, Shu; Zhang, Kesheng

    2017-08-01

    Existing two-frequency reconstructive methods can only capture primary (single) molecular relaxation processes in excitable gases. In this paper, we present a reconstructive method based on the novel decomposition of frequency-dependent acoustic relaxation spectra to capture the entire molecular multimode relaxation process. This decomposition of acoustic relaxation spectra is developed from the frequency-dependent effective specific heat, indicating that a multi-relaxation process is the sum of the interior single-relaxation processes. Based on this decomposition, we can reconstruct the entire multi-relaxation process by capturing the relaxation times and relaxation strengths of N interior single-relaxation processes, using the measurements of acoustic absorption and sound speed at 2N frequencies. Experimental data for the gas mixtures CO2-N2 and CO2-O2 validate our decomposition and reconstruction approach.

  14. Recent emergence of photon upconversion based on triplet energy migration in molecular assemblies.

    PubMed

    Yanai, Nobuhiro; Kimizuka, Nobuo

    2016-04-07

    An emerging field of triplet energy migration-based photon upconversion (TEM-UC) is reviewed. Highly efficient photon upconversion has been realized in a wide range of chromophore assemblies, such as non-solvent liquids, ionic liquids, amorphous solids, gels, supramolecular assemblies, molecular crystals, and metal-organic frameworks (MOFs). The control over their assembly structures allows for unexpected air-stability and maximum upconversion quantum yield at weak solar irradiance that has never been achieved by the conventional molecular diffusion-based mechanism. The introduction of the "self-assembly" concept offers a new perspective in photon upconversion research and triplet exciton science, which show promise for numerous applications ranging from solar energy conversion to chemical biology.

  15. All-Carbon Electrode Molecular Electronic Devices Based on Langmuir-Blodgett Monolayers.

    PubMed

    Sangiao, Soraya; Martín, Santiago; González-Orive, Alejandro; Magén, César; Low, Paul J; De Teresa, José M; Cea, Pilar

    2017-02-01

    Nascent molecular electronic devices, based on monolayer Langmuir-Blodgett films sandwiched between two carbonaceous electrodes, have been prepared. Tightly packed monolayers of 4-((4-((4-ethynylphenyl)ethynyl)phenyl)ethynyl)benzoic acid are deposited onto a highly oriented pyrolytic graphite electrode. An amorphous carbon top contact electrode is formed on top of the monolayer from a naphthalene precursor using the focused electron beam induced deposition technique. This allows the deposition of a carbon top-contact electrode with well-defined shape, thickness, and precise positioning on the film with nm resolution. These results represent a substantial step toward the realization of integrated molecular electronic devices based on monolayers and carbon electrodes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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.

  17. United-Atom Discrete Molecular Dynamics of Proteins Using Physics-Based Potentials.

    PubMed

    Emperador, Agustí; Meyer, Tim; Orozco, Modesto

    2008-12-09

    We present a method for the efficient simulation of the equilibrium dynamics of proteins based on the well established discrete molecular dynamics algorithm, which avoids integration of Newton equations of motion at short time steps, allowing then the derivation of very large trajectories for proteins with a reduced computational cost. In the presented implementation we used an all heavy-atoms description of proteins, with simple potentials describing the conformational region around the experimental structure based on local physical interactions (covalent structure, hydrogen bonds, hydrophobic contacts, solvation, steric hindrance, and bulk dispersion interactions). The method shows a good ability to describe the flexibility of 33 diverse proteins in water as determined by atomistic molecular dynamics simulation and can be useful for massive simulation of proteins in crowded environments or for refinement of protein structure in large complexes.

  18. 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.

  19. 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.

  20. Modeling the relationship between body weight and energy intake: A molecular diffusion-based approach

    PubMed Central

    2012-01-01

    Background Body weight is at least partly controlled by the choices made by a human in response to external stimuli. Changes in body weight are mainly caused by energy intake. By analyzing the mechanisms involved in food intake, we considered that molecular diffusion plays an important role in body weight changes. We propose a model based on Fick's second law of diffusion to simulate the relationship between energy intake and body weight. Results This model was applied to food intake and body weight data recorded in humans; the model showed a good fit to the experimental data. This model was also effective in predicting future body weight. Conclusions In conclusion, this model based on molecular diffusion provides a new insight into the body weight mechanisms. Reviewers This article was reviewed by Dr. Cabral Balreira (nominated by Dr. Peter Olofsson), Prof. Yang Kuang and Dr. Chao Chen. PMID:22742862

  1. Performance Evaluation and Optimal Detection of Relay-Assisted Diffusion-Based Molecular Communication with Drift.

    PubMed

    Tavakkoli, Nooshin; Azmi, Paeiz; Mokari, Nader

    2016-11-16

    In this paper, we consider a decode-and-forward (DF) relay-assisted diffusion-based molecular communication system inside one of the blood vessels of a human body with positive drift from transmitter to receiver. We use the normal approximation to the distribution of the number of received molecules and derive a closed-form expression for the end-toend bit error probability of the system. We then propose an optimization problem that aims at minimizing the bit error probability of the system and solve it at the receiver nanomachine by an algorithm based on the bisection method to determine the optimal detection threshold. Furthermore, we study the impact of the system parameters, such as drift velocity, position of the relay node and number of allocated molecules on the performance of the system. The numerical results show that with a constant molecular budget, DF relying strategy can considerably improve the system performance.

  2. Extending rule-based methods to model molecular geometry and 3D model resolution.

    PubMed

    Hoard, Brittany; Jacobson, Bruna; Manavi, Kasra; Tapia, Lydia

    2016-08-01

    Computational modeling is an important tool for the study of complex biochemical processes associated with cell signaling networks. However, it is challenging to simulate processes that involve hundreds of large molecules due to the high computational cost of such simulations. Rule-based modeling is a method that can be used to simulate these processes with reasonably low computational cost, but traditional rule-based modeling approaches do not include details of molecular geometry. The incorporation of geometry into biochemical models can more accurately capture details of these processes, and may lead to insights into how geometry affects the products that form. Furthermore, geometric rule-based modeling can be used to complement other computational methods that explicitly represent molecular geometry in order to quantify binding site accessibility and steric effects. We propose a novel implementation of rule-based modeling that encodes details of molecular geometry into the rules and binding rates. We demonstrate how rules are constructed according to the molecular curvature. We then perform a study of antigen-antibody aggregation using our proposed method. We simulate the binding of antibody complexes to binding regions of the shrimp allergen Pen a 1 using a previously developed 3D rigid-body Monte Carlo simulation, and we analyze the aggregate sizes. Then, using our novel approach, we optimize a rule-based model according to the geometry of the Pen a 1 molecule and the data from the Monte Carlo simulation. We use the distances between the binding regions of Pen a 1 to optimize the rules and binding rates. We perform this procedure for multiple conformations of Pen a 1 and analyze the impact of conformation and resolution on the optimal rule-based model. We find that the optimized rule-based models provide information about the average steric hindrance between binding regions and the probability that antibodies will bind to these regions. These optimized models

  3. Model of molecular bonding based on the Bohr Sommerfeld picture of atoms

    NASA Astrophysics Data System (ADS)

    Svidzinsky, Anatoly A.; Chin, Siu A.; Scully, Marlan O.

    2006-07-01

    We develop a model of molecular binding based on the Bohr Sommerfeld description of atoms together with a constraint taken from conventional quantum mechanics. The model can describe the binding energy curves of H2, H3 and other molecules with striking accuracy. Our approach treats electrons as point particles with positions determined by extrema of an algebraic energy function. Our constrained model provides a physically appealing, accurate description of multi-electron chemical bonds.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Band-selective chemical exchange saturation transfer imaging with hyperpolarized xenon-based molecular sensors.

    PubMed

    Meldrum, Tyler; Bajaj, Vikram S; Wemmer, David E; Pines, Alexander

    2011-12-01

    Molecular imaging based on saturation transfer in exchanging systems is a tool for amplified and chemically specific magnetic resonance imaging. Xenon-based molecular sensors are a promising category of molecular imaging agents in which chemical exchange of dissolved xenon between its bulk and agent-bound phases has been use to achieve sub-picomolar detection sensitivity. Control over the saturation transfer dynamics, particularly when multiple exchanging resonances are present in the spectra, requires saturation fields of limited bandwidth and is generally accomplished by continuous wave irradiation. We demonstrate instead how band-selective saturation sequences based on multiple pulse inversion elements can yield saturation bandwidth tuneable over a wide range, while depositing less RF power in the sample. We show how these sequences can be used in imaging experiments that require spatial-spectral and multispectral saturation. The results should be applicable to all CEST experiments and, in particular, will provide the spectroscopic control required for applications of arrays of xenon chemical sensors in microfluidic chemical analysis devices.

  9. Enrichment of low molecular weight serum proteins using acetonitrile precipitation for mass spectrometry based proteomic analysis.

    PubMed

    Kay, Richard; Barton, Chris; Ratcliffe, Lucy; Matharoo-Ball, Balwir; Brown, Pamela; Roberts, Jane; Teale, Phil; Creaser, Colin

    2008-10-01

    A rapid acetonitrile (ACN)-based extraction method has been developed that reproducibly depletes high abundance and high molecular weight proteins from serum prior to mass spectrometric analysis. A nanoflow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) multiple reaction monitoring (MRM) method for 57 high to medium abundance serum proteins was used to characterise the ACN-depleted fraction after tryptic digestion. Of the 57 targeted proteins 29 were detected and albumin, the most abundant protein in serum and plasma, was identified as the 20th most abundant protein in the extract. The combination of ACN depletion and one-dimensional nano-LC/MS/MS enabled the detection of the low abundance serum protein, insulin-like growth factor-I (IGF-I), which has a serum concentration in the region of 100 ng/mL. One-dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the depleted serum showed no bands corresponding to proteins of molecular mass over 75 kDa after extraction, demonstrating the efficiency of the method for the depletion of high molecular weight proteins. Total protein analysis of the ACN extracts showed that approximately 99.6% of all protein is removed from the serum. The ACN-depletion strategy offers a viable alternative to the immunochemistry-based protein-depletion techniques commonly used for removing high abundance proteins from serum prior to MS-based proteomic analyses.

  10. 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.

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

    PubMed Central

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

    2009-01-01

    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 non-fluorescent 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 (~60) exceeding the performance characteristics of many conventionally-available MB probes. PMID:19191492

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

    SciTech Connect

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

    2016-07-14

    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.

  13. Visualizing BPA by molecularly imprinted ratiometric fluorescence sensor based on dual emission nanoparticles.

    PubMed

    Lu, Hongzhi; Xu, Shoufang

    2017-06-15

    Construction of ratiometric fluorescent probe often involved in tedious multistep preparation or complicated coupling or chemical modification process. The emergence of dual emission fluorescent nanoparticles would simplify the construction process and avoids the tedious chemical coupling. Herein, we reported a facile strategy to prepare ratiometric fluorescence molecularly imprinted sensor based on dual emission nanoparticles (d-NPs) which comprised of carbon dots and gold nanoclusters for detection of Bisphenol A (BPA). D-NPs emission at 460nm and 580nm were first prepared by seed growth co-microwave method using gold nanoparticles as seeds and glucose as precursor for carbon dots. When they were applied to propose ratiometric fluorescence molecularly imprinted sensor, the preparation process was simplified, and the sensitivity of sensor was improved with detection limit of 29nM, and visualizing BPA was feasible based on the distinguish fluorescence color change. The feasibility of the developed method in real samples was successfully evaluated through the analysis of BPA in water samples with satisfactory recoveries of 95.9-98.9% and recoveries ranging from 92.6% to 98.6% in canned food samples. When detection BPA in positive feeding bottles, the results agree well with those obtained by accredited method. The developed method proposed in this work to prepare ratiometric fluorescence molecularly imprinted sensor based on dual emission nanoparticles proved to be a convenient, reliable and practical way to prepared high sensitive and selective fluorescence sensors.

  14. Thermophysical Properties of Homologous Tetracyanoborate-Based Ionic Liquids Using Experiments and Molecular Dynamics Simulations.

    PubMed

    Koller, Thomas M; Ramos, Javier; Schulz, Peter S; Economou, Ioannis G; Rausch, Michael H; Fröba, Andreas P

    2017-04-27

    Thermophysical properties of low-viscosity ionic liquids (ILs) based on the tetracyanoborate ([B(CN)4](-)) anion carrying a homologous series of 1-alkyl-3-methylimidazolium ([AMIM](+)) cations [EMIM](+) (ethyl), [BMIM](+) (butyl), [HMIM](+) (hexyl), [OMIM](+) (octyl), and [DMIM](+) (decyl) were investigated by experimental methods and molecular dynamics (MD) simulations at atmospheric pressure and various temperatures. Spectroscopic methods based on nuclear magnetic resonance and surface light scattering were applied to measure the ion self-diffusion coefficients and dynamic viscosity, respectively. In terms of MD simulations, a nonpolarizable molecular model for [EMIM][B(CN)4] developed by optimization to experimental data was transferred to the other homologous ILs. For the appropriate description of the inter- and intramolecular interactions, precise and approximate force fields (FFs) were tested regarding their transferability within the homologous IL series, aiming at reducing the computational effort in molecular simulations. It is shown that at comparable simulated and experimental densities, the calculated and measured data for viscosity and self-diffusion coefficients of the ILs agree well mostly within combined uncertainties, but deviate stronger for longer-chained ILs using an overly coarse FF model. For the [B(CN)4](-)-based ILs studied, a comparison with literature data, the influence of varying alkyl chain length in the cation on their structural and thermophysical properties, and a correlation between self-diffusivity and viscosity are discussed.

  15. Fluorescent films based on molecular-gel networks and their sensing performances.

    PubMed

    Liu, Ke; Liu, Taihong; Chen, Xiangli; Sun, Xiaohuan; Fang, Yu

    2013-10-09

    A pyrene-capped terthiophene of cholesteryl derivative (CholG-3T-Py) was designed, synthesized, and utilized for the fabrication of a fluorescent film. Unlike the commonly adopted direct-coating method, the film was fabricated by the physical immobilization of the fluorophore, CholG-3T-Py, onto a glass plate surface via preformed low-molecular-mass gelator (LMMGs)-based molecular-gel networks. The photophysical behavior of the film as prepared and its sensing performances to nitrobenzene (NB) were conducted after activation with toluene. It was found that the film as prepared and activated is sensitive to the presence of NB, and the sensing process is fully reversible. Furthermore, the effects of commonly found interferents, including structural analogues, raw materials, which are commonly used for the production of NB, and other nitroaromatics (NACs), on the sensing process were also tested. It was shown that only aniline and phenol possess slight interference. The present work not only extends the applications of LMMGs-based molecular gels but also provids a new approach for preparation of micro- and nano-structure-based fluorescent sensing films.

  16. Band-selective chemical exchange saturation transfer imaging with hyperpolarized xenon-based molecular sensors

    NASA Astrophysics Data System (ADS)

    Meldrum, Tyler; Bajaj, Vikram S.; Wemmer, David E.; Pines, Alexander

    2011-12-01

    Molecular imaging based on saturation transfer in exchanging systems is a tool for amplified and chemically specific magnetic resonance imaging. Xenon-based molecular sensors are a promising category of molecular imaging agents in which chemical exchange of dissolved xenon between its bulk and agent-bound phases has been use to achieve sub-picomolar detection sensitivity. Control over the saturation transfer dynamics, particularly when multiple exchanging resonances are present in the spectra, requires saturation fields of limited bandwidth and is generally accomplished by continuous wave irradiation. We demonstrate instead how band-selective saturation sequences based on multiple pulse inversion elements can yield saturation bandwidth tuneable over a wide range, while depositing less RF power in the sample. We show how these sequences can be used in imaging experiments that require spatial-spectral and multispectral saturation. The results should be applicable to all CEST experiments and, in particular, will provide the spectroscopic control required for applications of arrays of xenon chemical sensors in microfluidic chemical analysis devices.

  17. Computational prediction and experimental selectivity coefficients for hydroxyzine and cetirizine molecularly imprinted polymer based potentiometric sensors.

    PubMed

    Azimi, Abolfazl; Javanbakht, Mehran

    2014-02-17

    In spite of the increasing usages number of molecularly imprinted polymers (MIPs) in many scientific applications, the theoretical aspects of participating intra molecular forces are not fully understood. This work investigates effects of the electrostatic force, the Mulliken charge and the role of cavity's backbone atoms on the selectivity of MIPs. Moreover, charge distribution, which is a computational parameter, was proposed for the prediction of the selectivity coefficients of MIP-based sensors. In the computational approaches and experimental study, methacrylic acid (MAA) was chosen as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross linker for hydroxyzine and cetirizine imprinted polymers. Ab initio, DFT B3LYP method was carried out on molecular optimization. With regard to results obtained from molecules optimization and hydrogen bonding properties, possible configurations of 1:n (n≤5) template/monomer complexes were designed and optimized. The binding energy for each complex in gas phase was calculated. Depending on the most stable configuration, hydroxyzine and cetirizine imprinted polymer models were designed. The calculations including the porogen were also investigated. The theoretical charge distributions for the template and some potential interfering molecules were calculated. The results showed a correlation between the selectivity coefficients and the theoretical charge distributions. The results surprisingly show that charge distribution based model was able to predict the selectivity coefficients of MIP based potentiometric sensors.

  18. Magnetoresistance of nanoscale molecular devices based on Aharonov-Bohm interferometry.

    PubMed

    Hod, Oded; Baer, Roi; Rabani, Eran

    2008-09-24

    Control of conductance in molecular junctions is of key importance in the growing field of molecular electronics. The current in these junctions is often controlled by an electric gate designed to shift conductance peaks into the low bias regime. Magnetic fields, on the other hand, have rarely been used due to the small magnetic flux captured by molecular conductors (an exception is the Kondo effect in single-molecule transistors). This is in contrast to a related field, electronic transport through mesoscopic devices, where considerable activity with magnetic fields has led to a rich description of transport. The scarcity of experimental activity is due to the belief that significant magnetic response is obtained only when the magnetic flux is of the order of the quantum flux, while attaining such a flux for molecular and nanoscale devices requires unrealistic magnetic fields. Here we review recent theoretical work regarding the essential physical requirements necessary for the construction of nanometer-scale magnetoresistance devices based on an Aharonov-Bohm molecular interferometer. We show that control of the conductance properties using small fractions of a magnetic flux can be achieved by carefully adjusting the lifetime of the conducting electrons through a pre-selected single state that is well separated from other states due to quantum confinement effects. Using a simple analytical model and more elaborate atomistic calculations we demonstrate that magnetic fields which give rise to a magnetic flux comparable to 10(-3) of the quantum flux can be used to switch a class of different molecular and nanometer rings, ranging from quantum corrals, carbon nanotubes and even a molecular ring composed of polyconjugated aromatic materials. The unique characteristics of the magnetic field as a gate is further discussed and demonstrated in two different directions. First, a three-terminal molecular router devices that can function as a parallel logic gate, processing

  19. TOPICAL REVIEW: Magnetoresistance of nanoscale molecular devices based on Aharonov Bohm interferometry

    NASA Astrophysics Data System (ADS)

    Hod, Oded; Baer, Roi; Rabani, Eran

    2008-09-01

    Control of conductance in molecular junctions is of key importance in the growing field of molecular electronics. The current in these junctions is often controlled by an electric gate designed to shift conductance peaks into the low bias regime. Magnetic fields, on the other hand, have rarely been used due to the small magnetic flux captured by molecular conductors (an exception is the Kondo effect in single-molecule transistors). This is in contrast to a related field, electronic transport through mesoscopic devices, where considerable activity with magnetic fields has led to a rich description of transport. The scarcity of experimental activity is due to the belief that significant magnetic response is obtained only when the magnetic flux is of the order of the quantum flux, while attaining such a flux for molecular and nanoscale devices requires unrealistic magnetic fields. Here we review recent theoretical work regarding the essential physical requirements necessary for the construction of nanometer-scale magnetoresistance devices based on an Aharonov-Bohm molecular interferometer. We show that control of the conductance properties using small fractions of a magnetic flux can be achieved by carefully adjusting the lifetime of the conducting electrons through a pre-selected single state that is well separated from other states due to quantum confinement effects. Using a simple analytical model and more elaborate atomistic calculations we demonstrate that magnetic fields which give rise to a magnetic flux comparable to 10-3 of the quantum flux can be used to switch a class of different molecular and nanometer rings, ranging from quantum corrals, carbon nanotubes and even a molecular ring composed of polyconjugated aromatic materials. The unique characteristics of the magnetic field as a gate is further discussed and demonstrated in two different directions. First, a three-terminal molecular router devices that can function as a parallel logic gate, processing

  20. 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

  1. A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent.

    PubMed

    Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2010-03-01

    Multi-modal molecular imaging can significantly improve the potential of non-invasive medical diagnosis by combining basic anatomical descriptions with in-depth phenotypic characteristics of disease. Contrast agents with multifunctional properties that can sense and enhance the signature of specific molecular markers, together with high biocompatibility are essential for combinatorial molecular imaging approaches. Here, we report a multi-modal contrast agent based on hydroxyapatite nanocrystals (nHAp), which is engineered to show simultaneous contrast enhancement for three major molecular imaging techniques such as magnetic resonance imaging (MRI), X-ray imaging and near-infrared (NIR) fluorescence imaging. Monodispersed nHAp crystals of average size approximately 30 nm and hexagonal crystal structure were in situ doped with multiple rare-earth impurities by a surfactant-free, aqueous wet-chemical method at 100 degrees C. Doping of nHAp with Eu(3+) (3 at%) resulted bright near-infrared fluorescence (700 nm) due to efficient (5)D(0)-(7)F(4) electronic transition and co-doping with Gd(3+) resulted enhanced paramagnetic longitudinal relaxivity (r(1) approximately 12 mM(-1) s(-1)) suitable for T(1) weighted MR imaging together with approximately 80% X-ray attenuation suitable for X-ray contrast imaging. Capability of MF-nHAp to specifically target and enhance the signature of molecular receptors (folate) in cancer cells was realized by carbodiimide grafting of cell-membrane receptor ligand folic acid (FA) on MF-nHAp surface aminized with dendrigraft polymer, polyethyleneimine (PEI). The FA-PEI-MF-nHAp conjugates showed specific aggregation on FR(+ve) cells while leaving the negative control cells untouched. Nanotoxicity evaluation of this multifunctional nHAp carried out on primary human endothelial cells (HUVEC), normal mouse lung fibroblast cell line (L929), human nasopharyngeal carcinoma (KB) and human lung cancer cell line (A549) revealed no apparent toxicity even

  2. 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(®).

  3. 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.

  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. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Logic integration of mRNA signals by an RNAi-based molecular computer.

    PubMed

    Xie, Zhen; Liu, Siyuan John; Bleris, Leonidas; Benenson, Yaakov

    2010-05-01

    Synthetic in vivo molecular 'computers' could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that 'transduce' mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi 'computational' module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting.

  6. Genetic variability among elite popcorn lines based on molecular and morphoagronomic characteristics.

    PubMed

    Dos Santos, J F; Mangolin, C A; Machado, M F P S; Scapim, C A; Giordani, W; Gonçalves, L S A

    2017-06-29

    Knowledge of genetic diversity among genotypes and relationships among elite lines is of great importance for the development of breeding programs. Therefore, the objective of this study was to evaluate genetic variability based on the morphoagronomic and molecular characterization of 18 elite popcorn (Zea mays var. everta) lines to be used by Universidade Estadual de Maringá breeding programs. We used 31 microsatellite primers (widely distributed in the genome), and 16 morphological descriptors (including the resistance to maize white spot, common rust, polysora rust of maize, cercospora and leaf blights). The molecular data revealed variability among the lines, which were divided into four groups that were partially concordant with unweighted pair group method with arithmetic mean (UPMGA) and Bayesian clusters. The lines G3, G4, G11, and G13 exhibited favorable morphological characters and low disease incidence rates. The four groups were confirmed using the Gower distance in the UPGMA cluster; however, there was no association with the dissimilarity patterns obtained using the molecular data. The absence of a correlation suggests that both characterizations (morphoagronomic and molecular) are important for discriminating among elite popcorn lines.

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

    PubMed Central

    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. Molecular dynamics study of the structure and performance of simple and double bases propellants.

    PubMed

    Ma, Xiufang; Zhu, Weihua; Xiao, Jijun; Xiao, Heming

    2008-08-15

    To investigate the structure and performance of simple and double bases propellants, the nitrocellulose (NC), nitroglycerin (NG), and double mixed system (NC+NG) have been simulated by using the molecular dynamics (MD) method with the COMPASS force field. The interactions between NC and NG have been analyzed by means of pair correlation functions. The mechanical properties of the three model systems, i.e. elastic coefficients, modulus, Cauchy pressure, and Poisson's ratio, etc., have been obtained. It is found that the rigidity, ductibility, and tenacity of the double bases propellants (NC+NG) are stronger than those of simple base propellants (NC), which attributes to the effect of NG and the strong interactions between NC and NG. The detonation properties of the three systems have also been calculated and the results show that compared with the simple base propellant (NC), the detonation heat and detonation velocity of the double base propellants (NC+NG) are increased.

  9. Novel nanodispersed coal liquefaction catalysts: Molecular design via microemulsion-based synthesis

    SciTech Connect

    Osseo-Asare, K.; Radovic, L.R.

    1991-07-01

    The objective of this project is to pursue the development of highly dispersed and inexpensive catalysts for improved coal solubilization and upgrading of coal liquids. A novel study of the synthesis of liquefaction catalysts of nanometer size will be carried out. It is based on the molecular design of reverse micelles (microemulsions). These surfactant-stabilized, metal-bearing microdrops offer unique opportunities for synthesizing very small particles by providing a cage-like effect that limits particle nucleation, growth and agglomeration. The emphasis will be on iron- and molybdenum-based catalysts, but the techniques to be developed should also be generally applicable. (VC)

  10. Novel nanodispersed coal liquefaction catalysts: Molecular design via microemulsion-based synthesis

    SciTech Connect

    Osseo-Asare, K.; Radovic, L.R.

    1991-02-01

    The objective of this project is to pursue the development of highly dispersed and inexpensive catalysts for improved coal solubilization and upgrading of coal liquids. A novel study of the synthesis of liquefaction catalysts of nanometer size will be carried out. It is based on the molecular design of reverse micelles (microemulsions). These surfactant-stabilized, metal-bearing microdrops offer unique opportunities for synthesizing very small particles by providing a cage-like effects that limits particle nucleation, growth and agglomeration. The emphasis will be on iron- and molybdenum-based catalysts, but the techniques to be developed should also be generally applicable.

  11. Novel nanodispersed coal liquefaction catalysts: Molecular design via microemulsion-based synthesis

    SciTech Connect

    Osseo-Asare, K.; Boakye, E.; Vaidyanathan, N.; Radovic, L.R.

    1992-04-01

    The objective of this project is to pursue the development of highly dispersed and inexpensive catalysts for improved coal solubilization and upgrading of coal liquids. A novel study of the synthesis of liquefaction catalysts of nanometer size will be carried out. It is based on the molecular design of reverse micelles (microemulsions). These surfactant-stabilized, metal-bearing microdrops offer unique opportunities for synthesizing very small particles by providing a cage-like effect that limits particle nucleation, growth and agglomeration. The emphasis will be on iron- and molybdenum-based catalysts, but the techniques to be developed should also be generally applicable. (VC)

  12. Promising ZnO-based DSSC performance using HMP molecular dyes of high extinction coefficients.

    PubMed

    Ganesh, T; Nguyen, Hong-Minh; Mane, Rajaram S; Kim, Nakjoong; Shinde, Dipak V; Bhande, Sambhaji S; Naushad, Mu; Hui, K N; Han, Sung Hwan

    2014-08-07

    Employing newly synthesized di-substituted tri-phenyl amine (HMP-9) and carbazole (HMP-11) dyes (with limited acidic carboxyl anchor groups), a power conversion efficiency as high as 7.03% in ZnO nanocrystallite (NC)-based dye-sensitized solar cells (DSSCs) is achieved. The specific molecular designs of HMP-09 and HMP-11 consisting of with and without hexyloxy spacer groups, and added tri-phenyl amine or 9-phenyl-9H-carbazole donor groups, respectively, attached on the ancillary ligands are advantageous, evidenced from electrochemical impedance spectroscopy measurements, for ZnO NC-based DSSCs.

  13. Multilayer Growth of Porphyrin-Based Polyurea Thin Film Using Solution-Based Molecular Layer Deposition Technique.

    PubMed

    Uddin, S M Nizam; Nagao, Yuki

    2017-10-12

    Controllable synthesis of organic thin film materials on solid surfaces is a challenging issue in the research field of surface science as it is affected by several physical parameters. In this work, we demonstrated a solution-based molecular layer deposition (MLD) approach to prepare porphyrin-based covalent organic molecular networks on a 3-aminopropyl trimethoxysilane (APTMS) modified substrate surface using the urea coupling reaction between 1,4-phenylene diisocyanate (1,4-PDI) and 5,10,15,20-tetrakis-(4-aminophenyl) porphyrin (H2TAPP) at room temperature (22 ± 2 ºC). Multilayer growth was investigated under different relative humidity (RH) conditions of the reaction chamber. Sequential molecular growth at low relative humidity (≤10% RH) was observed using UV-vis absorption spectroscopy and atomic force microscopy (AFM). The high-RH condition shows limited film growth. Infrared spectroscopy (IR) and X-ray photoelectron spectroscopy (XPS) revealed the polyurea bond formation in sequential multilayer thin films, demonstrating that stepwise multilayer film growth was achieved using the urea coupling reaction.

  14. Multiplatform-based molecular subtypes of non-small-cell lung cancer.

    PubMed

    Chen, F; Zhang, Y; Parra, E; Rodriguez, J; Behrens, C; Akbani, R; Lu, Y; Kurie, J M; Gibbons, D L; Mills, G B; Wistuba, I I; Creighton, C J

    2017-03-01

    Non-small-cell lung cancer (NSCLC) demonstrates remarkable molecular diversity. With the completion of The Cancer Genome Atlas (TCGA), there is opportunity for systematic analyses of the entire TCGA NSCLC cohort, including comparisons and contrasts between different disease subsets. On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy, and RNA and protein expression), 1023 NSCLC cases-519 from TCGA adenocarcinoma (AD) project and 504 from TCGA squamous cell carcinoma (SQCC) project-were classified using a 'cluster-of-clusters' analytic approach. Patterns from TCGA NSCLC subsets were examined in independent external databases, including the PROSPECT (Profiling of Resistance patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax) NSCLC data set. Nine genomic subtypes of NSCLC were identified, three within SQCC and six within AD. SQCC subtypes were associated with transcriptional targets of SOX2 or p63. One predominately AD subtype (with a large proportion of SQCC) shared molecular features with neuroendocrine tumors. Two AD subtypes manifested a CpG island methylator phenotype. Three AD subtypes showed high p38 and mTOR pathway activation. AD subtypes associated with low differentiation showed relatively worse prognosis. SQCC subtypes and two of the AD subtypes expressed cancer testis antigen genes, whereas three AD subtypes expressed several immune checkpoint genes including PDL1 and PDL2, corresponding with patterns of greater immune cell infiltration. Subtype associations for several immune-related markers-including PD1, PDL1, CD3 and CD8-were confirmed in the PROSPECT cohort using immunohistochemistry. NSCLC molecular subtypes have therapeutic implications and lend support to a personalized approach to NSCLC management based on molecular characterization.

  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. A Bayesian Target Predictor Method based on Molecular Pairing Energies estimation

    PubMed Central

    Oliver, Antoni; Canals, Vincent; Rosselló, Josep L.

    2017-01-01

    Virtual screening (VS) is applied in the early drug discovery phases for the quick inspection of huge molecular databases to identify those compounds that most likely bind to a given drug target. In this context, there is the necessity of the use of compact molecular models for database screening and precise target prediction in reasonable times. In this work we present a new compact energy-based model that is tested for its application to Virtual Screening and target prediction. The model can be used to quickly identify active compounds in huge databases based on the estimation of the molecule’s pairing energies. The greatest molecular polar regions along with its geometrical distribution are considered by using a short set of smart energy vectors. The model is tested using similarity searches within the Directory of Useful Decoys (DUD) database. The results obtained are considerably better than previously published models. As a Target prediction methodology we propose the use of a Bayesian Classifier that uses a combination of different active compounds to build an energy-dependent probability distribution function for each target. PMID:28263323

  17. Potential of molecular based diagnostics and its impact on allergen immunotherapy.

    PubMed

    Melioli, Giovanni; Savi, Eleonora; Crivellaro, Maria Angiola; Passalacqua, Giovanni

    2016-01-01

    Molecular based in vitro technologies greatly changed the diagnostic approaches in allergy. At present, sensitization profiles can be dissected according to IgE subsets, which are specific for genuine or cross-reacting components and potentially dangerous or virtually harmless components. The identification of IgE in components with specific characteristics has a direct impact on the accuracy of the diagnosis (indeed, it is possible at present to not only identify the allergen derived from a given allergen source but also the family of molecules to which the patient is sensitized), on the prognosis of the patient's allergy, and on the prevention activities to be implemented. More interestingly, during the last few years, and thanks to the tools of molecular diagnostics, the indications for Allergen Immunotherapy (AIT) have also be modified, and novel strategies for the selection of the allergens to be administered have been better defined. Indeed, protocols indicating how Molecular Based Diagnosis (MBD) can be used to identify the best AIT approach have been recently published. In this review, the rationale for the use of MBD tools is discussed, and the recent strategies for the choice of allergens to be used in AIT are reported.

  18. A Bayesian Target Predictor Method based on Molecular Pairing Energies estimation

    NASA Astrophysics Data System (ADS)

    Oliver, Antoni; Canals, Vincent; Rosselló, Josep L.

    2017-03-01

    Virtual screening (VS) is applied in the early drug discovery phases for the quick inspection of huge molecular databases to identify those compounds that most likely bind to a given drug target. In this context, there is the necessity of the use of compact molecular models for database screening and precise target prediction in reasonable times. In this work we present a new compact energy-based model that is tested for its application to Virtual Screening and target prediction. The model can be used to quickly identify active compounds in huge databases based on the estimation of the molecule’s pairing energies. The greatest molecular polar regions along with its geometrical distribution are considered by using a short set of smart energy vectors. The model is tested using similarity searches within the Directory of Useful Decoys (DUD) database. The results obtained are considerably better than previously published models. As a Target prediction methodology we propose the use of a Bayesian Classifier that uses a combination of different active compounds to build an energy-dependent probability distribution function for each target.

  19. 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

  20. Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Shan, Liang; Chopra, Arvind; Leung, Kam; Eckelman, William C.; Menkens, Anne E.

    2012-09-01

    The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, 4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

  1. A Bayesian Target Predictor Method based on Molecular Pairing Energies estimation.

    PubMed

    Oliver, Antoni; Canals, Vincent; Rosselló, Josep L

    2017-03-06

    Virtual screening (VS) is applied in the early drug discovery phases for the quick inspection of huge molecular databases to identify those compounds that most likely bind to a given drug target. In this context, there is the necessity of the use of compact molecular models for database screening and precise target prediction in reasonable times. In this work we present a new compact energy-based model that is tested for its application to Virtual Screening and target prediction. The model can be used to quickly identify active compounds in huge databases based on the estimation of the molecule's pairing energies. The greatest molecular polar regions along with its geometrical distribution are considered by using a short set of smart energy vectors. The model is tested using similarity searches within the Directory of Useful Decoys (DUD) database. The results obtained are considerably better than previously published models. As a Target prediction methodology we propose the use of a Bayesian Classifier that uses a combination of different active compounds to build an energy-dependent probability distribution function for each target.

  2. Tunable electronic structures and optical properties of fluorenone-based molecular materials by heteroatoms.

    PubMed

    Song, Peng; Ma, Fengcai

    2010-02-11

    The ground-state and excited-state electronic structures as well as the tunable optical properties of a variety of newly designed fluorenone-based molecular materials have been theoretically investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. The substitutes on the O atom in the carbonyl group of the fluorenone (FN) molecule with S (FN-C=S), Se (FN-C=Se), and Te (FN-C=Te) atoms can significantly influence their electronic structures, molecular orbitals, geometric conformations, and optical properties of fluorenone-based molecular materials. Due to the important difference of electronegativity for O, S, Se, and Te atoms in the same group, the ground-state dipole moment of these fluorenone-based molecular materials is gradually decreased in the order FN, FN-C=S, FN-C=Se, and FN-C=Te. At the same time, the ground-state bond length of the C=X (X refers O, S, Se, and Te) is gradually increased in the order of FN, FN-C=S, FN-C=Se, and FN-C=Te. Due to the different nature of the S(1) state for FN (pipi* character) and FN-C=S, FN-C=Se, and FN-C=Te (sigmapi* character), the excited-state dipole moment of FN in the S(1) state is dramatically increased in comparison with that in the ground state; however, the excited-state dipole moments of FN-C=S, FN-C=Se, and FN-C=Te are significantly diminished. In addition, the excited-state bond length of C=X (X refers O, S, Se, and Te) in the S(1) state is lengthened in comparison with that in the ground state due to the photoexcitation of the C=X bond FN, FN-C=S, FN-C=Se, and FN-C=Te. On the other hand, the energy level of the HOMO orbital is heightened and that of LUMO orbital is lowered with the introduction of heteroatoms in the order of S, Se, and Te. Consequently, the energy gap between LUMO and HOMO orbtials is gradually decreased in the order of the FN, FN-C=S, FN-C=Se, and FN-C=Te. Consequently, the calculated fluorescence wavelengths are strongly red-shifted from the

  3. Considerations on the Design of a Molecular Frequency Standard Based on the Molecular Beam Electric Resonance Method

    NASA Technical Reports Server (NTRS)

    Hughes, Vernon W.

    1959-01-01

    The use of a rotational state transition as observed by the molecular beam electric resonance method is discussed as a possible frequency standard particularly in the millimeter wavelength range. As a promising example the 100 kMc transition between the J = 0 and J = 1 rotational states of Li 6F19 is considered. The relative insensitivity of the transition frequency to external electric and magnetic fields and the low microwave power requirements appear favorable; the small fraction of the molecular beam that is in a single rotational state is a limiting factor.

  4. A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: advantages of pathway-based discovery.

    PubMed

    Hellerstein, Marc K

    2008-01-01

    Contemporary drug discovery and development (DDD) is dominated by a molecular target-based paradigm. Molecular targets that are potentially important in disease are physically characterized; chemical entities that interact with these targets are identified by ex vivo high-throughput screening assays, and optimized lead compounds enter testing as drugs. Contrary to highly publicized claims, the ascendance of this approach has in fact resulted in the lowest rate of new drug approvals in a generation. The primary explanation for low rates of new drugs is attrition, or the failure of candidates identified by molecular target-based methods to advance successfully through the DDD process. In this essay, I advance the thesis that this failure was predictable, based on modern principles of metabolic control that have emerged and been applied most forcefully in the field of metabolic engineering. These principles, such as the robustness of flux distributions, address connectivity relationships in complex metabolic networks and make it unlikely a priori that modulating most molecular targets will have predictable, beneficial functional outcomes. These same principles also suggest, however, that unexpected therapeutic actions will be common for agents that have any effect (i.e., that complexity can be exploited therapeutically). A potential operational solution (pathway-based DDD), based on observability rather than predictability, is described, focusing on emergent properties of key metabolic pathways in vivo. Recent examples of pathway-based DDD are described. In summary, the molecular target-based DDD paradigm is built on a naïve and misleading model of biologic control and is not heuristically adequate for advancing the mission of modern therapeutics. New approaches that take account of and are built on principles described by metabolic engineers are needed for the next generation of DDD.

  5. 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.

  6. Molecular determinants for cyclo-oligosaccharide-based nanoparticle-mediated effective siRNA transfection.

    PubMed

    Manzanares, Darío; Araya-Durán, Ingrid; Gallego-Yerga, Laura; Játiva, Pablo; Márquez-Miranda, Valeria; Canan, Jonathan; Jiménez Blanco, José Luis; Mellet, Carmen Ortiz; González-Nilo, Fernando Danilo; García Fernández, José Manuel; Ceña, Valentín

    2017-07-01

    To study the structural requirements that a cyclooligosaccharide-based nanoparticle must fulfill to be an efficient siRNA transfection vector. siRNA protection from degradation by RNAses, transfection efficiency and the thermodynamic parameters of the nanoparticle/siRNA interactions were studied on pairs of amphiphilic molecules using biochemical techniques and molecular dynamics. The lower the siRNA solvent accessible surface area in the presence of the nanoparticle, higher the protection from RNAse-mediated degradation in the corresponding nanocomplex; a moderate nanoparticle/siRNA binding energy value further facilitates reversible complexation and binding to the target cellular mRNA. The use, in advance, of these parameters will provide a useful indication of the potential of a molecular nanoparticle as siRNA transfecting vector.

  7. Gold nanoprobe-based non-crosslinking hybridization for molecular diagnostics.

    PubMed

    Larguinho, Miguel; Canto, Rafaela; Cordeiro, Milton; Pedrosa, Pedro; Fortuna, Andreia; Vinhas, Raquel; Baptista, Pedro V

    2015-01-01

    Non-crosslinking (NCL) approaches using DNA-modified gold nanoparticles for molecular detection constitute powerful tools with potential implications in clinical diagnostics and tailored medicine. From detection of pathogenic agents to identification of specific point mutations associated with health conditions, these methods have shown remarkable versatility and simplicity. Herein, the NCL hybridization assay is broken down to the fundamentals behind its assembly and detection principle. Gold nanoparticle synthesis and derivatization is addressed, emphasizing optimal size homogeneity and conditions for maximum surface coverage, with direct implications in downstream detection. The detection principle is discussed and the advantages and drawbacks of different NCL approaches are discussed. Finally, NCL-based applications for molecular detection of clinically relevant loci and potential integration into more complex biosensing platforms, projecting miniaturization and portability are addressed.

  8. 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.

  9. Discrimination of Neotropical Anopheles species based on molecular and wing geometric morphometric traits.

    PubMed

    Gómez, Giovan F; Correa, Margarita M

    2017-10-01

    Morphological similarities among closely related Anopheles species that differ in biological traits and malaria transmission represent a challenge in medical entomology; therefore, new tools are constantly tested to bring solutions. Particularly, in this work, a geometric morphometric analysis of wing geometry variation, based on morphologically and molecularly identified specimens, was applied for the discrimination of fourteen Anopheles species belonging to the Nyssorhynchus, Anopheles and Kerteszia subgenera. DNA barcodes helped to confirm species assignation and the geometric morphometric approach revealed wing form differences not only at the subgenera but also at the species level. Each subgenus presented a particular wing size trend, possibly related to the evolutionary history of these lineages. Wing shape allowed species discrimination, except for some very closely related taxa. The current findings highlight the importance of using complementary approaches involving morphological and molecular data for Anopheles species discrimination. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Discriminating single-molecule sensing by crown-ether-based molecular junctions

    NASA Astrophysics Data System (ADS)

    Ismael, Ali K.; Al-Jobory, Alaa; Grace, Iain; Lambert, Colin J.

    2017-02-01

    Crown-ether molecules are well known to selectively bind alkali atoms, so by incorporating these within wires, any change in electrical conductance of the wire upon binding leads to discriminating sensing. Using a density functional theory-based approach to quantum transport, we investigate the potential sensing capabilities of single-molecule junctions formed from crown ethers attached to anthraquinone units, which are in turn attached to gold electrodes via alkyl chains. We calculate the change in electrical conductance for binding of three different alkali ions (lithium, sodium, and potassium). Depending on the nature of the ionic analyte, the conductance is enhanced by different amounts. This change in electrical conductance is due to charge transfer from the ion to molecular wire causing the molecular resonances to shift closer to the electrode Fermi energy.

  11. 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).

  12. 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.

  13. High-Resolution Mesoscopic Fluorescence Molecular Tomography Based on Compressive Sensing

    PubMed Central

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

    2017-01-01

    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. PMID:25137718

  14. 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

  15. The identification of molecular surfaces' feature regions based on spherical mapping

    NASA Astrophysics Data System (ADS)

    Zhang, Meiling; Zhang, Jingqiao

    2017-02-01

    As possible active sites, the concave and convex feature regions of the molecule are the locations where the molecular docking will happen more possibly. Then how to search for those regions is valuable to study. In this paper, a new method is proposed for identifying concave and convex regions. Based on the established spherical mapping between molecular surfaces and its bounding-sphere surfaces, the concave and convex vertices of local areas can be determined according to the expansion distance defined by the spherical mapping. Then through mesh growing, a feature region can be firmed by a concave point or a convex point, also called center point, and its neighboring faces, whose normal vector has an angle in a specified range with the center point. After that, areas and volumes of feature regions are calculated. The experimental results indicate that the method can well identify the concave and convex characteristics of the molecule.

  16. Controlled Sol-Gel Transitions by Actuating Molecular Machine Based Supramolecular Polymers.

    PubMed

    Goujon, Antoine; Mariani, Giacomo; Lang, Thomas; Moulin, Emilie; Rawiso, Michel; Buhler, Eric; Giuseppone, Nicolas

    2017-04-05

    The implementation of artificial molecular machines in polymer science is an important objective that challenges chemists and physicists in order to access an entirely new class of smart materials. To design such systems, the amplification of a mechanical actuation from the nanoscale up to a macroscopic response in the bulk material is a central issue. In this article we show that bistable [c2]daisy chain rotaxanes (i.e., molecular muscles) can be linked into main-chain Upy-based supramolecular polymers. We then reveal by an in depth quantitative study that the pH actuation of the mechanically active rotaxane at the nanoscale influences the physical reticulation of the polymer chains by changing the supramolecular behavior of the Upy units. This nanoactuation within the local structure of the main chain polymer results in a mechanically controlled sol-gel transition at the macroscopic level.

  17. 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. (c) 2004 American Institute of Physics.

  18. 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).

  19. A molecularly imprinted sensor based on an electrochemiluminescent membrane for ultratrace doxycycline determination.

    PubMed

    Li, Shuhuai; Li, Jianping; Lin, Qingyu; Wei, Xiaoping

    2015-07-07

    A new molecularly imprinted sensor was developed based on an electroluminescent molecularly imprinted polymer (MIP) membrane and used for doxycycline determination. The MIP was prepared by electropolymerization of pyrogallol doped with alizarin red. An electrochemiluminescence (ECL) signal was produced by the oxidation of the poly-pyrogallol polymer and reaction with alizarin red. The luminescence intensity was enhanced by doxycycline molecules which were re-adsorbed in cavities in MIP due to the energy transfer of the doxycycline oxidized intermediate to alizarin red. The changes of ECL intensities were linear with the concentrations of doxycycline in the range of 2 × 10(-10) to 5 × 10(-8) mol L(-1). The detection limit was 5.17 × 10(-11) mol L(-1). This method was utilized to determine doxycycline residuals in fish muscles with satisfactory results.

  20. 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.

  1. 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

  2. A phylogeny of the family Poritidae (Cnidaria, Scleractinia) based on molecular and morphological analyses.

    PubMed

    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.

  3. 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.

  4. 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.

  5. 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

    2016-07-05

    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.

  6. Structural and molecular docking studies of biologically active mercaptopyrimidine Schiff bases

    NASA Astrophysics Data System (ADS)

    Kirubavathy, S. Jone; Velmurugan, R.; Karvembu, R.; Bhuvanesh, N. S. P.; Enoch, Israel V. M. V.; Selvakumar, P. Mosae; Premnath, D.; Chitra, S.

    2017-01-01

    Novel Schiff bases derived from the treatment of mercapto-diamino pyrimidine with two different aldehydes are characterized using elemental analysis, single crystal X-ray diffraction and 1H NMR spectroscopy. The pharmacological action of the synthesized compounds viz., antimicrobial, anticancer and antitubercular activities is studied. The Schiff bases show a very good activity against various test pathogens. DNA and β-CD binding interactions of the compounds are studied using UV-Visible absorption and fluorescence spectral measurements. The binding constants of the compounds towards β-CD are in the order of 103 to 104. Molecular docking is done using MOE program on the 3D structure of the enzymes, viz., human thymidylate synthase complexed with dump and raltitrex, candida albicans N-myristoyltransferasepeptidic inhibitor, catalytic domain of protein kinase pKnb from mycobacterium tuberculosis in complex with mitoxantrone, pare, topoisomerase atpase inhibitor, E. coli and lactobacillus casdihydrofolatereductase. The MIC/IC50 values of the Schiff bases are compared with the glide scores from the molecular docking studies. The number of hydrogen bonding interactions between the Schiff bases and amino acid residues are also reported.

  7. 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.

  8. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. SalmoBase: an integrated molecular data resource for Salmonid species.

    PubMed

    Samy, Jeevan Karloss Antony; Mulugeta, Teshome Dagne; Nome, Torfinn; Sandve, Simen Rød; Grammes, Fabian; Kent, Matthew Peter; Lien, Sigbjørn; Våge, Dag Inge

    2017-06-26

    Salmonids are ray-finned fishes which constitute 11 genera and at least 70 species including Atlantic salmon, whitefishes, graylings, rainbow trout, and char. The common ancestor of all Salmonidae experienced a whole genome duplication (WGD) ~80 million years ago, resulting in an autotetraploid genome. Genomic rediplodization is still going on in salmonid species, providing an unique system for studying evolutionary consequences of whole genome duplication. In recent years, high quality genome sequences of Atlantic salmon and Rainbow trout has been established, due to their scientific and commercial values. In this paper we introduce SalmoBase ( http://www.salmobase.org/ ), a tool for making molecular resources for salmonids public available in a framework of visualizations and analytic tools. SalmoBase has been developed as a part of the ELIXIR.NO project. Currently, SalmoBase contains molecular resources for Atlantic salmon and Rainbow trout. Data can be accessed through BLAST, Genome Browser (GBrowse), Genetic Variation Browser (GVBrowse) and Gene Expression Browser (GEBrowse). To the best of our knowledge, SalmoBase is the first database which integrates salmonids data and allow users to study salmonids in an integrated framework. The database and its tools (e.g., comparative genomics tools, synteny browsers) will be expanded as additional public resources describing other Salmonidae genomes become available.

  10. Genetic diversity of the pneumococcal capsule: implications for molecular-based serotyping.

    PubMed

    McEllistrem, Mary Catherine

    2009-09-01

    Streptococcus pneumoniae remains an important pathogen despite licensure of a seven-valent pneumococcal protein conjugate vaccine. As a result, serotyping strains remains of paramount importance to both assess the effectiveness of current vaccines and closely monitor for the emergence of nonvaccine strains. Given the limitations of the quellung reaction, both molecular and immunology-based serotyping methods have been pursued. Currently, the most promising assay combines an immunologic assay with multiplex PCR of serotype-specific genes. The key limitation with a molecular-based assay is the plasticity of the pneumococcus, as capsular transformation or point mutations could easily result in serotype misclassification. Based on the currently available techniques, a comprehensive immunology-based assay appears to be the most promising alternative to the quellung reaction. In the future, assays that utilize high-throughput sequencing technology and/or matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) could lead to a novel pneumococcal serotyping method.

  11. 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

  12. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Friction in carborane-based molecular rotors driven by gas flow or electric field: classical molecular dynamics.

    PubMed

    Prokop, Alexandr; Vacek, Jaroslav; Michl, Josef

    2012-03-27

    Friction in molecular rotors is examined by classical molecular dynamics simulations for grid-mounted azimuthal dipolar molecular rotors, whose rotation is either allowed to decay freely or is driven at GHz frequencies by a flow of rare gas or by a rotating electric field. The rotating parts (rotators) are propeller-shaped. Their two to six blades consist of condensed aromatic rings and are attached to a deltahedral carborane hub, whose antipodal carbons carry [n]staffane axles mounted on a square molecular grid. The dynamic friction constant η has been derived in several independent ways with similar results. Analysis of free rotation decay yields η as a continuous exponentially decreasing function of rotor frequency. The calculated dependence of friction torque on frequency resembles the classical macroscopic Stribeck curve. Its relation to rotational potential energy barriers and the key role of the rate of intramolecular vibrational redistribution (IVR) of energy and angular momentum from rotator rotation to other modes are considered in two limiting regimes. (i) In the strongly overdamped regime, rotation is much slower than IVR, and effective friction can be expressed through potential barriers to rotation. (ii) In the strongly underdamped regime, rotation is much faster than IVR, whose rate then determines friction.

  14. AN EFFICIENT HIGHER-ORDER FAST MULTIPOLE BOUNDARY ELEMENT SOLUTION FOR POISSON-BOLTZMANN BASED MOLECULAR ELECTROSTATICS

    PubMed Central

    Bajaj, Chandrajit; Chen, Shun-Chuan; Rand, Alexander

    2011-01-01

    In order to compute polarization energy of biomolecules, we describe a boundary element approach to solving the linearized Poisson-Boltzmann equation. Our approach combines several important features including the derivative boundary formulation of the problem and a smooth approximation of the molecular surface based on the algebraic spline molecular surface. State of the art software for numerical linear algebra and the kernel independent fast multipole method is used for both simplicity and efficiency of our implementation. We perform a variety of computational experiments, testing our method on a number of actual proteins involved in molecular docking and demonstrating the effectiveness of our solver for computing molecular polarization energy. PMID:21660123

  15. Generalized energy-based fragmentation approach and its applications to macromolecules and molecular aggregates.

    PubMed

    Li, Shuhua; Li, Wei; Ma, Jing

    2014-09-16

    Conspectus The generalized energy-based fragmentation (GEBF) approach provides a very simple way of approximately evaluating the ground-state energy or properties of a large system in terms of ground-state energies of various small "electrostatically embedded" subsystems, which can be calculated with any traditional ab initio quantum chemistry (X) method (X = Hartree-Fock, density functional theory, and so on). Due to its excellent parallel efficiency, the GEBF approach at the X theory level (GEBF-X) allows full quantum mechanical (QM) calculations to be accessible for systems with hundreds and even thousands of atoms on ordinary workstations. The implementation of the GEBF approach at various theoretical levels can be easily done with existing quantum chemistry programs. This Account reviews the methodology, implementation, and applications of the GEBF-X approach. This method has been successfully applied to optimize the structures of various large systems including molecular clusters, polypeptides, proteins, and foldamers. Such investigations could allow us to elucidate the origin and nature of the cooperative interaction in secondary structures of long peptides or the driving force of the self-assembly processes of aromatic oligoamides. These GEBF-based QM calculations reveal that the structures and stability of various complex systems result from a subtle balance of many types of noncovalent interactions such as hydrogen bonding and van der Waals interactions. The GEBF-based ab initio molecular dynamics (AIMD) method also allows the investigation of dynamic behaviors of large systems on the order of tens of picoseconds. It was demonstrated that the conformational dynamics of two model peptides predicted by GEBF-based AIMD are noticeably different from those predicted by the classical force field MD method. With the target of extending QM calculations to molecular aggregates in the condensed phase, we have implemented the GEBF-based multilayer hybrid models

  16. Outcome-based profiling of astrocytic tumours identifies prognostic gene expression signatures which link molecular and morphology-based pathology.

    PubMed

    Beetz, Christian; Bergner, Sven; Brodoehl, Stefan; Brodhun, Michael; Ewald, Christian; Kalff, Rolf; Krüger, Jutta; Patt, Stephan; Kiehntopf, Michael; Deufel, Thomas

    2006-11-01

    Astrocytomas are intracranial malignancies for which invasive growth and high motility of tumour cells preclude total resection; the tumours usually recur in a more aggressive and, eventually, lethal form. Clinical outcome is highly variable and the accuracy of morphology-based prognostic statements is limited. In order to identify novel molecular markers for prognosis we obtained expression profiles of: i) tumours associated with particularly long recurrence-free intervals, ii) tumours which led to rapid patient death, and iii) tumour-free control brain. Unsupervised data analysis completely separated the three sample entities indicating a strong impact of the selection criteria on general gene expression. Consequently, significant numbers of specifically expressed genes could be identified for each entity. An extended set of tumours was then investigated by RT-PCR targeting 12 selected genes. Data from these experiments were summarised into a sample-specific index which assigns tumours to high- and low-risk groups as successfully as does morphology-based grading. Moreover, this index directly correlates with definite survival suggesting that integrated gene expression data allow individualised prognostic statements. We also analysed localisation of selected marker transcripts by in situ hybridization. Our finding of cell-specificity for some of these outcome-determining genes relates global expression data to the presence of morphological correlates of tumour behaviour and, thus, provides a link between morphology-based and molecular pathology. Our identification of expression signatures that are associated individually with clinical outcome confirms the prognostic relevance of gene expression data and, thus, represents a step towards eventually implementing molecular diagnosis into clinical practice in neuro-oncology.

  17. Molecular engineering of Schiff-base linked covalent polymers with diverse topologies by gas-solid interface reaction.

    PubMed

    Liu, Xuan-He; Guan, Cui-Zhong; Zheng, Qing-Na; Wang, Dong; Wan, Li-Jun

    2015-03-14

    The design and construction of molecular nanostructures with tunable topological structures are great challenges in molecular nanotechnology. Herein, we demonstrate the molecular engineering of Schiff-base bond connected molecular nanostructures. Building module construction has been adopted to modulate the symmetry of resulted one dimensional (1D) and two dimensional (2D) polymers. Specifically, we have designed and constructed 1D linear and zigzag polymers, 2D hexagonal and chessboard molecular nanostructures by varying the number of reactive sites and geometry and symmetry of precursors. It is demonstrated that high-quality conjugated polymers can be fabricated by using gas-solid interface reaction. The on-demanding synthesis of polymeric architectures with diverse topologies paves the way to fabricate molecular miniature devices with various desired functionalities.

  18. DNA base pair hybridization and water-mediated metastable structures studied by molecular dynamics simulations.

    PubMed

    Qi, Wenpeng; Song, Bo; Lei, Xiaoling; Wang, Chunlei; Fang, Haiping

    2011-11-08

    The base pair hybridization of a DNA segment was studied using molecular dynamics simulation. The results show the obvious correlation between the probability of successful hybridization and the accessible surface area to water of two successive base pairs, including the unpaired base pair adjacent to paired base pair and this adjacent paired base pair. Importantly, two metastable structures in an A-T base pair were discovered by the analysis of the free energy landscape. Both structures involved addition of a water molecule to the linkage between the two nucleobases in one base pair. The existence of the metastable structures provide potential barriers to the Watson-Crick base pair, and numerical simulations show that those potential barriers can be surmounted by thermal fluctuations at higher temperatures. These studies contribute an important step toward the understanding of the mechanism in DNA hybridization, particularly the effect of temperature on DNA hybridization and polymerase chain reaction. These observations are expected to be helpful for facilitating experimental bio/nanotechnology designs involving fast hybridization.

  19. 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.

  20. Surface plasmon resonance sensor based on magnetic molecularly imprinted polymers amplification for pesticide recognition.

    PubMed

    Yao, Gui-Hong; Liang, Ru-Ping; Huang, Chun-Fang; Wang, Ying; Qiu, Jian-Ding

    2013-12-17

    We reported here a method to enhance detection sensitivity in surface plasmon resonance (SPR) spectroscopy integrated with a surface molecular imprinting recognition system and employing magnetic molecular imprinting polymer nanoparticles for amplifying SPR response. The proposed magnetic molecular imprinting polymer was designed by self-polymerization of dopamine on the Fe3O4 NPs surface in weak base aqueous solution in the presence of template chlorpyrifos (CPF). The imprinted Fe3O4@polydopamine nanoparticles (Fe3O4@PDA NPs) were characterized by Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, and transmission electron microscopy. The biosensor showed a good linear relationship between the SPR angle shift and the chlorpyrifos concentration over a range from 0.001 to 10 μM with a detection limit of 0.76 nM. A significant increase in sensitivity was therefore afforded through the use of imprinted Fe3O4@PDA NPs as an amplifier, and meanwhile, the imprinted Fe3O4@PDA NPs had an excellent recognition capacity to chlorpyrifos over other pesticides. The excellent sensitivity and selectivity and high stability of the designed biosensor make this magnetic imprinted Fe3O4@PDA NP an attractive recognition element for various SPR sensors for detecting pesticide residuals and other environmentally deleterious chemicals.

  1. 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.

  2. All-optical integrated logic operations based on chemical communication between molecular switches.

    PubMed

    Silvi, Serena; Constable, Edwin C; Housecroft, Catherine E; Beves, Jonathon E; Dunphy, Emma L; Tomasulo, Massimiliano; Raymo, Françisco M; Credi, Alberto

    2009-01-01

    Molecular logic gates process physical or chemical "inputs" to generate "outputs" based on a set of logical operators. We report the design and operation of a chemical ensemble in solution that behaves as integrated AND, OR, and XNOR gates with optical input and output signals. The ensemble is composed of a reversible merocyanine-type photoacid and a ruthenium polypyridine complex that functions as a pH-controlled three-state luminescent switch. The light-triggered release of protons from the photoacid is used to control the state of the transition-metal complex. Therefore, the two molecular switching devices communicate with one another through the exchange of ionic signals. By means of such a double (optical-chemical-optical) signal-transduction mechanism, inputs of violet light modulate a luminescence output in the red/far-red region of the visible spectrum. Nondestructive reading is guaranteed because the green light used for excitation in the photoluminescence experiments does not affect the state of the gate. The reset is thermally driven and, thus, does not involve the addition of chemicals and accumulation of byproducts. Owing to its reversibility and stability, this molecular device can afford many cycles of digital operation.

  3. 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

  4. 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.

  5. A continuum breakdown parameter based on the characteristic function of the molecular velocity distribution

    NASA Astrophysics Data System (ADS)

    Alamatsaz, Arghavan; Venkattraman, Ayyaswamy

    2014-11-01

    Rarefied flows characterized by Knudsen numbers (Kn) greater than 0.1 are frequently encountered in several applications including low-pressure, high speed and microscale flows and require computationally expensive molecular approaches such as direct simulation Monte Carlo (DSMC) to accurately capture the physical phenomena unique to these flows. However, most of these flows also contain regions where traditional inexpensive continuum techniques such as the Navier-Stokes (NS) equations are sufficiently accurate making a hybrid NS-DSMC approach attractive and optimal. Such a hybrid method typically requires a robust continuum breakdown parameter (CBP) to determine regions where each method should be applied. Historically, hybrid methods have used CBPs based on the macroscopic properties which are lower order moments of the molecular velocity distribution function (VDF) and their gradients which can have significant inaccuracies. In this work, we propose a novel CBP that utilizes all moments of the VDF by computing the characteristic function with limited computational overhead. We also compare the performance of this CBP using standard benchmark problems including structure of a normal shock wave and Fourier-Couette flow for various Kn from continuum to free-molecular.

  6. Molecular phylogeny of the lionfish genera Dendrochirus and Pterois (Scorpaenidae, Pteroinae) based on mitochondrial DNA sequences.

    PubMed

    Kochzius, Marc; Söller, Rainer; Khalaf, Maroof A; Blohm, Dietmar

    2003-09-01

    This study investigates the molecular phylogeny of seven lionfishes of the genera Dendrochirus and Pterois. MP, ML, and NJ phylogenetic analysis based on 964 bp of partial mitochondrial DNA sequences (cytochrome b and 16S rDNA) revealed two main clades: (1) "Pterois" clade (Pterois miles and Pterois volitans), and (2) "Pteropterus-Dendrochirus" clade (remainder of the sampled species). The position of Dendrochirus brachypterus either basal to the main clades or in the "Pteropterus-Dendrochirus" clade cannot be resolved. However, the molecular phylogeny did not support the current separation of the genera Pterois and Dendrochirus. The siblings P. miles and P. volitans are clearly separated and our results support the proposed allopatric or parapatric distribution in the Indian and Pacific Ocean. However, the present analysis cannot reveal if P. miles and P. volitans are separate species or two populations of a single species, because the observed separation in different clades can be either explained by speciation or lineage sorting. Molecular clock estimates for the siblings P. miles and P. volitans suggest a divergence time of 2.4-8.3 mya, which coincide with geological events that created vicariance between populations of the Indian and Pacific Ocean.

  7. 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

  8. Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites

    PubMed Central

    Floros, Dimitrios J.; Petras, Daniel; Kapono, Clifford A.; Melnik, Alexey V.; Ling, Tie-Jun; Knight, Rob; Dorrestein, Pieter C.

    2017-01-01

    Plants play an essential part in global carbon fixing through photosynthesis and are the primary food and energy source for humans. Understanding them thoroughly is therefore of highest interest for humanity. Advances in DNA and RNA sequencing and in protein and metabolite analysis allow the systematic description of plant composition at the molecular level. With imaging mass spectrometry, we can now add a spatial level, typically in the micrometer-to-centimeter range, to their compositions, essential for a detailed molecular understanding. Here we present an LC-MS based approach for 3D plant imaging, which is scalable and allows the analysis of entire plants. We applied this approach in a case study to pepper and tomato plants. Together with MS/MS spectra library matching and spectral networking, this non-targeted workflow provides the highest sensitivity and selectivity for the molecular annotations and imaging of plants, laying the foundation for studies of plant metabolism and plant-environment interactions. PMID:28405197

  9. Effect of molecular conformation on the mechanofluorochromic properties based on DDIF

    NASA Astrophysics Data System (ADS)

    Mai, Runsheng; Peng, Huojun; Meng, Yuying; Chang, Xinyue; Jiang, Yue; Gao, Jinwei; Zhou, Guofu; Liu, Jun-ming

    2017-07-01

    Mechanofluorochromic (MFC) materials are smart materials in that their absorption and/or emission can respond to mechanical stimuli. They have received much attention recently. Although there have been several new material systems designed, little work has been done regarding the influence of molecular conformation on MFC properties. Herein, to disclose the relationship between molecular conformation and MFC properties, two molecules based on a 6, 12-Dihydro-6, 12-diaza-indeno[1,2-b]fluorine (DDIF) building block with thienyl linker, BDDIF-Th and BDDIF-BTh, have been designed and synthesized. Optical and electrochemical properties have been studied by UV-vis spectrometer and cyclic voltammetry measurements. Weak aggregation-induced emission (AIE) phenomena were obtained in the tetrahydrofuran (THF)/water solution. MFC behaviors suggest that BDDIF-Th is more sensible to the external mechanical forces than BDDIF-BTh. The color change could be attributed to the appearance of new emission peak instead of a bathochromic or hypsochromic effect. Theoretical calculations reveal that MFC performance is highly related to the molecular conformation, meaning that the BDDIF-BTh with perpendicular conformation is more difficult to flatten than the comparatively planar BDDIF-Th.

  10. Potent Human Telomerase Inhibitors: Molecular Dynamic Simulations, Multiple Pharmacophore-Based Virtual Screening, and Biochemical Assays.

    PubMed

    Shirgahi Talari, Faezeh; Bagherzadeh, Kowsar; Golestanian, Sahand; Jarstfer, Michael; Amanlou, Massoud

    2015-12-28

    Telomere maintenance is a universal cancer hallmark, and small molecules that disrupt telomere maintenance generally have anticancer properties. Since the vast majority of cancer cells utilize telomerase activity for telomere maintenance, the enzyme has been considered as an anticancer drug target. Recently, rational design of telomerase inhibitors was made possible by the determination of high resolution structures of the catalytic telomerase subunit from a beetle and subsequent molecular modeling of the human telomerase complex. A hybrid strategy including docking, pharmacophore-based virtual screening, and molecular dynamics simulations (MDS) were used to identify new human telomerase inhibitors. Docking methodology was applied to investigate the ssDNA telomeric sequence and two well-known human telomerase inhibitors' (BIBR1532 and MST-312) modes of interactions with hTERT TEN domain. Subsequently molecular dynamic simulations were performed to monitor and compare hTERT TEN domain, TEN-ssDNA, TEN-BIBR1532, TEN-MST-312, and TEN-ssDNA-BIBR1532 behavior in a dynamic environment. Pharmacophore models were generated considering the inhibitors manner in the TEN domain anchor site. These exploratory studies identified several new potent inhibitors whose IC50 values were generated experimentally in a low micromolar range with the aid of biochemical assays, including both the direct telomerase and the telomeric repeat amplification protocol (TRAP) assays. The results suggest that the current models of human telomerase are useful templates for rational inhibitor design.

  11. Multiple-Time Step Ab Initio Molecular Dynamics Based on Two-Electron Integral Screening.

    PubMed

    Fatehi, Shervin; Steele, Ryan P

    2015-03-10

    A multiple-timestep ab initio molecular dynamics scheme based on varying the two-electron integral screening method used in Hartree-Fock or density functional theory calculations is presented. Although screening is motivated by numerical considerations, it is also related to separations in the length- and timescales characterizing forces in a molecular system: Loose thresholds are sufficient to describe fast motions over short distances, while tight thresholds may be employed for larger length scales and longer times, leading to a practical acceleration of ab initio molecular dynamics simulations. Standard screening approaches can lead, however, to significant discontinuities in (and inconsistencies between) the energy and gradient when the screening threshold is loose, making them inappropriate for use in dynamics. To remedy this problem, a consistent window-screening method that smooths these discontinuities is devised. Further algorithmic improvements reuse electronic-structure information within the dynamics step and enhance efficiency relative to a naı̈ve multiple-timestepping protocol. The resulting scheme is shown to realize meaningful reductions in the cost of Hartree-Fock and B3LYP simulations of a moderately large system, the protonated sarcosine/glycine dipeptide embedded in a 19-water cluster.

  12. Non-destructive staging of barley reproductive development for molecular analysis based upon external morphology.

    PubMed

    Gómez, José Fernández; Wilson, Zoe A

    2012-06-01

    A prerequisite to study the molecular genetic pathways of pollen and anther development is an accurate staging system for reproductive development. However in barley, floret formation occurs mainly within the pseudostem, which makes the observation of floret development and access to the floret particularly difficult without dissecting the plant. Thus selecting stages for molecular analysis cannot be done non-destructively. A staging method has therefore been developed for barley in order to define the relationship between readily detectable growth points and reproductive development, to provide a clear key to enable accurate selection of reproductive material. Initial staging followed the traditional Zadoks decimal system, with minor adaptations to stages 31-34 and stage 37. The later stages, from 37 onward, were replaced by growth staging based upon the last flag elongation (LFE) and the position occupied by the spike within the pseudostem. Spike size could be readily predicted by using the staging system incorporating Zadoks stages 31-37, supplemented with substages and by LFE staging to improve accuracy. The different spike sizes, as well as the LFE stages, showed a clear relationship to events occurring within the anther, as confirmed by light microscopy of the anthers. The defined relationship between spike size and development to anther development now makes possible the accurate prediction of anther and pollen progression by external staging. This, therefore, provides a mechanism for non-destructive selection of material for analysis that is critical for the molecular characterization of genes in anther and pollen development.

  13. 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

    2015-08-04

    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.

  14. "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.

  15. Synthesis and Self-Assembly Behaviors of Polyhedral Oligomeric Silsesquioxane Based Giant Molecular Shape Amphiphiles

    NASA Astrophysics Data System (ADS)

    Yue, Kan; Yu, Xinfei; Liu, Chang; Zhang, Wen-Bin; Cheng, Stephen

    2013-03-01

    Recently, our group has focus on the synthesis and characterization of novel giant molecular shape amphiphiles (GMSAs) based on functionalized molecular nanoparticles (MNPs), such as polyhedral oligomeric silsesquioxane (POSS), tethered with polymeric tails. A general synthetic method via the combination of sequential ?click? reactions has been developed and several model GMSAs with various tail lengths and distinct molecular topologies, which can be referred as the ?giant surfactants?, ?giant lipids?, ?giant gemini surfactants?, and ?giant bolaform surfactants? etc., have been demonstrated. Studies on their self-assembly behaviors in the bulk have revealed the formation of different ordered mesophase structures with feature sizes around 10 nanometers, which have been investigated in detail by small angle X-ray scattering (SAXS) technique and transmission electron microscopy (TEM). These findings have general implications on understanding the underlying principles of self-assembly behaviors of GMSAs, and might have potential applications in nano-patterning technology. This work is supported by NSF (DMR-0906898) and the Joint-Hope Foundation.

  16. 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

  17. PBCA-based Polymeric Microbubbles for Molecular Imaging and Drug Delivery

    PubMed Central

    Shi, Yang; Liu, Mengjiao; Dasgupta, Anshuman; Pathak, Vertika; Ojha, Tarun; Fokong, Stanley; Wu, Zhuojun; van Zandvoort, Marc; Iranzo, Olga; Kuehne, Alexander; Pich, Andrij; Kiessling, Fabian; Lammers, Twan

    2017-01-01

    Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated drug delivery. Molecular imaging of angiogenic tumor blood vessels and inflamed atherosclerotic endothelium is performed by modifying the surface of PBCA MB with peptides and antibodies recognizing E-selectin and VCAM-1. Stable and inertial cavitation of PBCA MB enables sonoporation and permeabilization of blood vessels in tumors and in the brain, which can be employed for direct and indirect drug delivery. Direct drug delivery is based on US-induced release of (model) drug molecules from the MB shell. Indirect drug delivery refers to US- and MB-mediated enhancement of extravasation and penetration of co-administered drugs and drug delivery systems. These findings are in line with recently reported pioneering proof-of-principle studies showing the usefulness of (phospholipid) MB for molecular US imaging and sonoporation-enhanced drug delivery in patients. They aim to exemplify the potential and the broad applicability of combining MB with US to improve disease diagnosis and therapy. PMID:28279799

  18. Mass-spectrometry-based molecular characterization of extracellular vesicles: lipidomics and proteomics.

    PubMed

    Kreimer, Simion; Belov, Arseniy M; Ghiran, Ionita; Murthy, Shashi K; Frank, David A; Ivanov, Alexander R

    2015-06-05

    This review discusses extracellular vesicles (EVs), which are submicron-scale, anuclear, phospholipid bilayer membrane enclosed vesicles that contain lipids, metabolites, proteins, and RNA (micro and messenger). They are shed from many, if not all, cell types and are present in biological fluids and conditioned cell culture media. The term EV, as coined by the International Society of Extracellular Vesicles (ISEV), encompasses exosomes (30-100 nm in diameter), microparticles (100-1000 nm), apoptotic blebs, and other EV subsets. EVs have been implicated in cell-cell communication, coagulation, inflammation, immune response modulation, and disease progression. Multiple studies report that EV secretion from disease-affected cells contributes to disease progression, e.g., tumor niche formation and cancer metastasis. EVs are attractive sources of biomarkers due to their biological relevance and relatively noninvasive accessibility from a range of physiological fluids. This review is focused on the molecular profiling of the protein and lipid constituents of EVs, with emphasis on mass-spectrometry-based "omic" analytical techniques. The challenges in the purification and molecular characterization of EVs, including contamination of isolates and limitations in sample quantities, are discussed along with possible solutions. Finally, the review discusses the limited but growing investigation of post-translational modifications of EV proteins and potential strategies for future in-depth molecular characterization of EVs.

  19. Improved student linkage of Mendelian and molecular genetic concepts through a yeast-based laboratory module.

    PubMed

    Wolyniak, Michael J

    2013-01-01

    A study of modern genetics requires students to successfully unite the principles of Mendelian genetics with the functions of DNA. Traditional means of teaching genetics are often successful in teaching Mendelian and molecular ideas but not in allowing students to see how the two subjects relate. The laboratory module presented here attempts to present classical and molecular genetic concepts together as an inquiry-based exploration appropriate for high school or introductory undergraduate students. Using the non-essential APQ12 gene in the budding yeast Saccharomyces cerevisiae, students perform PCR, selective growth, and sporulation experiments to establish the ploidy and APQ12 zygosity of a series of unknown strains. Each experiment contributes data to characterize the unknown strains, but complete characterization is not possible without assimilating the data from all of the experiments. The module allows students to consider concepts normally introduced and emphasized in Mendelian genetics and explore them using molecular and experimental tools. Comparison of pre-module and post-module assessment surveys show an increase in student ability to link Mendelian concepts to experimental procedures relying on DNA analysis. The development of modules such as these provides students of all backgrounds with the tools to engage the complexities and issues that constitute modern principles of inheritance.

  20. Analysis of molecular expression patterns and integration with other knowledge bases using probabilistic Bayesian network models

    SciTech Connect

    Moler, Edward J.; Mian, I.S.

    2000-03-01

    How can molecular expression experiments be interpreted with greater than ten to the fourth measurements per chip? How can one get the most quantitative information possible from the experimental data with good confidence? These are important questions whose solutions require an interdisciplinary combination of molecular and cellular biology, computer science, statistics, and complex systems analysis. The explosion of data from microarray techniques present the problem of interpreting the experiments. The availability of large-scale knowledge bases provide the opportunity to maximize the information extracted from these experiments. We have developed new methods of discovering biological function, metabolic pathways, and regulatory networks from these data and knowledge bases. These techniques are applicable to analyses for biomedical engineering, clinical, and fundamental cell and molecular biology studies. Our approach uses probabilistic, computational methods that give quantitative interpretations of data in a biological context. We have selected Bayesian statistical models with graphical network representations as a framework for our methods. As a first step, we use a nave Bayesian classifier to identify statistically significant patterns in gene expression data. We have developed methods which allow us to (a) characterize which genes or experiments distinguish each class from the others, (b) cross-index the resulting classes with other databases to assess biological meaning of the classes, and (c) display a gross overview of cellular dynamics. We have developed a number of visualization tools to convey the results. We report here our methods of classification and our first attempts at integrating the data and other knowledge bases together with new visualization tools. We demonstrate the utility of these methods and tools by analysis of a series of yeast cDNA microarray data and to a set of cancerous/normal sample data from colon cancer patients. We discuss

  1. 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.

  2. 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

  3. Rayleigh light scattering properties of atmospheric molecular clusters consisting of sulfuric acid and bases.

    PubMed

    Elm, Jonas; Norman, Patrick; Mikkelsen, Kurt V

    2015-06-28

    The Rayleigh light scattering properties of (H2SO4)a(NH3)b and (H2SO4)a((CH3)2NH)b atmospheric molecular clusters have been investigated using a response theory approach. Using density functional theory the molecular structures and stepwise formation free energies of clusters with a and b up to 4 have been re-investigated. The Rayleigh scattering intensities are calculated from the dipole polarizability tensor α using the CAM-B3LYP functional by applying linear response methods. The intrinsic scattering properties of (H2SO4)a(NH3)b and (H2SO4)a((CH3)2NH)b indicate that amine containing clusters scatter light significantly more efficiently then their ammonia containing counterparts. Using the Atmospheric Cluster Dynamics Code (ACDC) the steady state cluster concentrations are estimated and the effective scattering is calculated. The effective scattering is shown to be highly dependent on the estimated concentrations and indicates that there exist competitive pathways, such as nucleation and coagulation, which influence the cluster distributions. The frequency dependence of the scattering is found to depend on the cluster composition and show increased responses when clusters contain more bases than acid molecules. Based on structures obtained using semi-empirical molecular dynamics simulations the Rayleigh scattering properties of clusters with up to 20 acid-base pairs are evaluated. This study represents the first step towards gaining a fundamental understanding of the scattering properties of small atmospheric clusters in the ambient atmosphere.

  4. Detergent-dispersant additives based on high-molecular-weight alkylphenols

    SciTech Connect

    Kulieva, K.N.; Namazova, I.I.; Ismailova, N.D.; Dorokhina, I.V.

    1988-09-01

    This article describes the synthesis and investigation of Mannich bases produced for alkylphenols, obtained in turn from ethylene oligomers. These oligomers are the still bottoms from distillation products of high-temperature oligomerization of ethylene in the presence of triethylaluminum. Two narrow cuts obtained from the distillation of oligomer fraction were used to study the influence of ethylene oligomer molecular weight on the properties of the additives. The additives were blended in DS-11 oil to evaluate their detergency-dispersancy and other properties. Comparison blends were made with succinimide additives based on the same ethylene oligomers. The Mannich bases give improvements in the oxidation resistance, anticorrosion properties, and detergency-dispersancy of the DS-11 diesel oil.

  5. Matched molecular pair-based data sets for computer-aided medicinal chemistry.

    PubMed

    Hu, Ye; de la Vega de León, Antonio; Zhang, Bijun; Bajorath, Jürgen

    2014-01-01

    Matched molecular pairs (MMPs) are widely used in medicinal chemistry to study changes in compound properties including biological activity, which are associated with well-defined structural modifications. Herein we describe up-to-date versions of three MMP-based data sets that have originated from in-house research projects. These data sets include activity cliffs, structure-activity relationship (SAR) transfer series, and second generation MMPs based upon retrosynthetic rules. The data sets have in common that they have been derived from compounds included in the ChEMBL database (release 17) for which high-confidence activity data are available. Thus, the activity data associated with MMP-based activity cliffs, SAR transfer series, and retrosynthetic MMPs cover the entire spectrum of current pharmaceutical targets. Our data sets are made freely available to the scientific community.

  6. Synthesis and molecular characterization of chitosan based polyurethane elastomers using aromatic diisocyanate.

    PubMed

    Zia, Khalid Mahmood; Anjum, Sohail; Zuber, Mohammad; Mujahid, Muhammad; Jamil, Tahir

    2014-05-01

    The present research work was performed to synthesize a new series of chitosan based polyurethane elastomers (PUEs) using poly(ɛ-caprolactone) (PCL). The chitosan based PUEs were prepared by step-growth polymerization technique using poly(ɛ-caprolactone) (PCL) and 2,4-toluene diisocyanate (TDI). In the second step the PU prepolymer was extended with different mole ratios of chitosan and 1,4-butane diol (BDO). Molecular engineering was carried out during the synthesis. The conventional spectroscopic characterization of the synthesized samples using FT-IR confirms the existence of the proposed chitosan based PUEs structure. Internal morphology of the prepared PUEs was studied using SEM analysis. The SEM images confirmed the incorporation of chitosan molecules into the PU backbone. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Structure and dynamics of acetate anion-based ionic liquids from molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Chandran, Aneesh; Prakash, Karthigeyan; Senapati, Sanjib

    2010-08-01

    Acetate anion-based ionic liquids (ILs) have found wide range of applications. The microstructure and dynamics of this IL family have not been clearly understood yet. We report molecular dynamics simulation results of three acetate anion-based ionic liquids that encompass the most common IL cations. Simulations are performed based on a set of proposed force field parameters for IL acetate anion which can be combined with existing parameters for IL cations to simulate large variety of ILs. The computed liquid density and IR spectral data for [BMIM][Ac] are found to match very well with available experimental results. The strong amino-group-associated interactions in [TMG][Ac] are seen to bring about higher cohesive energy density, stronger ion packing, and more restricted translational and rotational mobilities of the constituent ions. The IL anions are found to track the cation movements in all systems, implying that ions in ILs travel in pairs or clusters.

  8. Zeolite molecular sieves have dramatic acid-base effects on enzymes in nonaqueous media.

    PubMed

    Fontes, Nuno; Partridge, Johann; Halling, Peter J; Barreiros, Susana

    2002-02-05

    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.

  9. Mass Spectrometry-based Approaches to Understand the Molecular Basis of Memory

    NASA Astrophysics Data System (ADS)

    Pontes, Arthur; de Sousa, Marcelo

    2016-10-01

    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 enable the identification and quantification of thousand 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.

  10. Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small-Molecular-Target-Based Photodynamic Therapy.

    PubMed

    Chen, Juan-Juan; Huang, Yi-Zhen; Song, Mei-Ru; Zhang, Zhi-Hong; Xue, Jin-Ping

    2017-09-21

    Small-molecular-target-based photodynamic therapy-a promising targeted anticancer strategy-was developed by conjugating zinc(II) phthalocyanine with a small-molecular-target-based anticancer drug. To prevent self-aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di-substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell-based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC50 values as low as 8 nm under a light dose of 1.5 J cm(-2) ). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR-overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Ontology based molecular signatures for immune cell types via gene expression analysis.

    PubMed

    Meehan, Terrence F; Vasilevsky, Nicole A; Mungall, Christopher J; Dougall, David S; Haendel, Melissa A; Blake, Judith A; Diehl, Alexander D

    2013-08-30

    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. 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. 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.

  12. Sinocurculigo, a New Genus of Hypoxidaceae from China Based on Molecular and Morphological Evidence

    PubMed Central

    Chen, Li-Jun; Xiao, Xin-Ju; Zheng, Yu-Yun; Cai, Jing; Zhai, Jun-Wen; Zhang, Guo-Qiang; Liu, Zhong-Jian

    2012-01-01

    Background The monocot family Hypoxidaceae consists of nine genera with nearly 200 species. They occur mostly in the Southern Hemisphere with only a few species in the Northern Hemisphere, of which three genera, Hypoxis, Molineria, and Curculigo, with eight species are distributed in China. Recently, we have found a hypoxid-like plant in China that is quite different in floral structure from any of the three genera and even of the known taxa in Hypoxidaceae. Methodology/Principal Findings In addition to morphological analysis, we performed maximum parsimony, maximum likelihood, and Bayesian inference analyses based on fragments of the chloroplast matK and rbcL genes of 60 taxa in 12 families representing all major clades of the Hypoxidaceae alliance. Results showed that Hypoxidaceae is monophyletic and and that the new plant belongs to it, forming a distinct clade within the family Hypoxidaceae as a sister of Molineria. Phylogeny of the Hypoxidaceae family was constructed based on a combined matrix of the chloroplast rbcL, trnS-G, and trnL-F regions of 59 taxa in Hypoxidaceae and its alliance. Findings of the molecular investigation is consistent with those of the morphological analysis. Conclusions/Significance Based on the results of our molecular and morphological analyses in the present study, we propose a new genus, Sinocurculigo. PMID:22761711

  13. Mass Spectrometry-Based Approaches to Understand the Molecular Basis of Memory.

    PubMed

    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.

  14. 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

  15. Physical and molecular bases of protein thermal stability and cold adaptation.

    PubMed

    Pucci, Fabrizio; Rooman, Marianne

    2017-02-01

    The molecular bases of thermal and cold stability and adaptation, which allow proteins to remain folded and functional in the temperature ranges in which their host organisms live and grow, are still only partially elucidated. Indeed, both experimental and computational studies fail to yield a fully precise and global physical picture, essentially because all effects are context-dependent and thus quite intricate to unravel. We present a snapshot of the current state of knowledge of this highly complex and challenging issue, whose resolution would enable large-scale rational protein design.

  16. Molecular Recognition of DNA. Synthesis of Novel Bases for Triple Helix Formation

    DTIC Science & Technology

    1991-01-01

    to the purine strand in the major groove of the Watson - Crick double helical DNA (TAT, C+GC triplets). Purine oligonucleotides bind antiparallel to...R&T Code 4135018 S MAy 05 199411 "Molecular Recognition of DNA . Synthesis of Novel Bases for Triple Helix Formation" Peter B. Dervan cv _California...035 T"IQA""D PART I A) Completed work (1988-91) Triple Helix Formation by Oligonucleotides on DNA Extended to the Physiological pH Range. T. J. Povsic

  17. CL-20/DNB co-crystal based PBX with PEG: molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Zhang, Jiang; Gao, Pei; Xiao, Ji Jun; Zhao, Feng; Xiao, He Ming

    2016-12-01

    Molecular dynamics simulation was carried out for CL-20/DNB co-crystal based PBX (polymer-bonded explosive) blended with polymer PEG (polyethylene glycol). In this paper, the miscibility of the PBX models is investigated through the calculated binding energy. Pair correlation function (PCF) analysis is applied to study the interaction of the interface structures in the PBX models. The mechanical properties of PBXs are also discussed to understand the change of the mechanical properties after adding the polymer. Moreover, the calculated diffusion coefficients of the interfacial explosive molecules are used to discuss the dispersal ability of CL-20 and DNB molecules in the interface layer.

  18. 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

  19. 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.

  20. [Molecular identification of 15 species of Ilex genus based on ITS sequence analysis ].

    PubMed

    Yi, Fan; Han, Feng-ming; Peng, Yong

    2014-06-01

    To establish molecular method for identification of Ilex plants using the internal transcribed spacer(ITS) bar- code. DNA was extracted using centrifugal columnar kits. The ITS sequences of all experimental samples were amplified and sequenced using a pair of universal primers. The alignment and the phylogenetic tree were performed in MEGA5. 0. The length of ITS sequence in each species was 759 bp,in which there were 216 sites discrepancy. DNA barcoding technology based on ITS sequence can be used to identify plants of Ilex genus.