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Sample records for molecular based approach

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

    PubMed

    Fang, Tao; Jia, Junteng; Li, Shuhua

    2016-05-01

    The generalized energy-based fragmentation (GEBF) approach for molecular crystals with periodic boundary condition (PBC) (denoted as PBC-GEBF) is extended to allow vibrational spectra of molecular crystals to be easily computed at various theory levels. Within the PBC-GEBF approach, the vibrational frequencies of a molecular crystal can be directly evaluated from molecular quantum chemistry calculations on a series of nonperiodic molecular systems. With this approach, the vibrational spectra of molecular crystals can be calculated with much reduced computational costs at various theory levels, as compared to those required by the methods based on periodic electronic structure theory. By testing the performance of the PBC-GEBF method for two molecular crystals (CO2 and imidazole), we demonstrate that the PBC-GEBF approach can reproduce the results of the methods based on periodic electronic structure theory in predicting vibrational spectra of molecular crystals. We apply the PBC-GEBF method at second-order Møller-Plesset perturbation theory (PBC-GEBF-MP2 in short) to investigate the vibrational spectra of the urea and ammonia borane crystals. Our results show that the PBC-GEBF-MP2 method can provide quite accurate descriptions for the observed vibrational spectra of the two systems under study. PMID:27076120

  2. 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. PMID:26792102

  3. 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.

  4. 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

  5. Nanotubule and Tour Molecule Based Molecular Electronics: Suggestion for a Hybrid Approach

    NASA Technical Reports Server (NTRS)

    Srivastava, Deepak; Saini, Subhash (Technical Monitor)

    1998-01-01

    Recent experimental and theoretical attempts and results indicate two distinct broad pathways towards future molecular electronic devices and architectures. The first is the approach via Tour type ladder molecules and their junctions which can be fabricated with solution phase chemical approaches. Second are fullerenes or nanotubules and their junctions which may have better conductance, switching and amplifying characteristics but can not be made through well controlled and defined chemical means. A hybrid approach combining the two pathways to take advantage of the characteristics of both is suggested. Dimension and scale of such devices would be somewhere in between isolated molecule and nanotubule based devices but it maybe possible to use self-assembly towards larger functional and logicalunits.

  6. Predicting Molecular Targets for Small-Molecule Drugs with a Ligand-Based Interaction Fingerprint Approach.

    PubMed

    Cao, Ran; Wang, Yanli

    2016-06-20

    The computational prediction of molecular targets for small-molecule drugs remains a great challenge. Herein we describe a ligand-based interaction fingerprint (LIFt) approach for target prediction. Together with physics-based docking and sampling methods, we assessed the performance systematically by modeling the polypharmacology of 12 kinase inhibitors in three stages. First, we examined the capacity of this approach to differentiate true targets from false targets with the promiscuous binder staurosporine, based on native complex structures. Second, we performed large-scale profiling of kinase selectivity on the clinical drug sunitinib by means of computational simulation. Third, we extended the study beyond kinases by modeling the cross-inhibition of bromodomain-containing protein 4 (BRD4) for 10 well-established kinase inhibitors. On this basis, we made prospective predictions by exploring new kinase targets for the anticancer drug candidate TN-16, originally known as a colchicine site binder and microtubule disruptor. As a result, p38α was highlighted from a panel of 187 different kinases. Encouragingly, our prediction was validated by an in vitro kinase assay, which showed TN-16 as a low-micromolar p38α inhibitor. Collectively, our results suggest the promise of the LIFt approach in predicting potential targets for small-molecule drugs. PMID:26222196

  7. Perils of paediatric anaesthesia and novel molecular approaches: An evidence-based review

    PubMed Central

    Bajwa, Sukhminder Jit Singh; Anand, Smriti; Gupta, Hemant

    2015-01-01

    Evolution of anaesthesia has been largely helped by progress of evidence-based medicine. In spite of many advancements in anaesthesia techniques and availability of newer and safer drugs, much more needs to be explored scientifically for the development of anaesthesia. Over the last few years, the notion that the actions of the anaesthesiologist have only immediate or short-term consequences has largely been challenged. Evidences accumulated in the recent years have shown that anaesthesia exposure may have long-term consequences particularly in the extremes of ages. However, most of the studies conducted so far are in vitro or animal studies, the results of which have been extrapolated to humans. There have been confounding evidences linking anaesthesia exposure in the developing brain with poor neurocognitive outcome. The results of animal studies and human retrospective studies have raised concern over the potential detrimental effects of general anaesthetics on the developing brain. The purpose of this review is to highlight the long-term perils of anaesthesia in the very young and the potential of improving anaesthesia delivery with the novel molecular approaches. PMID:26019351

  8. Ion Pair in Extreme Aqueous Environments, Molecular-Based and Electric Conductance Approaches

    SciTech Connect

    Chialvo, Ariel A; Gruszkiewicz, Miroslaw {Mirek} S; Simonson, J Michael {Mike}; Palmer, Donald; Cole, David R

    2009-01-01

    We determine by molecular-based simulation the density profiles of the Na+!Cl! ion-pair association constant in steam environments along three supercritical isotherms to interrogate the behavior of ion speciation in dilute aqueous solutions at extreme conditions. Moreover, we describe a new ultra-sensitive flow-through electric conductance apparatus designed to bridge the gap between the currently lowest steam-density conditions at which we are experimentally able to attain electric conductance measurements and the theoretically-reachable zero-density limit. Finally, we highlight important modeling challenges encountered near the zero-density limit and discuss ways to overcome them.

  9. Comparison of PCR-based approaches to molecular epidemiologic analysis of Clostridium difficile.

    PubMed Central

    Collier, M C; Stock, F; DeGirolami, P C; Samore, M H; Cartwright, C P

    1996-01-01

    Representative isolates of the 10 serogroups of Clostridium difficile and 39 clinical isolates (30 toxigenic and 9 nontoxigenic), including 5 isolates from a confirmed nosocomial outbreak, were analyzed by using two previously described arbitrary-primer PCR (AP-PCR) molecular typing methodologies (AP-PG05 and AP-ARB11) and PCR ribotyping. The two AP-PCR methods investigated gave comparable results; AP-PG05 and AP-ARB11 identified 8 and 7 groups among the serogroup isolates and classified the clinical isolates into 21 and 20 distinct groups, respectively. PCR ribotyping also identified 8 unique groups among the serogroup isolates but classified the clinical isolates into 23 groups. In addition, when results obtained by the PCR methods were compared with typing data generated by pulsed-field gel electrophoresis (PFGE), PCR ribotyping and PFGE were found to be in agreement for 83% (29 of 35) of isolates typeable by both techniques while AP-PG05 was in agreement with PFGE for 60% (20 of 33) and AP-ARB11 was in agreement with PFGE for only 44% (17 of 36). These results indicate that PCR ribotyping is a more discriminatory approach than AP-PCR for typing C. difficile and, furthermore, that this technique generates results that are in higher concordance with those obtained by using an established method for differentiating isolates of this organism on a molecular level than are results generated by using AP-PCR. PMID:8727893

  10. On the optimal design of molecular sensing interfaces with lipid bilayer assemblies - A knowledge based approach

    NASA Astrophysics Data System (ADS)

    Siontorou, Christina G.

    2012-12-01

    Biosensors are analytic devices that incorporate a biochemical recognition system (biological, biologicalderived or biomimic: enzyme, antibody, DNA, receptor, etc.) in close contact with a physicochemical transducer (electrochemical, optical, piezoelectric, conductimetric, etc.) that converts the biochemical information, produced by the specific biological recognition reaction (analyte-biomolecule binding), into a chemical or physical output signal, related to the concentration of the analyte in the measuring sample. The biosensing concept is based on natural chemoreception mechanisms, which are feasible over/within/by means of a biological membrane, i.e., a structured lipid bilayer, incorporating or attached to proteinaceous moieties that regulate molecular recognition events which trigger ion flux changes (facilitated or passive) through the bilayer. The creation of functional structures that are similar to natural signal transduction systems, correlating and interrelating compatibly and successfully the physicochemical transducer with the lipid film that is self-assembled on its surface while embedding the reconstituted biological recognition system, and at the same time manage to satisfy the basic conditions for measuring device development (simplicity, easy handling, ease of fabrication) is far from trivial. The aim of the present work is to present a methodological framework for designing such molecular sensing interfaces, functioning within a knowledge-based system built on an ontological platform for supplying sub-systems options, compatibilities, and optimization parameters.

  11. Important issues facing model-based approaches to tunneling transport in molecular junctions

    NASA Astrophysics Data System (ADS)

    Bâldea, Ioan

    Extensive studies on thin films indicated a generic cubic current-voltage $I-V$ dependence as a salient feature of charge transport by tunneling. A quick glance at $I-V$ data for molecular junctions suggests a qualitatively similar behavior. This would render model-based studies almost irrelevant, since, whatever the model, its parameters can always be adjusted to fit symmetric (asymmetric) $I-V$ curves characterized by two (three) expansion coefficients. Here, we systematically examine popular models based on tunneling barrier or tight-binding pictures and demonstrate that, for a quantitative description at biases of interest ($V$ slightly higher than the transition voltage $V_t$), cubic expansions do not suffice. A detailed collection of analytical formulae as well as their conditions of applicability are presented to facilitate experimentalists colleagues to process and interpret their experimental data by obtained by measuring currents in molecular junctions. We discuss in detail the limits of applicability of the various models and emphasize that uncritically adjusting model parameters to experiment may be unjustified because the values deduced in this way may fall in ranges rendering a specific model invalid or incompatible to ab initio estimates. We exemplify with the benchmark case of oligophenylene-based junctions, for which results of ab initio quantum chemical calculations are also reported. As a specific issue, we address the impact of the spatial potential profile and show that it is not notable up to biases V somewhat larger than V_t, unlike at higher biases, where it may be responsible for negative differential resistance effects.

  12. Important issues facing model-based approaches to tunneling transport in molecular junctions.

    PubMed

    Bâldea, Ioan

    2015-08-21

    Extensive studies on thin films indicated a generic cubic current-voltage I-V dependence as a salient feature of charge transport by tunneling. A quick glance at I-V data for molecular junctions suggests a qualitatively similar behavior. This would render model-based studies almost irrelevant, since, whatever the model, its parameters can always be adjusted to fit symmetric (asymmetric) I-V curves characterized by two (three) expansion coefficients. Here, we systematically examine popular models based on tunneling barriers or tight-binding pictures and demonstrate that, for a quantitative description at biases of interest (V slightly higher than the transition voltage Vt), cubic expansions do not suffice. A detailed collection of analytical formulae as well as their conditions of applicability is presented to facilitate experimentalist colleagues to process and interpret their experimental data obtained by measuring currents in molecular junctions. We discuss in detail the limits of applicability of the various models and emphasize that uncritically adjusting the model parameters to experiment may be unjustified because the values deduced in this way may fall in ranges rendering a specific model invalid or incompatible to ab initio estimates. We exemplify with the benchmark case of oligophenylene-based junctions, for which the results of ab initio quantum chemical calculations are also reported. As a specific issue, we address the impact of the spatial potential profile and show that it is not notable up to biases V ≳ Vt, unlike at higher biases, where it may be responsible for negative differential resistance effects. PMID:26186139

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

    PubMed

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

    2013-10-01

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

  14. Trajectory-based solution of the nonadiabatic quantum dynamics equations: an on-the-fly approach for molecular dynamics simulations.

    PubMed

    Curchod, Basile F E; Tavernelli, Ivano; Rothlisberger, Ursula

    2011-02-28

    The non-relativistic quantum dynamics of nuclei and electrons is solved within the framework of quantum hydrodynamics using the adiabatic representation of the electronic states. An on-the-fly trajectory-based nonadiabatic molecular dynamics algorithm is derived, which is also able to capture nuclear quantum effects that are missing in the traditional trajectory surface hopping approach based on the independent trajectory approximation. The use of correlated trajectories produces quantum dynamics, which is in principle exact and computationally very efficient. The method is first tested on a series of model potentials and then applied to study the molecular collision of H with H(2) using on-the-fly TDDFT potential energy surfaces and nonadiabatic coupling vectors. PMID:21264437

  15. Molecular Corridor Based Approach for Description of Evolution of Secondary Organic Aerosols

    NASA Astrophysics Data System (ADS)

    Li, Y., Sr.; Poeschl, U.; Shiraiwa, M.

    2015-12-01

    Organic aerosol is ubiquitous in the atmosphere and its major component is secondary organic aerosol (SOA). Formation and evolution of SOA is a complex process involving coupled chemical reactions and mass transport in the gas and particle phases (Shiraiwa et al., 2014). Current air quality models do not embody the full spectrum of reaction and transport processes, nor do they identify the dominant rate-limiting steps in SOA formation, resulting in the significant underprediction of observed SOA concentrations, which precludes reliable quantitative predictions of aerosols and their environmental impacts. Recently, it has been suggested that the SOA chemical evolution can be represented well by "molecular corridor" with a tight inverse correlation between molar mass and volatility of SOA oxidation products (Shiraiwa et al., 2014). Here we further analyzed the structure, molar mass and volatility of 31,000 unique organic compounds. These compounds include oxygenated organic compounds as well as nitrogen- and sulfur-containing organics such as amines, organonitrates, and organosulfates. Results show that most of those compounds fall into this two-dimensional (2-D) space, which is constrained by two boundary lines corresponding to the volatility of n -alkanes CnH2n+2 and sugar alcohols CnH2n+2On. A method to predict the volatility of nitrogen- and sulfur- containing compounds is developed based on those 31,000 organic compounds. It is shown that the volatility can be well predicted as a function of chemical composition numbers, providing a way to apply this 2-D space to organic compounds observed in real atmosphere. A comprehensive set of observation data from laboratory experiments, field campaigns and indoor measurements is mapped to the molecular corridor. This 2-D space can successfully grasp the properties of organic compounds formed in different atmospheric conditions. The molecular corridor represents a new framework in which chemical and physical properties as

  16. Dealing with the Challenges of Teaching Molecular Biophysics to Biochemistry Majors through an Heuristics-Based Approach

    ERIC Educational Resources Information Center

    Castanho, Miguel A. R. B.

    2002-01-01

    The main distinction between the overlapping fields of molecular biophysics and biochemistry resides in their different approaches to the same problems. Molecular biophysics makes more use of physical techniques and focuses on quantitative data. This difference encounters two difficult pedagogical challenges when teaching molecular biophysics to…

  17. De novo design of drug-like molecules by a fragment-based molecular evolutionary approach.

    PubMed

    Kawai, Kentaro; Nagata, Naoya; Takahashi, Yoshimasa

    2014-01-27

    This paper describes a similarity-driven simple evolutionary approach to producing candidate molecules of new drugs. The aim of the method is to explore the candidates that are structurally similar to the reference molecule and yet somewhat different in not only peripheral chains but also their scaffolds. The method employs a known active molecule of our interest as a reference molecule which is used to navigate a huge chemical space. The reference molecule is also used to obtain seed fragments. An initial set of individual structures is prepared with the seed fragments and additional fragments using several connection rules. The fragment library is preferably prepared from a collection of known molecules related to the target of the reference molecule. Every fragment of the library can be used for fragment-based mutation. All the fragments are categorized into three classes; rings, linkers, and side chains. New individuals are produced by the crossover and the fragment-based mutation with the fragment library. Computer experiments with our own fragment library prepared from GPCR SARfari verified the feasibility of our approach to drug discovery. PMID:24372539

  18. Carbyne: The Molecular Approach.

    PubMed

    Tykwinski, Rik R

    2015-12-01

    For the last 60+ years, the synthesis and study of cumulenes and polyynes have been the focus of a small, but dedicated, group of researchers. Many of the remarkable electronic, optical, and structural properties of cumulenes and polyynes had already been identified in the earliest reports. The molecular lengths achievable by the initial syntheses were, unfortunately, somewhat limited by synthetic methods available. For the past 15 years, we have worked toward expanding on the synthesis of cumulenes and polyynes through the development of new methods and stabilization motifs. As new compounds have become available, homologous series of cumulenes and polyynes have then been examined as a function of molecular length. While we are not yet there, we would like to eventually provide a general description of the sp-carbon allotrope carbyne, and this account presents some of our efforts toward this goal. PMID:26200096

  19. Investigation of mechanical strength of 2D nanoscale structures using a molecular dynamics based computational intelligence approach

    NASA Astrophysics Data System (ADS)

    Garg, A.; Vijayaraghavan, V.; Wong, C. H.; Tai, K.; Singru, Pravin M.; Mahapatra, S. S.; Sangwan, K. S.

    2015-09-01

    A molecular dynamics (MD) based computational intelligence (CI) approach is proposed to investigate the Young modulus of two graphene sheets: Armchair and Zigzag. In this approach, the effect of aspect ratio, the temperature, the number of atomic planes and the vacancy defects on the Young modulus of two graphene sheets are first analyzed using the MD simulation. The data obtained using the MD simulation is then fed into the paradigm of a CI cluster comprising of genetic programming, which was specifically designed to formulate the explicit relationship of Young modulus of two graphene structures. We find that the MD-based-CI model is able to model the Young modulus of two graphene structures very well, which compiles in good agreement with that of experimental results obtained from the literature. Additionally, we also conducted sensitivity and parametric analysis and found that the number of defects has the most dominating influence on the Young modulus of two graphene structures.

  20. Applying molecular-based approaches to classical biological control of weeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Modern advances in molecular techniques are only recently being incorporated into programs for the classical biological control of weeds. Molecular analyses are able to elucidate information about target weeds that is critical to improving control success, such as taxonomic clarification, evidence o...

  1. Practicing Real Science in the Laboratory: A Project-Based Approach to Teaching Molecular Biology.

    ERIC Educational Resources Information Center

    Wimmers, Larry E.

    2001-01-01

    Describes a molecular biology laboratory in which students study the role of the enzyme polygalacturonase in the softening of tomatoes during ripening by developing their own hypotheses and designing their own experiments. (MM)

  2. Molecular Features Related to HIV Integrase Inhibition Obtained from Structure- and Ligand-Based Approaches

    PubMed Central

    de Carvalho, Luciana L.; Maltarollo, Vinícius G.; de Lima, Emmanuela Ferreira; Weber, Karen C.; Honorio, Kathia M.; da Silva, Albérico B. F.

    2014-01-01

    Among several biological targets to treat AIDS, HIV integrase is a promising enzyme that can be employed to develop new anti-HIV agents. The aim of this work is to propose a mechanistic interpretation of HIV-1 integrase inhibition and to rationalize the molecular features related to the binding affinity of studied ligands. A set of 79 HIV-1 integrase inhibitors and its relationship with biological activity are investigated employing 2D and 3D QSAR models, docking analysis and DFT studies. Analyses of docking poses and frontier molecular orbitals revealed important features on the main ligand-receptor interactions. 2D and 3D models presenting good internal consistency, predictive power and stability were obtained in all cases. Significant correlation coefficients (r2 = 0.908 and q2 = 0.643 for 2D model; r2 = 0.904 and q2 = 0.719 for 3D model) were obtained, indicating the potential of these models for untested compounds. The generated holograms and contribution maps revealed important molecular requirements to HIV-1 IN inhibition and several evidences for molecular modifications. The final models along with information resulting from molecular orbitals, 2D contribution and 3D contour maps should be useful in the design of new inhibitors with increased potency and selectivity within the chemical diversity of the data. PMID:24416129

  3. Molecular Approaches to Sarcoma Therapy

    PubMed Central

    Olsen, R. J.; Tarantolo, S. R.

    2002-01-01

    Soft tissue sarcomas comprise a heterogeneous group of aggressive tumors that have a relatively poor prognosis. Although conventional therapeutic regimens can effectively cytoreduce the overall tumor mass, they fail to consistently achieve a curative outcome. Alternative gene-based approaches that counteract the underlying neoplastic process by eliminating the clonal aberrations that potentiate malignant behavior have been proposed. As compared to the accumulation of gene alterations associated with epithelial carcinomas, sarcomas are frequently characterized by the unique presence of a single chromosomal translocation in each histological subtype. Similar to the Philadelphia chromosome associated with CML, these clonal abnormalities result in the fusion of two independent unrelated genes to generate a unique chimeric protein that displays aberrant activity believed to initiate cellular transformation. Secondary gene mutations may provide an additional growth advantage that further contributes to malignant progression. The recent clinical success of the tyrosine kinase inhibitor, STI571, suggests that therapeutic approaches specifically directed against essential survival factors in sarcoma cells may be effective. This review summarizes published approaches targeting a specific molecular mechanism associated with sarcomagenesis. The strategy and significance of published translational studies in six distinct areas are presented. These include: (1) the disruption of chimeric transcription factor activity; (2) inhibition of growth stimulatory post-translational modifications; (3) restoration of tumor suppressor function; (4) interference with angiogenesis; (5) induction of apoptotic pathways; and (6) introduction of toxic gene products. The potential for improving outcomes in sarcoma patients and the conceptual obstacles to be overcome are discussed. PMID:18521343

  4. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    NASA Astrophysics Data System (ADS)

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-05-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.

  5. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    PubMed Central

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-01-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted. PMID:27150583

  6. Bacterial diversity in a contaminated Alpine glacier as determined by culture-based and molecular approaches.

    PubMed

    Cappa, Fabrizio; Suciu, Nicoleta; Trevisan, Marco; Ferrari, Susanna; Puglisi, Edoardo; Cocconcelli, Pier Sandro

    2014-11-01

    Glaciers are important ecosystems, hosting bacterial communities that are adapted to cold conditions and scarcity of available nutrients. Several works focused on the composition of bacterial communities in glaciers and on the long-range atmospheric deposition of pollutants in glaciers, but it is not clear yet if ski resorts can represent a source of point pollution in near-by glaciers, and if these pollutants can influence the residing bacterial communities. To test these hypotheses, 12 samples were analyzed in Madaccio Glacier, in a 3200 ma.s.l. from two areas, one undisturbed and one close to a summer ski resort that is active since the 1930s. Chemical analyses found concentrations up to 43 ng L(-1) for PCBs and up to 168 μg L(-1) for PAHs in the contaminated area: these values are significantly higher than the ones found in undisturbed glaciers because of long-range atmospheric deposition events, and can be explained as being related to the near-by ski resort activities. Isolation of strains on rich medium plates and PCR-DGGE analyses followed by sequencing of bands allowed the identification of a bacterial community with phylogenetic patterns close to other glacier environments, with Proteobacteria and Actinobacteria the mostly abundant phyla, with Acidobacteria, Firmicutes and Cyanobacteria also represented in the culture-independent analyses. A number of isolates were identified by molecular and biochemical methods as phylogenetic related to known xenobiotic-degrading strains: glaciers subjected to chemical contamination can be important reservoirs of bacterial strains with potential applications in bioremediation. PMID:25117971

  7. Horizontal transfer of archaeal genes into the deinococcaceae: detection by molecular and computer-based approaches

    NASA Technical Reports Server (NTRS)

    Olendzenski, L.; Liu, L.; Zhaxybayeva, O.; Murphey, R.; Shin, D. G.; Gogarten, J. P.

    2000-01-01

    Members of the Deinococcaceae (e.g., Thermus, Meiothermus, Deinococcus) contain A/V-ATPases typically found in Archaea or Eukaryotes which were probably acquired by horizontal gene transfer. Two methods were used to quantify the extent to which archaeal or eukaryotic genes have been acquired by this lineage. Screening of a Meiothermus ruber library with probes made against Thermoplasma acidophilum DNA yielded a number of clones which hybridized more strongly than background. One of these contained the prolyl tRNA synthetase (RS) gene. Phylogenetic analysis shows the M. ruber and D. radiodurans prolyl RS to be more closely related to archaeal and eukaryal forms of this gene than to the typical bacterial type. Using a bioinformatics approach, putative open reading frames (ORFs) from the prerelease version of the D. radiodurans genome were screened for genes more closely related to archaeal or eukaryotic genes. Putative ORFs were searched against representative genomes from each of the three domains using automated BLAST. ORFs showing the highest matches against archaeal and eukaryotic genes were collected and ranked. Among the top-ranked hits were the A/V-ATPase catalytic and noncatalytic subunits and the prolyl RS genes. Using phylogenetic methods, ORFs were analyzed and trees assessed for evidence of horizontal gene transfer. Of the 45 genes examined, 20 showed topologies in which D. radiodurans homologues clearly group with eukaryotic or archaeal homologues, and 17 additional trees were found to show probable evidence of horizontal gene transfer. Compared to the total number of ORFs in the genome, those that can be identified as having been acquired from Archaea or Eukaryotes are relatively few (approximately 1%), suggesting that interdomain transfer is rare.

  8. Molecular-based approach to the differentiation of mealybug (Hemiptera: Pseudococcidae) species.

    PubMed

    Beuning, L L; Murphy, P; Wu, E; Batchelor, T A; Morris, B A

    1999-04-01

    The rDNA internal transcribed spacer (ITS) region of 4 mealybug species, Pseudococcus viburni (Signoret), P. longispinus (Targiono-Tozzetti), P. calceolariae (Maskell), and P. similans (Lidgett), was isolated by polymerase chain reaction (PCR) amplification, cloned, and sequenced. In this region of the genome there were numerous differences, including nucleotide substitutions, insertions, or deletions between P. viburni, P. longispinus, and P. calceolariae, whereas P. calceolariae and P. similans were very similar. Based on sequence differences between the ITS regions, we designed PCR primers that were able to differentiate the 4 mealybug species and that correlated with morphological differences found between adult females of these species. The PCR amplification by using the species-specific primers enabled the differentiation of not only adult females but also eggs, juveniles, and adult males, which was not previously possible by using conventional identification methods. PMID:10333754

  9. Small-molecule interferon inducers. Toward the comprehension of the molecular determinants through ligand-based approaches.

    PubMed

    Musmuca, Ira; Simeoni, Silvia; Caroli, Antonia; Ragno, Rino

    2009-07-01

    Hepatitis C is becoming an increasingly common cause of mortality especially in the HIV-coinfected group. Due to the efficacy of interferon (IFN) based therapy in the treatment of hepatitis C, various compounds possessing IFN-inducing activity have been hitherto reported. In the present study, we describe how steric, electrostatic, hydrophobic, and hydrogen-bonding interactions might influence the biological activity of a published set of IFN inducers, using a three-dimensional quantitative structure-activity relationship (3-D QSAR) approach. Analyses were conducted evaluating different series of compounds structurally related to 8-hydroxyadenines and 1H-imidazo[4,5-c]quinolines. A ligand-based alignment protocol in combination with the GRID/GOLPE approach was applied: 62 3-D QSAR models were derived using different GRID probes and several training sets. Performed 3-D QSAR investigations proved to be of good statistical value displaying r2, q2CV-LOO, and cross-validated SDEP values of 0.73, 0.61, 0.61 and 0.89, 0.64, 0.58 using the OH or the DRY probe, respectively. Additionally, the predictive performance was evaluated using an external test set of 20 compounds. Analyses of the resulting models led to the definition of a pharmacophore model that can be of interest to explain the observed affinities of known compounds as well as to design novel low molecular weight IFN inducers (IFNIs). To the best of our knowledge, this is the first 3-D QSAR application on IFN-inducing agents. PMID:19499914

  10. Molecular Approaches to Studying Denitrification

    NASA Astrophysics Data System (ADS)

    Voytek, M. A.

    2001-05-01

    Denitrification is carried out by a diverse array of microbes, mainly as an alternative mode of respiration that allows the organisms to respire using oxidized N compounds instead of oxygen. A common approach in biogeochemistry to the study of the regulation of denitrification is to assess activity by mass balance of substrates and products or direct rate measurements and has intrinsically assumed resource regulation of denitrification. Reported rates can vary significantly even among ecosystems characterized by similar environmental conditions, thus indicating that direct control by abiotic factors often is not sufficient to predict denitrification rates accurately in natural environments. Alternatively, a microbiological approach would proceed with the identification of the organisms responsible and an evaluation of the effect of environmental factors on the biochemical pathways involved. Traditional studies have relied on culturing techniques, such as most probable number enrichments, and have failed to assess the role of the predominately uncultivable members of the microbial community. A combination of biogeochemical measurements and the assessment of the microbial community is necessary and becoming increasingly possible with the development and application of molecular techniques. In order to understand how the composition and physiological behavior of the microbial community affects denitrification rates, we use a suite of molecular techniques developed for phylogenetic and metabolic characterization of denitrifying communities. Molecular tools available for quantifying denitrifying bacteria and assessing their diversity and activity are summarized. Their application is illustrated with examples from marine and freshwater environments. Emerging techniques and their application to ground water studies will be discussed.

  11. Molecular Approaches to Malaria 2000.

    PubMed

    Cowman, Alan F.; Cooke, Brian M.

    2000-04-01

    For more than 20 years now, Australia has been officially free of endemic malaria, but this devastating disease once again made a major impact on the continent in February 2000 when Melbourne hosted Australia's first major international conference on 'Molecular Approaches to Malaria' (Lorne, Australia, 2-5 February 2000). The global research effort toward our increased understanding of the pathogenesis and control of malaria in the post-genomics era was discussed and debated at length over 4 days packed with science encompassing molecular biology, cell biology, clinical studies, genomics, vaccines and pathogenic mechanisms. More than 260 researchers from 18 countries worldwide participated in this interdisciplinary meeting which comprised 57 oral presentations and 122 posters. Here we summarize some presentations pertinent to the field of drug action and resistance. Copyright 2000 Harcourt Publishers Ltd. PMID:11498369

  12. Molecular-based approaches to characterize coastal microbial community and their potential relation to the trophic state of Red Sea.

    PubMed

    Ansari, Mohd Ikram; Harb, Moustapha; Jones, Burton; Hong, Pei-Ying

    2015-01-01

    Molecular-based approaches were used to characterize the coastal microbiota and to elucidate the trophic state of Red Sea. Nutrient content and enterococci numbers were monitored, and used to correlate with the abundance of microbial markers. Microbial source tracking revealed the presence of >1 human-associated Bacteroides spp. at some of the near-shore sampling sites and at a heavily frequented beach. Water samples collected from the beaches had occasional exceedances in enterococci numbers, higher total organic carbon (TOC, 1.48-2.18 mg/L) and nitrogen (TN, 0.15-0.27 mg/L) than that detected in the near-shore waters. Enterococci abundances obtained from next-generation sequencing did not correlate well with the cultured enterococci numbers. The abundance of certain genera, for example Arcobacter, Pseudomonas and unclassified Campylobacterales, was observed to exhibit slight correlation with TOC and TN. Low abundance of functional genes accounting for up to 41 copies/L of each Pseudomonas aeruginosa and Campylobacter coli were detected. Arcobacter butzleri was also detected in abundance ranging from 111 to 238 copies/L. Operational taxonomic units (OTUs) associated with cyanobacteria, Prochlorococcus, Ostreococcus spp. and Gramella were more prevalent in waters that were likely impacted by urban runoffs and recreational activities. These OTUs could potentially serve as quantifiable markers indicative of the water quality. PMID:25758166

  13. Molecular-based approaches to characterize coastal microbial community and their potential relation to the trophic state of Red Sea

    PubMed Central

    Ansari, Mohd Ikram; Harb, Moustapha; Jones, Burton; Hong, Pei-Ying

    2015-01-01

    Molecular-based approaches were used to characterize the coastal microbiota and to elucidate the trophic state of Red Sea. Nutrient content and enterococci numbers were monitored, and used to correlate with the abundance of microbial markers. Microbial source tracking revealed the presence of >1 human-associated Bacteroides spp. at some of the near-shore sampling sites and at a heavily frequented beach. Water samples collected from the beaches had occasional exceedances in enterococci numbers, higher total organic carbon (TOC, 1.48–2.18 mg/L) and nitrogen (TN, 0.15–0.27 mg/L) than that detected in the near-shore waters. Enterococci abundances obtained from next-generation sequencing did not correlate well with the cultured enterococci numbers. The abundance of certain genera, for example Arcobacter, Pseudomonas and unclassified Campylobacterales, was observed to exhibit slight correlation with TOC and TN. Low abundance of functional genes accounting for up to 41 copies/L of each Pseudomonas aeruginosa and Campylobacter coli were detected. Arcobacter butzleri was also detected in abundance ranging from 111 to 238 copies/L. Operational taxonomic units (OTUs) associated with cyanobacteria, Prochlorococcus, Ostreococcus spp. and Gramella were more prevalent in waters that were likely impacted by urban runoffs and recreational activities. These OTUs could potentially serve as quantifiable markers indicative of the water quality. PMID:25758166

  14. A Modular, Energy-Based Approach to the Development of Nickel Containing Molecular Electrocatalysts for Hydrogen Production and Oxidation

    SciTech Connect

    Shaw, Wendy J.; Helm, Monte L.; DuBois, Daniel L.

    2013-08-01

    This review discusses the development of molecular electrocatalysts for H2 production and oxidation based on nickel. A modular approach is used in which the structure of the catalyst is divided into first second and outer coordination spheres. The first coordination sphere consists of the ligands bound directly to the metal center, and this coordination sphere can be used to control such factors as the presence or absence of vacant coordination sites, redox potentials, hydride acceptor abilities and other important thermodynamic parameters. The second coordination sphere is defined as functional groups such as pendant acids or bases that can interact with bound substrates such as H2 molecules and hydride ligands, but that do not form strong bonds with the metal center. These functional groups can play diverse roles such as assisting the heterolytic cleavage of H2, controlling intra- and intermolecular proton transfer reactions, and provide a physical pathway for coupling proton and electron transfer reactions. By controlling both the hydride donor/acceptor ability of the catalysts using the first coordination sphere and the proton acceptor/donor abilities of the functional groups in the second coordination sphere, catalysts can be designed that are biased toward H2 production, H2 oxidation, or that are bidirectional (catalyzing both H2 oxidation and production). The outer coordination sphere is defined as that portion of the catalytic system that are not in the first and second coordination spheres. This coordination sphere can assist in the delivery of protons and electrons to and from the catalytically active site, thereby adding another important avenue for controlling catalytic activity. Many features of these simple catalytic systems are good models for enzymes and they provide the opportunity to probe certain aspects of catalysis that may be difficult in enzymes themselves, but that can provide insights into enzyme function and reactivity.

  15. Molecular approaches to Taenia asiatica.

    PubMed

    Jeon, Hyeong-Kyu; Eom, Keeseon S

    2013-02-01

    Taenia solium, T. saginata, and T. asiatica are taeniid tapeworms that cause taeniasis in humans and cysticercosis in intermediate host animals. Taeniases remain an important public health concerns in the world. Molecular diagnostic methods using PCR assays have been developed for rapid and accurate detection of human infecting taeniid tapeworms, including the use of sequence-specific DNA probes, PCR-RFLP, and multiplex PCR. More recently, DNA diagnosis using PCR based on histopathological specimens such as 10% formalin-fixed paraffin-embedded and stained sections mounted on slides has been applied to cestode infections. The mitochondrial gene sequence is believed to be a very useful molecular marker for not only studying evolutionary relationships among distantly related taxa, but also for investigating the phylo-biogeography of closely related species. The complete sequence of the human Taenia tapeworms mitochondrial genomes were determined, and its organization and structure were compared to other human-tropic Taenia tapeworms for which complete mitochondrial sequence data were available. The multiplex PCR assay with the Ta4978F, Ts5058F, Tso7421F, and Rev7915 primers will be useful for differential diagnosis, molecular characterization, and epidemiological surveys of human Taenia tapeworms. PMID:23467738

  16. Quantitative and qualitative validations of a sonication-based DNA extraction approach for PCR-based molecular biological analyses.

    PubMed

    Dai, Xiaohu; Chen, Sisi; Li, Ning; Yan, Han

    2016-05-15

    The aim of this study was to comprehensively validate the sonication-based DNA extraction method, in hope of the replacement of the so-called 'standard DNA extraction method' - the commercial kit method. Microbial cells in the digested sludge sample, containing relatively high amount of PCR-inhibitory substances, such as humic acid and protein, were applied as the experimental alternatives. The procedure involving solid/liquid separation of sludge sample and dilution of both DNA templates and inhibitors, the minimum templates for PCR-based analyses, and the in-depth understanding from the bias analysis by pyrosequencing technology were obtained and confirmed the availability of the sonication-based DNA extraction method. PMID:26774955

  17. New approaches to molecular diagnosis.

    PubMed

    Korf, Bruce R; Rehm, Heidi L

    2013-04-10

    Advances in understanding the molecular basis of rare and common disorders, as well as in the technology of DNA analysis, are rapidly changing the landscape of molecular genetic and genomic testing. High-resolution molecular cytogenetic analysis can now detect deletions or duplications of DNA of a few hundred thousand nucleotides, well below the resolution of the light microscope. Diagnostic testing for "single-gene" disorders can be done by targeted analysis for specific mutations, by sequencing a specific gene to scan for mutations, or by analyzing multiple genes in which mutation may lead to a similar phenotype. The advent of massively parallel next-generation sequencing facilitates the analysis of multiple genes and now is being used to sequence the coding regions of the genome (the exome) for clinical testing. Exome sequencing requires bioinformatic analysis of the thousands of variants that are identified to find one that is contributing to the pathology; there is also a possibility of incidental identification of other medically significant variants, which may complicate genetic counseling. DNA testing can also be used to identify variants that influence drug metabolism or interaction of a drug with its cellular target, allowing customization of choice of drug and dosage. Exome and genome sequencing are being applied to identify specific gene changes in cancer cells to guide therapy, to identify inherited cancer risk, and to estimate prognosis. Genomic testing may be used to identify risk factors for common disorders, although the clinical utility of such testing is unclear. Genetic and genomic tests may raise new ethical, legal, and social issues, some of which may be addressed by existing genetic nondiscrimination legislation, but which also must be addressed in the course of genetic counseling. The purpose of this article is to assist physicians in recognizing where new approaches to genetic and genomic testing may be applied clinically and in being aware

  18. Approaches towards molecular amplification for sensing.

    PubMed

    Goggins, Sean; Frost, Christopher G

    2016-06-01

    Diagnostic assays that rely on molecular interactions have come a long way; from initial reversible detection systems towards irreversible reaction indicator-based methods. More recently, the emergence of innovative molecular amplification methodologies has revolutionised sensing, allowing diagnostic assays to achieve ultra-low limits of detection. There have been a significant number of molecular amplification approaches developed over recent years to accommodate the wide variety of analytes that require sensitive detection. To celebrate this achievement, this comprehensive critical review has been compiled to give a broad overview of the many different approaches used to attain amplification in sensing with an aim to inspire the next generation of diagnostic assays looking to achieve the ultimate detection limit. This review has been created with the focus on how each conceptually unique molecular amplification methodology achieves amplification, not just its sensitivity, while highlighting any key processes. Excluded are any references that were not found to contain an obvious molecular amplifier or amplification component, or that did not use an appropriate signal readout that could be incorporated into a sensing application. Additionally, methodologies where amplification is achieved through advances in instrumentation are also excluded. Depending upon the type of approach employed, amplification strategies are divided into four categories: target, label, signal or receptor amplification. More recent, more complex protocols combine a number of approaches and are therefore categorised by which amplification component described within was considered as the biggest advancement. The advantages and disadvantages of each methodology are discussed along with any limits of detection, if stated in the original article. Any subsequent use of the methodology within sensing or any other application is also mentioned to draw attention to its practicality. The importance of

  19. A Self-Instructional Approach To the Teaching of Enzymology Involving Computer-Based Sequence Analysis and Molecular Modelling.

    ERIC Educational Resources Information Center

    Attwood, Paul V.

    1997-01-01

    Describes a self-instructional assignment approach to the teaching of advanced enzymology. Presents an assignment that offers a means of teaching enzymology to students that exposes them to modern computer-based techniques of analyzing protein structure and relates structure to enzyme function. (JRH)

  20. Modulation of electronic and self-assembly properties of a donor-acceptor-donor-based molecular materials via atomistic approach.

    PubMed

    Dhar, Joydeep; Swathi, K; Karothu, Durga Prasad; Narayan, K S; Patil, Satish

    2015-01-14

    The performance of molecular materials in optoelectronic devices critically depends upon their electronic properties and solid-state structure. In this report, we have synthesized sulfur and selenium based (T4BT and T4BSe) donor-acceptor-donor (D-A-D) organic derivatives in order to understand the structure-property correlation in organic semiconductors by selectively tuning the chalcogen atom. The photophysical properties exhibit a significant alteration upon varying a single atom in the molecular structure. A joint theoretical and experimental investigation suggests that replacing sulfur with selenium significantly reduces the band gap and molar absorption coefficient because of lower electronegativity and ionization potential of selenium. Single-crystal X-ray diffraction analysis showed differences in their solid-state packing and intermolecular interactions. Subsequently, difference in the solid-state packing results variation in self-assembly. Micorstructural changes within these materials are correlated to their electrical resistance variation, investigated by conducting probe atomic force microscopy (CP-AFM) measurements. These results provide useful guidelines to understand the fundamental properties of D-A-D materials prepared by atomistic modulation. PMID:25532139

  1. A molecular-based approach for examining responses of eukaryotes in microcosms to contaminant-spiked estuarine sediments.

    PubMed

    Chariton, Anthony A; Ho, Kay T; Proestou, Dina; Bik, Holly; Simpson, Stuart L; Portis, Lisa M; Cantwell, Mark G; Baguley, Jeffrey G; Burgess, Robert M; Pelletier, Marguerite M; Perron, Monique; Gunsch, Claudia; Matthews, Robin A

    2014-02-01

    Ecotoxicological information for most contaminants is limited to a small number of taxa, and these are generally restricted to comparatively hardy organisms that are readily extractable from test media and easily identifiable. Advances in DNA sequencing can now provide a comprehensive view of benthic invertebrate diversity. The authors applied 454 pyrosequencing to examine the responses of benthic communities in microcosms exposed to sediments with elevated concentrations of triclosan, the endpoint being eukaryl communities that have successfully vertically migrated through the manipulated sediments. The biological communities associated with the 3 treatments (control triclosan, low triclosan [14 mg/kg], and high triclosan [180 mg/kg]) clustered into 3 groups: control/low (n = 6 controls and 4 low), moderate (n = 2 low), and high (n = 5 high). One sample was discarded as an outlier. The most pronounced change as a response to triclosan was the loss of number of metazoan operational taxonomic units (OTUs), indicative of the control/low and moderate groups, with this being most evident in the range of taxa associated with the classes Chromadorea and Bivalvia and the phylum Kinorhyncha. The authors also describe a range of other taxa that aided discrimination between the groups; compare findings with traditionally obtained meio- and macrofaunal communities obtained from the same experiment; and illustrate some of the advantages and limitations associated with both the molecular and traditional approaches. The described approach illustrates the capacity for amplicon sequencing to provide ecologically relevant information that can be used to strengthen an understanding of how sedimentary communities respond to a range of environmental stressors. PMID:24399368

  2. Insights into the inhibition and mechanism of compounds against LPS-induced PGE2 production: a pathway network-based approach and molecular dynamics simulations.

    PubMed

    Zhang, Xinzhuang; Gu, Jiangyong; Cao, Liang; Ma, Yimin; Su, Zhenzhen; Luo, Fang; Wang, Zhenzhong; Li, Na; Yuan, Gu; Chen, Lirong; Xu, Xiaojie; Xiao, Wei

    2014-12-01

    In comparison to the current target-based screening approach, it is increasingly evident that active lead compounds based on disease-related phenotypes are more likely to be translated to clinical trials during drug development. That is, because human diseases are in essence the outcome of the abnormal function of multiple genes, especially in complex diseases. Therefore, as a conventional technology in the early phase of active lead compound discovery, computational methods that can connect molecular interactions and disease-related phenotypes to evaluate the efficacy of compounds are in urgently required. In this work, a computational approach that integrates molecular docking and pathway network analysis (network efficiency and network flux) was developed to evaluate the efficacy of a compound against LPS-induced Prostaglandin E2(PGE2) production. The predicted results were then validated in vitro, and a correlation with the experimental results was analyzed using linear regression. In addition, molecular dynamics (MD) simulations were performed to explore the molecular mechanism of the most potent compounds. There were 12 hits out of 28 predicted ingredients separated from Reduning injection (RDN). The predicted results have a good agreement with the experimental inhibitory potency (IC50) (correlation coefficient = 0.80). The most potent compounds could target several proteins to regulate the pathway network. This might partly interpret the molecular mechanism of RDN on fever. Meanwhile, the good correlation of the computational model with the wet experimental results might bridge the gap between molecule-target interactions and phenotypic response, especially for multi-target compounds. Therefore, it would be helpful for active lead compound discovery, the understanding of the multiple targets and synergic essence of traditional Chinese medicine (TCM). PMID:25228393

  3. Ab initio molecular orbital-configuration interaction based quantum master equation (MOQME) approach to the dynamic first hyperpolarizabilities of asymmetric π-conjugated systems

    SciTech Connect

    Kishi, Ryohei; Fujii, Hiroaki; Minami, Takuya; Shigeta, Yasuteru; Nakano, Masayoshi

    2015-01-22

    In this study, we apply the ab initio molecular orbital - configuration interaction based quantum master equation (MOQME) approach to the calculation and analysis of the dynamic first hyperpolarizabilities (β) of asymmetric π-conjugated molecules. In this approach, we construct the excited state models by the ab initio configuration interaction singles method. Then, time evolutions of system reduced density matrix ρ(t) and system polarization p(t) are calculated by the QME approach. Dynamic β in the second harmonic generation is calculated based on the nonperturbative definition of nonlinear optical susceptibility, using the frequency domain system polarization p(ω). Spatial contributions of electrons to β are analyzed based on the dynamic hyperpolarizability density map, which visualizes the second-order response of charge density oscillating with a frequency of 2ω. We apply the present method to the calculation of the dynamic β of a series of donor/acceptor substituted polyene oligomers, and then discuss the applicability of the MOQME method to the calculation and analysis of dynamic NLO properties of molecular systems.

  4. Molecular genetic approaches to understanding disease.

    PubMed Central

    Savill, J.

    1997-01-01

    Molecular genetics has greatly increased the understanding of diseases in which there is a single gene defect such as cystic fibrosis. Discovering the gene responsible and its function not only helps determine the pathogenesis of the disease but also offers a possible treatment-gene therapy. Polygenic disorders such as diabetes may soon yield their secrets to the same approach. Animal models of genetic diseases are proving useful research tools, and transgenesis has made xenografting possible. Furthermore, antisense technology allows specific inhibition of undesirably overexpressed genes such as those driving unwanted vascular cell proliferation and restenosis after angioplasty. The completion of the human genome project should make the search for "disease" gene much quicker and will increase still further the importance of these gene based approaches toward diseases. PMID:9006475

  5. Using Informatics-, Bioinformatics- and Genomics-Based Approaches for the Molecular Surveillance and Detection of Biothreat Agents

    NASA Astrophysics Data System (ADS)

    Seto, Donald

    The convergence and wealth of informatics, bioinformatics and genomics methods and associated resources allow a comprehensive and rapid approach for the surveillance and detection of bacterial and viral organisms. Coupled with the continuing race for the fastest, most cost-efficient and highest-quality DNA sequencing technology, that is, "next generation sequencing", the detection of biological threat agents by `cheaper and faster' means is possible. With the application of improved bioinformatic tools for the understanding of these genomes and for parsing unique pathogen genome signatures, along with `state-of-the-art' informatics which include faster computational methods, equipment and databases, it is feasible to apply new algorithms to biothreat agent detection. Two such methods are high-throughput DNA sequencing-based and resequencing microarray-based identification. These are illustrated and validated by two examples involving human adenoviruses, both from real-world test beds.

  6. Molecular Proxy Approaches for Paleohydrology

    NASA Astrophysics Data System (ADS)

    Freeman, K. H.; Smith, F. A.; Polissar, P.; Turich, C. H.; Pedentchouk, N.

    2004-12-01

    There is a rich assembly of isotopic and mineral indicators for paleohydrologic properties of ancient environments. Commonly employed examples include mineral abundance ratios and the isotopic signatures of minerals and macromolecular organic phases such as cellulose. Preservation of these materials can be influenced strongly by natural processes in the environment, most notably resulting in the alteration or loss of carbonate mineral isotopic signatures. In order to expand our ability to document paleoclimatic conditions in continental environments, additional tools for both aquatic and terrestrial settings are in development based on the hydrogen isotopic signatures of individual lipids from microbes, algae and vascular plants. Plant leaf waxes (long-chain n-alkanes) preserve well in soils and aquatic sediments. Deuterium signatures in ancient leaf lipids potentially record isotopic properties of ancient plant water, reflecting isotopic signatures of rainfall and soil waters as well as the level of relative humidity. We have studied grasses, trees and other plant types from both greenhouse and field localities in order to understand the relative influences of plant physiology, physiognomy,and growth conditions (humidity) on lipids as recorders of plant water isotopic signatures. Submerged aquatic algae are not directly influenced by humidity, and recent work has shown their biomarkers to be promising paleolimnological proxies. We will discuss the potential for algal compounds as recorders of waters in modern high altitude sites and for ancient paleoaltimetry applications. Recent theoretical considerations in conjunction with analyses of lipids from ancient sediments point to the limitation of the preservation of paleohydrologic signatures set by thermal maturation approaching oil-generating conditions.

  7. Multi-Server Approach for High-Throughput Molecular Descriptors Calculation based on Multi-Linear Algebraic Maps.

    PubMed

    García-Jacas, César R; Aguilera-Mendoza, Longendri; González-Pérez, Reisel; Marrero-Ponce, Yovani; Acevedo-Martínez, Liesner; Barigye, Stephen J; Avdeenko, Tatiana

    2015-01-01

    The present report introduces a novel module of the QuBiLS-MIDAS software for the distributed computation of the 3D Multi-Linear algebraic molecular indices. The main motivation for developing this module is to deal with the computational complexity experienced during the calculation of the descriptors over large datasets. To accomplish this task, a multi-server computing platform named T-arenal was developed, which is suited for institutions with many workstations interconnected through a local network and without resources particularly destined for computation tasks. This new system was deployed in 337 workstations and it was perfectly integrated with the QuBiLS-MIDAS software. To illustrate the usability of the T-arenal platform, performance tests over a dataset comprised of 15 000 compounds are carried out, yielding a 52 and 60 fold reduction in the sequential processing time for the 2-Linear and 3-Linear indices, respectively. Therefore, it can be stated that the T-arenal based distribution of computation tasks constitutes a suitable strategy for performing high-throughput calculations of 3D Multi-Linear descriptors over thousands of chemical structures for posterior QSAR and/or ADME-Tox studies. PMID:27490863

  8. Prepare, Do, Review: A skills-based approach for laboratory practical classes in biochemistry and molecular biology.

    PubMed

    Arthur, Peter; Ludwig, Martha; Castelli, Joane; Kirkwood, Paul; Attwood, Paul

    2016-05-01

    A new laboratory practical system is described which is comprised of a number of laboratory practical modules, each based around a particular technique or set of techniques, related to the theory part of the course but not designed to be dependent on it. Each module comprises an online recorded pre-lab lecture, the laboratory practical itself and a post-lab session in which students make oral presentations on different aspects of the practical. Each part of the module is assessed with the aim of providing rapid feedback to staff and students. Each laboratory practical is the responsibility of a single staff member and through this "ownership," continual review and updating is promoted. Examples of changes made by staff to modules as a result of student feedback are detailed. A survey of students who had experienced both the old-style laboratory course and the new one provided evidence of increased satisfaction with the new program. The assessment of acquired shills in the new program showed that it was much more effective than the old course. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:276-287, 2016. PMID:27161811

  9. Identification of dengue viral RNA-dependent RNA polymerase inhibitor using computational fragment-based approaches and molecular dynamics study.

    PubMed

    Anusuya, Shanmugam; Velmurugan, Devadasan; Gromiha, M Michael

    2016-07-01

    Dengue is a major public health concern in tropical and subtropical countries of the world. There are no specific drugs available to treat dengue. Even though several candidates targeted both viral and host proteins to overcome dengue infection, they have not yet entered into the later stages of clinical trials. In order to design a drug for dengue fever, newly emerged fragment-based drug designing technique was applied. RNA-dependent RNA polymerase, which is essential for dengue viral replication is chosen as a drug target for dengue drug discovery. A cascade of methods, fragment screening, fragment growing, and fragment linking revealed the compound [2-(4-carbamoylpiperidin-1-yl)-2-oxoethyl]8-(1,3-benzothiazol-2-yl)naphthalene-1-carboxylate as a potent dengue viral polymerase inhibitor. Both strain energy and binding free energy calculations predicted that this could be a better inhibitor than the existing ones. Molecular dynamics simulation studies showed that the dengue polymerase-lead complex is stable and their interactions are consistent throughout the simulation. The hydrogen-bonded interactions formed by the residues Arg792, Thr794, Ser796, and Asn405 are the primary contributors for the stability and the rigidity of the polymerase-lead complex. This might keep the polymerase in closed conformation and thus inhibits viral replication. Hence, this might be a promising lead molecule for dengue drug designing. Further optimization of this lead molecule would result in a potent drug for dengue. PMID:26262439

  10. Electrochemical sensor based on molecularly imprinted polymer for sensitive and selective determination of metronidazole via two different approaches.

    PubMed

    Liu, Jie; Tang, Hui; Zhang, Bo; Deng, Xiling; Zhao, Feilang; Zuo, Peng; Ye, Bang-Ce; Li, Yingchun

    2016-06-01

    A molecularly imprinted polymer decorated glassy carbon electrode (MIP/GCE) is facilely developed into an electrochemical sensing platform for detection of metronidazole (MNZ). MIP preparation was carried out via in situ electropolymerization and o-phenylenediamine was selected as the optimal functional monomer. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were employed to characterize and assess the performance of the so-obtained sensor. In particular, two assay methods, which are based on different principles, were involved in the detection procedure. One is based on MIP/catalysis (Method І) and the other is MIP/gate effect (Method II). Comparison of these two methods was made in the aspects including detection range, sensitivity, accuracy, selectivity, repeatability, and long-term stability. It is found that Method І affords a lower detection limit of 3.33 × 10(-10) M (S/N = 3) while the detection limit of Method II is 6.67 × 10(-10) M (S/N = 3). The linear range of Method І and II is 1.0 × 10(-9) to 1.0 × 10(-8) M and 2.0 × 10(-9) to 1.0 × 10(-7) M, respectively. The MIP/GCE exhibits good recognition ability towards the template molecule-MNZ in the presence of the analogues of MNZ and other interferents, which can be ascribed to the successful imprinting effect during MIP membrane preparation. Graphical Abstract Procedure for fabricating MIP/GCE and its application in detecting metronidazole in serum. PMID:27100231

  11. Dictyostelium discoideum: Molecular approaches to cell biology

    SciTech Connect

    Spudich, J.A.

    1987-01-01

    The central point of this book is to present Dictyostelium as a valuable eukaryotic organism for those interested in molecular studies that require a combined biochemical, structural, and genetic approach. The book is not meant to be a comprehensive compilation of all methods involving Dictyostelium, but instead is a selective set of chapters that demonstrates the utility of the organism for molecular approaches to interesting cell biological problems.

  12. Huntington Disease: Molecular Diagnostics Approach.

    PubMed

    Bastepe, Murat; Xin, Winnie

    2015-01-01

    Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at-risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed. PMID:26439718

  13. Characterization of the low-molecular-weight glutenin subunit gene family members using a PCR-based marker approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low-molecular-weight glutenin subunits (LMW-GS) are a class of seed storage proteins that play a major role in the determination of the processing quality of wheat flour. The LMW-GS are encoded by multi-gene families located on the short arms of the homoeologous group 1 chromosomes, at the Glu-A3, G...

  14. Using a Molecular-Genetic Approach to Investigate Bacterial Physiology in a Continuous, Research-Based, Semester-Long Laboratory for Undergraduates †

    PubMed Central

    Ault, Jeremiah Foster; Renfro, Betsey Marie; White, Andrea Kirsten

    2011-01-01

    Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigiosin pigment mutants in the bacterium, Serratia marcescens. This is followed by phenotypic characterization, cloning, and sequencing the Tn insertion site to identify genes involved in pigment biosynthesis. During this lab, students gain ample experience performing basic lab techniques while learning about — and applying — methods for elucidating gene function. The approach to the laboratory and the outcomes are intimately integrated into the teaching of many fundamental physiological processes underlying prodigiosin production in bacteria. The result is a cohesive course that integrates the theory and application of molecular genetic techniques with the study of bacterial physiology. Assessments of student learning objectives demonstrated that students greatly improved their understanding of both physiological processes and the genetic techniques used to investigate them. In addition, students felt that this semester-long exercise provided the necessary laboratory experience they needed and desired in preparation for careers in molecular biology, microbiology, and biochemistry. PMID:23653763

  15. Using a molecular-genetic approach to investigate bacterial physiology in a continuous, research-based, semester-long laboratory for undergraduates.

    PubMed

    Ault, Jeremiah Foster; Renfro, Betsey Marie; White, Andrea Kirsten

    2011-01-01

    Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigiosin pigment mutants in the bacterium, Serratia marcescens. This is followed by phenotypic characterization, cloning, and sequencing the Tn insertion site to identify genes involved in pigment biosynthesis. During this lab, students gain ample experience performing basic lab techniques while learning about - and applying - methods for elucidating gene function. The approach to the laboratory and the outcomes are intimately integrated into the teaching of many fundamental physiological processes underlying prodigiosin production in bacteria. The result is a cohesive course that integrates the theory and application of molecular genetic techniques with the study of bacterial physiology. Assessments of student learning objectives demonstrated that students greatly improved their understanding of both physiological processes and the genetic techniques used to investigate them. In addition, students felt that this semester-long exercise provided the necessary laboratory experience they needed and desired in preparation for careers in molecular biology, microbiology, and biochemistry. PMID:23653763

  16. Molecular Imaging of Myocardial Injury: A Magnetofluorescent Approach

    PubMed Central

    Sosnovik, David E.

    2009-01-01

    The role of molecular imaging in enhancing the understanding of myocardial injury and repair is rapidly expanding. Moreover, in recent years magnetic resonance and fluorescence-based approaches have been added to the molecular imaging armamentarium and have been used to image selected molecular and cellular targets in the myocardium. Apoptosis, necrosis, macrophage infiltration, myeloperoxidase activity, cathepsin activity, and type 1 collagen have all been imaged in vivo with a magnetofluorescent (MRI and/or fluorescence) approach. This review highlights the potential of these and other magnetofluorescent agents, with particular focus on their role in ischemic heart disease. PMID:20090858

  17. Configurational entropy of protein: A combined approach based on molecular simulation and integral-equation theory of liquids

    NASA Astrophysics Data System (ADS)

    Chong, Song-Ho; Ham, Sihyun

    2011-03-01

    We report the recent development of a theoretical method to calculate the protein configurational entropy in explicit solvent from statistical properties of the solvent-averaged protein potential energy surface. This method can be implemented by combining molecular simulation and integral-equation theory of liquids. Our method does not assume Gaussian distribution of protein configurations, and can be applied to unfolded or misfolded states of protein in which an average protein structure is not well defined. An illustrative application is made to misfolded state of 42-residue amyloid beta protein in water.

  18. Effect of water on the thermo-physical properties of Reline: An experimental and molecular simulation based approach.

    PubMed

    Shah, Dhawal; Mjalli, Farouq S

    2014-11-21

    Increasing applications of ionic liquids and their analogues, namely Deep Eutectic Solvents (DESs), requires further investigation into the effect of moisture content on the physico-chemical characteristics of these fluids. Although it is common practice to synthesize these fluids in a moisture-controlled environment, as moisture is generally considered to have an impact on their properties, there are no systematic studies on this. We herein examine the effects of water on Reline, a Type-III DES composed of urea and choline chloride. Experiments were performed to obtain the physical properties of aqueous Reline solution. We observed moderate changes in density, speed of sound, refractive index, and pH with increasing water fraction; however, the change in viscosity and conductivity was strong and exponential. In addition, molecular dynamics simulations were performed to analyze the intermolecular interactions of Reline and aqueous Reline solutions. The simulations primarily present the significance of urea-anion interaction to explain the low melting point of the DES. In the presence of water, the anion is preferentially hydrated as compared to urea or the cation. More interestingly, simulations help to classify the effects of water into different regimes. At low water fractions (<5%) the urea-urea interactions are enhanced, as is revealed through the hydrogen bond analysis. Beyond 25% water fractions, the components of Reline are individually hydrated and have high diffusivity, which is further reflected in the change in transport properties. The results presented herein provide valuable information on aqueous Reline solutions both in terms of experimental data and molecular insights, which in turn, we believe, might assist in developing further applications of Reline and other related DESs. PMID:25277220

  19. Development of 3D-QSAR Model for Acetylcholinesterase Inhibitors Using a Combination of Fingerprint, Molecular Docking, and Structure-Based Pharmacophore Approaches.

    PubMed

    Lee, Sehan; Barron, Mace G

    2015-11-01

    Acetylcholinesterase (AChE), a serine hydrolase vital for regulating the neurotransmitter acetylcholine in animals, has been used as a target for drugs and pesticides. With the increasing availability of AChE crystal structures, with or without ligands bound, structure-based approaches have been successfully applied to AChE inhibitors (AChEIs). The major limitation of these approaches has been the small applicability domain due to the lack of structural diversity in the training set. In this study, we developed a 3 dimensional quantitative structure-activity relationship (3D-QSAR) for inhibitory activity of 89 reversible and irreversible AChEIs including drugs and insecticides. A 3D-fingerprint descriptor encoding protein-ligand interactions was developed using molecular docking and structure-based pharmacophore to rationalize the structural requirements responsible for the activity of these compounds. The obtained 3D-QSAR model exhibited high correlation value (R(2) = 0.93) and low mean absolute error (MAE = 0.32 log units) for the training set (n = 63). The model was predictive across a range of structures as shown by the leave-one-out cross-validated correlation coefficient (Q(2) = 0.89) and external validation results (n = 26, R(2) = 0.89, and MAE = 0.38 log units). The model revealed that the compounds with high inhibition potency had proper conformation in the active site gorge and interacted with key amino acid residues, in particular Trp84 and Phe330 at the catalytic anionic site, Trp279 at the peripheral anionic site, and Gly118, Gly119, and Ala201 at the oxyanion hole. The resulting universal 3D-QSAR model provides insight into the multiple molecular interactions determining AChEI potency that may guide future chemical design and regulation of toxic AChEIs. PMID:26202430

  20. Low energy isomers of (H2O)25 from a hierarchical method based on Monte Carlo temperature basin paving and molecular tailoring approaches benchmarked by MP2 calculations

    NASA Astrophysics Data System (ADS)

    Sahu, Nityananda; Gadre, Shridhar R.; Rakshit, Avijit; Bandyopadhyay, Pradipta; Miliordos, Evangelos; Xantheas, Sotiris S.

    2014-10-01

    We report new global minimum candidate structures for the (H2O)25 cluster that are lower in energy than the ones reported previously and correspond to hydrogen bonded networks with 42 hydrogen bonds and an interior, fully coordinated water molecule. These were obtained as a result of a hierarchical approach based on initial Monte Carlo Temperature Basin Paving sampling of the cluster's Potential Energy Surface with the Effective Fragment Potential, subsequent geometry optimization using the Molecular Tailoring Approach with the fragments treated at the second order Møller-Plesset (MP2) perturbation (MTA-MP2) and final refinement of the entire cluster at the MP2 level of theory. The MTA-MP2 optimized cluster geometries, constructed from the fragments, were found to be within <0.5 kcal/mol from the minimum geometries obtained from the MP2 optimization of the entire (H2O)25 cluster. In addition, the grafting of the MTA-MP2 energies yields electronic energies that are within <0.3 kcal/mol from the MP2 energies of the entire cluster while preserving their energy rank order. Finally, the MTA-MP2 approach was found to reproduce the MP2 harmonic vibrational frequencies, constructed from the fragments, quite accurately when compared to the MP2 ones of the entire cluster in both the HOH bending and the OH stretching regions of the spectra.

  1. FRET-based Molecular Tension Microscopy.

    PubMed

    Gayrard, Charlène; Borghi, Nicolas

    2016-02-01

    Cells generate and experience mechanical forces that may shape tissues and regulate signaling pathways in a variety of physiological or pathological situations. How forces propagate and transduce signals at the molecular level is poorly understood. The advent of FRET-based Molecular Tension Microscopy now allows to achieve mechanical force measurements at a molecular scale with molecular specificity in situ, and thereby better understand the mechanical architecture of cells and tissues, and mechanotransduction pathways. In this review, we will first expose the basic principles of FRET-based MTM and its various incarnations. We will describe different ways of measuring FRET, their advantages and drawbacks. Then, throughout the range of proteins of interest, cells and organisms to which it has been applied, we will review the tests developed to validate the approach, how molecular tension was related to cell functions, and conclude with possible developments and offshoots. PMID:26210398

  2. Prepare, Do, Review: A Skills-Based Approach for Laboratory Practical Classes in Biochemistry and Molecular Biology

    ERIC Educational Resources Information Center

    Arthur, Peter; Ludwig, Martha; Castelli, Joane; Kirkwood, Paul; Attwood, Paul

    2016-01-01

    A new laboratory practical system is described which is comprised of a number of laboratory practical modules, each based around a particular technique or set of techniques, related to the theory part of the course but not designed to be dependent on it. Each module comprises an online recorded pre-lab lecture, the laboratory practical itself and…

  3. Polymer Fluid Dynamics: Continuum and Molecular Approaches.

    PubMed

    Bird, R B; Giacomin, A J

    2016-06-01

    To solve problems in polymer fluid dynamics, one needs the equations of continuity, motion, and energy. The last two equations contain the stress tensor and the heat-flux vector for the material. There are two ways to formulate the stress tensor: (a) One can write a continuum expression for the stress tensor in terms of kinematic tensors, or (b) one can select a molecular model that represents the polymer molecule and then develop an expression for the stress tensor from kinetic theory. The advantage of the kinetic theory approach is that one gets information about the relation between the molecular structure of the polymers and the rheological properties. We restrict the discussion primarily to the simplest stress tensor expressions or constitutive equations containing from two to four adjustable parameters, although we do indicate how these formulations may be extended to give more complicated expressions. We also explore how these simplest expressions are recovered as special cases of a more general framework, the Oldroyd 8-constant model. Studying the simplest models allows us to discover which types of empiricisms or molecular models seem to be worth investigating further. We also explore equivalences between continuum and molecular approaches. We restrict the discussion to several types of simple flows, such as shearing flows and extensional flows, which are of greatest importance in industrial operations. Furthermore, if these simple flows cannot be well described by continuum or molecular models, then it is not necessary to lavish time and energy to apply them to more complex flow problems. PMID:27276553

  4. Postsedimentary incorporated root and rhizomicrobial remains influence composition of loess organic matter - an approach based on lipid molecular proxies

    NASA Astrophysics Data System (ADS)

    Gocke, M.; Wiesenberg, G. L. B.

    2012-04-01

    Organic carbon (Corg) in loess-paleosol sequences is frequently used to study paleovegetation and paleoenvironmental change during Quaternary, assuming that loess organic matter derived from aboveground biomass of synsedimentary vegetation. Contrary to this traditional hypothesis, recent studies showed that postsedimentary deep-rooting plants can contribute considerable amounts of organic matter (OM) to the subsoil via roots and associated microbial biomass. This becomes evident when regarding rhizoliths, a special type of pedogenic carbonates formed by encrustation of roots with secondary CaCO3. The carbonate crust led to preservation of former root tissue, allowing assessment of rhizosphere processes and OM accumulated during the root's lifetime. We hypothesized that rhizosphere effects in loess-paleosol sequences can be quantified at a molecular level. At the late Pleistocene Nussloch section, rhizoliths occur locally abundant. Several transects, comprising rhizoliths, surrounding loess (rhizoloess) up to a distance of 10 cm from rhizoliths, and root-free reference loess, were sampled between 1 and 13 m depth and analysed for their C, n-alkane and fatty acid composition. These lipid fractions are frequently used to assess and quantify OM remains in sediments because of their relative recalcitrance. Rather uniform lipid composition in reference loess indicated its origin from grass aboveground biomass. In contrast, lipid composition of rhizoliths showed strong variation with depth, impeding a general source attribution of rhizoliths. However, several proxies including C27 as most abundant long chain n-alkane in some rhizoliths, as well as low values of average chain length and carbon perference index, indicated that rhizoliths were formed around roots of shrubs or trees. First results indicated that the former rhizosphere extended up to several cm from preserved rhizoliths. High variation in rhizolith abundance (up to 190 m-2) and size (mm to 5 cm in diameter

  5. 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. PMID:21432950

  6. A Simple Approach for Molecular Controlled Release based on Atomic Layer Deposition Hybridized Organic-Inorganic Layers

    NASA Astrophysics Data System (ADS)

    Boehler, Christian; Güder, Firat; Kücükbayrak, Umut M.; Zacharias, Margit; Asplund, Maria

    2016-01-01

    On-demand release of bioactive substances with high spatial and temporal control offers ground-breaking possibilities in the field of life sciences. However, available strategies for developing such release systems lack the possibility of combining efficient control over release with adequate storage capability in a reasonably compact system. In this study we present a new approach to target this deficiency by the introduction of a hybrid material. This organic-inorganic material was fabricated by atomic layer deposition of ZnO into thin films of polyethylene glycol, forming the carrier matrix for the substance to be released. Sub-surface growth mechanisms during this process converted the liquid polymer into a solid, yet water-soluble, phase. This layer permits extended storage for various substances within a single film of only a few micrometers in thickness, and hence demands minimal space and complexity. Improved control over release of the model substance Fluorescein was achieved by coating the hybrid material with a conducting polymer film. Single dosage and repetitive dispensing from this system was demonstrated. Release was controlled by applying a bias potential of ±0.5 V to the polymer film enabling or respectively suppressing the expulsion of the model drug. In vitro tests showed excellent biocompatibility of the presented system.

  7. A Simple Approach for Molecular Controlled Release based on Atomic Layer Deposition Hybridized Organic-Inorganic Layers

    PubMed Central

    Boehler, Christian; Güder, Firat; Kücükbayrak, Umut M.; Zacharias, Margit; Asplund, Maria

    2016-01-01

    On-demand release of bioactive substances with high spatial and temporal control offers ground-breaking possibilities in the field of life sciences. However, available strategies for developing such release systems lack the possibility of combining efficient control over release with adequate storage capability in a reasonably compact system. In this study we present a new approach to target this deficiency by the introduction of a hybrid material. This organic-inorganic material was fabricated by atomic layer deposition of ZnO into thin films of polyethylene glycol, forming the carrier matrix for the substance to be released. Sub-surface growth mechanisms during this process converted the liquid polymer into a solid, yet water-soluble, phase. This layer permits extended storage for various substances within a single film of only a few micrometers in thickness, and hence demands minimal space and complexity. Improved control over release of the model substance Fluorescein was achieved by coating the hybrid material with a conducting polymer film. Single dosage and repetitive dispensing from this system was demonstrated. Release was controlled by applying a bias potential of ±0.5 V to the polymer film enabling or respectively suppressing the expulsion of the model drug. In vitro tests showed excellent biocompatibility of the presented system. PMID:26791399

  8. A Simple Approach for Molecular Controlled Release based on Atomic Layer Deposition Hybridized Organic-Inorganic Layers.

    PubMed

    Boehler, Christian; Güder, Firat; Kücükbayrak, Umut M; Zacharias, Margit; Asplund, Maria

    2016-01-01

    On-demand release of bioactive substances with high spatial and temporal control offers ground-breaking possibilities in the field of life sciences. However, available strategies for developing such release systems lack the possibility of combining efficient control over release with adequate storage capability in a reasonably compact system. In this study we present a new approach to target this deficiency by the introduction of a hybrid material. This organic-inorganic material was fabricated by atomic layer deposition of ZnO into thin films of polyethylene glycol, forming the carrier matrix for the substance to be released. Sub-surface growth mechanisms during this process converted the liquid polymer into a solid, yet water-soluble, phase. This layer permits extended storage for various substances within a single film of only a few micrometers in thickness, and hence demands minimal space and complexity. Improved control over release of the model substance Fluorescein was achieved by coating the hybrid material with a conducting polymer film. Single dosage and repetitive dispensing from this system was demonstrated. Release was controlled by applying a bias potential of ± 0.5 V to the polymer film enabling or respectively suppressing the expulsion of the model drug. In vitro tests showed excellent biocompatibility of the presented system. PMID:26791399

  9. Molecular-based synthetic approach to new group IV materials for high-efficiency, low-cost solar cells and Si-based optoelectronics.

    PubMed

    Fang, Yan-Yan; Xie, Junqi; Tolle, John; Roucka, Radek; D'Costa, Vijay R; Chizmeshya, Andrew V G; Menendez, Jose; Kouvetakis, John

    2008-11-26

    Ge(1-x-y)Si(x)Sn(y) alloys have emerged as a new class of highly versatile IR semiconductors offering the potential for independent variation of band structure and lattice dimension, making them the first practical group IV ternary system fully compatible with Si CMOS processing. In this paper we develop and apply new synthetic protocols based on designer molecular hydrides of Si, Ge, and Sn to demonstrate this concept from a synthesis perspective. Variation of the Si/Sn ratio in the ternary leads to an entirely new family of semiconductors exhibiting tunable direct band gaps (E(o)) ranging from 0.8 to 1.2 eV at a fixed lattice constant identical to that of Ge, as required for the design of high-efficiency multijunction solar cells based on group IV/III-V hybrids. As a proof-of-concept demonstration, we fabricated lattice-matched Si(100)/Ge/SiGeSn/InGaAs architectures on low-cost Si(100) substrates for the first time. These exhibit the required optical, structural, and thermal properties, thus representing a viable starting point en route to a complete four-junction photovoltaic device. In the context of Si-Ge-Sn optoelectronic applications, we show that Ge(1-x-y)Si(x)Sn(y) alloys serve as higher-gap barrier layers for the formation of light emitting structures based on Ge(1-y)Sn(y) quantum wells grown on Si. PMID:19032100

  10. Oral cancer screening approach based on labeling exfoliated oral cells with molecularly-targeted optical contrast agents

    NASA Astrophysics Data System (ADS)

    Leautaud, Veronica; Horres, Charles R.; Bhattar, Vijayashree S.; Williams, Michelle D.; Gillenwater, Ann M.; Richards-Kortum, Rebecca R.

    2011-03-01

    Early detection is a potential key to improving the survival rates of oral cancer patients and reducing the morbidity associated with treatment. We seek to improve upon methods of detecting of early malignancies with oral brush biopsies by using immunofluorescence-based assessment of the expression of multiple well-described markers commonly overexpressed in oral cancers, such as Epidermal Growth Factor Receptor (EGFR) and Cytokeratin 8 (CK8). Furthermore, since abnormal cells are often scarce in brush biopsy samples, we seek to use magnetic microparticles targeted to these markers as a means of enriching the concentration of abnormal cells. Finally, we plan to conduct a small pilot study using these methods with brush biopsies from patients of the M. D. Anderson Cancer Center Head and Neck Clinic.

  11. Molecular systematics of the Jacks (Perciformes: Carangidae) based on mitochondrial cytochrome b sequences using parsimony, likelihood, and Bayesian approaches.

    PubMed

    Reed, David L; Carpenter, Kent E; deGravelle, Martin J

    2002-06-01

    The Carangidae represent a diverse family of marine fishes that include both ecologically and economically important species. Currently, there are four recognized tribes within the family, but phylogenetic relationships among them based on morphology are not resolved. In addition, the tribe Carangini contains species with a variety of body forms and no study has tried to interpret the evolution of this diversity. We used DNA sequences from the mitochondrial cytochrome b gene to reconstruct the phylogenetic history of 50 species from each of the four tribes of Carangidae and four carangoid outgroup taxa. We found support for the monophyly of three tribes within the Carangidae (Carangini, Naucratini, and Trachinotini); however, monophyly of the fourth tribe (Scomberoidini) remains questionable. A sister group relationship between the Carangini and the Naucratini is well supported. This clade is apparently sister to the Trachinotini plus Scomberoidini but there is uncertain support for this relationship. Additionally, we examined the evolution of body form within the tribe Carangini and determined that each of the predominant clades has a distinct evolutionary trend in body form. We tested three methods of phylogenetic inference, parsimony, maximum-likelihood, and Bayesian inference. Whereas the three analyses produced largely congruent hypotheses, they differed in several important relationships. Maximum-likelihood and Bayesian methods produced hypotheses with higher support values for deep branches. The Bayesian analysis was computationally much faster and yet produced phylogenetic hypotheses that were very similar to those of the maximum-likelihood analysis. PMID:12099802

  12. A Systematic Approach to Solvent Selection Based on Cohesive Energy Densities in a Molecular Bulk Heterojunction System

    SciTech Connect

    Walker, Bright; Tamayo, Arnold; Duong, Duc T.; Dang, Xuan-Dung; Kim, Chunki; Granstrom, Jimmy; Nguyen, Thuc-Quyen

    2011-02-15

    The solubilities of 3,6-bis(5-(benzofuran-2-yl)thiophen-2-yl)-2,5-bis(2-ethylhexyl)pyrrolo[3,4-c]pyrrole-1,4-dione (DPP(TBFu)₂) and [6,6]-phenyl-C₇₁-butyric acid methyl ester (PC₇₁BM) in a series of solvents are measured, and this data is used to calculate the Hansen solubility parameters of the two materials. The dispersion, polar, and H-bonding parameters of DPP(TBFu)₂ and PC₇₁BM were found to be (19.3, 4.8, 6.3) and (20.2, 5.4, 4.5) MPa{sup 1/2}, respectively, with an error of ± 0.8 MPa{sup 1/2}. Based on the solubility properties of the two materials, three new solvents (thiophene, trichloroethylene and carbon disulfide) were utilized for the DPP(TBFu)₂:PC₇₁BM system which, after device optimization, led to power conversion efficiencies up to 4.3%.

  13. Molecular Individual-Based Approach on Triatoma brasiliensis: Inferences on Triatomine Foci, Trypanosoma cruzi Natural Infection Prevalence, Parasite Diversity and Feeding Sources

    PubMed Central

    Almeida, Carlos Eduardo; Faucher, Leslie; Lavina, Morgane; Costa, Jane; Harry, Myriam

    2016-01-01

    We used an individual-based molecular multisource approach to assess the epidemiological importance of Triatoma brasiliensis collected in distinct sites and ecotopes in Rio Grande do Norte State, Brazil. In the semi-arid zones of Brazil, this blood sucking bug is the most important vector of Trypanosoma cruzi—the parasite that causes Chagas disease. First, cytochrome b (cytb) and microsatellite markers were used for inferences on the genetic structure of five populations (108 bugs). Second, we determined the natural T. cruzi infection prevalence and parasite diversity in 126 bugs by amplifying a mini-exon gene from triatomine gut contents. Third, we identified the natural feeding sources of 60 T. brasiliensis by using the blood meal content via vertebrate cytb analysis. Demographic inferences based on cytb variation indicated expansion events in some sylvatic and domiciliary populations. Microsatellite results indicated gene flow between sylvatic and anthropic (domiciliary and peridomiciliary) populations, which threatens vector control efforts because sylvatic population are uncontrollable. A high natural T. cruzi infection prevalence (52–71%) and two parasite lineages were found for the sylvatic foci, in which 68% of bugs had fed on Kerodon rupestris (Rodentia: Caviidae), highlighting it as a potential reservoir. For peridomiciliary bugs, Galea spixii (Rodentia: Caviidae) was the main mammal feeding source, which may reinforce previous concerns about the potential of this animal to link the sylvatic and domiciliary T. cruzi cycles. PMID:26891047

  14. Computational molecular biology approaches to ligand-target interactions

    PubMed Central

    Lupieri, Paola; Nguyen, Chuong Ha Hung; Bafghi, Zhaleh Ghaemi; Giorgetti, Alejandro; Carloni, Paolo

    2009-01-01

    Binding of small molecules to their targets triggers complex pathways. Computational approaches are keys for predictions of the molecular events involved in such cascades. Here we review current efforts at characterizing the molecular determinants in the largest membrane-bound receptor family, the G-protein-coupled receptors (GPCRs). We focus on odorant receptors, which constitute more than half GPCRs. The work presented in this review uncovers structural and energetic aspects of components of the cellular cascade. Finally, a computational approach in the context of radioactive boron-based antitumoral therapies is briefly described. PMID:20119480

  15. A combined spectroscopic, docking and molecular dynamics simulation approach to probing binding of a Schiff base complex to human serum albumin

    NASA Astrophysics Data System (ADS)

    Fani, N.; Bordbar, A. K.; Ghayeb, Y.

    2013-02-01

    The molecular mechanism of a Schiff base complex ((E)-((E)-2-(3-((E)-((E)-3(mercapto (methylthio) methylene)cyclopentylidene) amino) propylimino) cyclopentylidene) (methylthio) methanethiol) binding to Human Serum Albumin (HSA) was investigated by fluorescence quenching, absorption spectroscopy, molecular docking and molecular dynamics (MD) simulation procedures. The fluorescence emission of HSA was quenched by this Schiff base complex that has been analyzed for estimation of binding parameters. The titration of Schiff base solution by various amount of HSA was also followed by UV-Vis absorption spectroscopy and the corresponding data were analyzed by suitable models. The results revealed that this Schiff base has an ability to bind strongly to HSA and formed 1:1 complex. Energy transfer mechanism of quenching was discussed and the value of 5.45 ± 0.06 nm was calculated as the mean distance between the bound complex and the Trp residue. This is implying the high possibility of energy transfer from HSA to this Schiff base complex. Molecular docking results indicated that the main active binding site for this Schiff base complex is site III in subdomain IB. Moreover, MD simulation results suggested that this Schiff base complex can interact with HSA, without affecting the secondary structure of HSA but probably with a slight modification of its tertiary structure. MD simulations, molecular docking and experimental data reciprocally supported each other.

  16. The Secondary Organic Aerosol Processor (SOAP v1.0) model: a unified model with different ranges of complexity based on the molecular surrogate approach

    NASA Astrophysics Data System (ADS)

    Couvidat, F.; Sartelet, K.

    2014-01-01

    The Secondary Organic Aerosol Processor (SOAP v1.0) model is presented. This model is designed to be modular with different user options depending on the computing time and the complexity required by the user. This model is based on the molecular surrogate approach, in which each surrogate compound is associated with a molecular structure to estimate some properties and parameters (hygroscopicity, absorption on the aqueous phase of particles, activity coefficients, phase separation). Each surrogate can be hydrophilic (condenses only on the aqueous phase of particles), hydrophobic (condenses only on the organic phase of particles) or both (condenses on both the aqueous and the organic phases of particles). Activity coefficients are computed with the UNIFAC thermodynamic model for short-range interactions and with the AIOMFAC parameterization for medium and long-range interactions between electrolytes and organic compounds. Phase separation is determined by Gibbs energy minimization. The user can choose between an equilibrium and a dynamic representation of the organic aerosol. In the equilibrium representation, compounds in the particle phase are assumed to be at equilibrium with the gas phase. However, recent studies show that the organic aerosol (OA) is not at equilibrium with the gas phase because the organic phase could be semi-solid (very viscous liquid phase). The condensation or evaporation of organic compounds could then be limited by the diffusion in the organic phase due to the high viscosity. A dynamic representation of secondary organic aerosols (SOA) is used with OA divided into layers, the first layer at the center of the particle (slowly reaches equilibrium) and the final layer near the interface with the gas phase (quickly reaches equilibrium).

  17. Pseudospectral approach to relativistic molecular theory.

    PubMed

    Nakajima, Takahito; Hirao, Kimihiko

    2004-08-22

    The efficient relativistic Dirac-Hartree-Fock (DHF) and Dirac-Kohn-Sham (DKS) methods are proposed by an application of the pseudospectral (PS) approach. The present PS-DHF/DKS method is a relativistic extension of the PS-HF/KS method of Friesner, though we aim at higher numerical accuracy by elimination of superfluous arbitrariness. The relativistic PS-DHF/DKS method is implemented into our REL4D programs. Several PS applications to molecular systems show that the relativistic PS-DHF/DKS approach is more efficient than the traditional approach without a loss of accuracy. The present PS-DKS method successfully assigns and predicts the photoelectron spectra of hexacarbonyl complexes of tungsten and seaborgium theoretically. PMID:15303907

  18. Graph-based molecular alignment (GMA).

    PubMed

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

    2007-01-01

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

  19. The Secondary Organic Aerosol Processor (SOAP v1.0) model: a unified model with different ranges of complexity based on the molecular surrogate approach

    NASA Astrophysics Data System (ADS)

    Couvidat, F.; Sartelet, K.

    2015-04-01

    In this paper the Secondary Organic Aerosol Processor (SOAP v1.0) model is presented. This model determines the partitioning of organic compounds between the gas and particle phases. It is designed to be modular with different user options depending on the computation time and the complexity required by the user. This model is based on the molecular surrogate approach, in which each surrogate compound is associated with a molecular structure to estimate some properties and parameters (hygroscopicity, absorption into the aqueous phase of particles, activity coefficients and phase separation). Each surrogate can be hydrophilic (condenses only into the aqueous phase of particles), hydrophobic (condenses only into the organic phases of particles) or both (condenses into both the aqueous and the organic phases of particles). Activity coefficients are computed with the UNIFAC (UNIversal Functional group Activity Coefficient; Fredenslund et al., 1975) thermodynamic model for short-range interactions and with the Aerosol Inorganic-Organic Mixtures Functional groups Activity Coefficients (AIOMFAC) parameterization for medium- and long-range interactions between electrolytes and organic compounds. Phase separation is determined by Gibbs energy minimization. The user can choose between an equilibrium representation and a dynamic representation of organic aerosols (OAs). In the equilibrium representation, compounds in the particle phase are assumed to be at equilibrium with the gas phase. However, recent studies show that the organic aerosol is not at equilibrium with the gas phase because the organic phases could be semi-solid (very viscous liquid phase). The condensation-evaporation of organic compounds could then be limited by the diffusion in the organic phases due to the high viscosity. An implicit dynamic representation of secondary organic aerosols (SOAs) is available in SOAP with OAs divided into layers, the first layer being at the center of the particle (slowly

  20. Effect of Temperature on Nanophase-segregation and Transport in Polysulfone-Based Anion Exchange Membrane Fuel Cell: Molecular Dynamics Simulation Approach

    NASA Astrophysics Data System (ADS)

    Ko, Kwan; Han, Kyung; Choi, Ji; Chang, Ying; Bae, Chulsung; Jang, Seung; Georgia Tech Team; RPI Team

    2013-03-01

    The effect of temperature on hydrated polysulfone-based anion exchange membrane is studied using molecular dynamics. Various temperature conditions such as 313K, 353 K and 393K with two different water contents (10 wt % and 20 wt %) are simulated. From the viewpoint of structure-property relationship, we scrutinize the change in the nanophase-segregated structure of membrane and transport of anionic charge carrier (hydroxide) as a function of temperature. Since it is well known that the anion transport is less than the proton transport, we attempt to pursue a fundamental understanding of the difference between anion transport and proton transport. For this purpose, we simulate the polysulfone-based proton exchange membrane that has the same molecular structure and molecular weight. By analyzing the pair-correlation of charge carriers, we observe the correlation among hydroxides is much stronger than that among hydroniums. The extent of nanophase-segregation is also analyzed using structure factor profile.

  1. Density functional theory-based simulations of sum frequency generation spectra involving methyl stretching vibrations: effect of the molecular model on the deduced molecular orientation and comparison with an analytical approach

    NASA Astrophysics Data System (ADS)

    Cecchet, F.; Lis, D.; Caudano, Y.; Mani, A. A.; Peremans, A.; Champagne, B.; Guthmuller, J.

    2012-03-01

    The knowledge of the first hyperpolarizability tensor elements of molecular groups is crucial for a quantitative interpretation of the sum frequency generation (SFG) activity of thin organic films at interfaces. Here, the SFG response of the terminal methyl group of a dodecanethiol (DDT) monolayer has been interpreted on the basis of calculations performed at the density functional theory (DFT) level of approximation. In particular, DFT calculations have been carried out on three classes of models for the aliphatic chains. The first class of models consists of aliphatic chains, containing from 3 to 12 carbon atoms, in which only one methyl group can freely vibrate, while the rest of the chain is frozen by a strong overweight of its C and H atoms. This enables us to localize the probed vibrational modes on the methyl group. In the second class, only one methyl group is frozen, while the entire remaining chain is allowed to vibrate. This enables us to analyse the influence of the aliphatic chain on the methyl stretching vibrations. Finally, the dodecanethiol (DDT) molecule is considered, for which the effects of two dielectrics, i.e. n-hexane and n-dodecane, are investigated. Moreover, DDT calculations are also carried out by using different exchange-correlation (XC) functionals in order to assess the DFT approximations. Using the DFT IR vectors and Raman tensors, the SFG spectrum of DDT has been simulated and the orientation of the methyl group has then been deduced and compared with that obtained using an analytical approach based on a bond additivity model. This analysis shows that when using DFT molecular properties, the predicted orientation of the terminal methyl group tends to converge as a function of the alkyl chain length and that the effects of the chain as well as of the dielectric environment are small. Instead, a more significant difference is observed when comparing the DFT-based results with those obtained from the analytical approach, thus indicating

  2. Molecular structure and elastic properties of thermotropic liquid crystals: Integrated molecular dynamics—Statistical mechanical theory vs molecular field approach

    NASA Astrophysics Data System (ADS)

    Capar, M. Ilk; Nar, A.; Ferrarini, A.; Frezza, E.; Greco, C.; Zakharov, A. V.; Vakulenko, A. A.

    2013-03-01

    The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio.

  3. Molecular structure and elastic properties of thermotropic liquid crystals: integrated molecular dynamics--statistical mechanical theory vs molecular field approach.

    PubMed

    Ilk Capar, M; Nar, A; Ferrarini, A; Frezza, E; Greco, C; Zakharov, A V; Vakulenko, A A

    2013-03-21

    The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio

  4. Molecular Tools and Approaches for Optogenetics

    PubMed Central

    Mei, Yuan; Zhang, Feng

    2012-01-01

    The mammalian brain poses a formidable challenge to the study and treatment of neuropsychiatric diseases – owing to the complex interaction of genetic, epigenetic, and circuit-level mechanisms underlying pathogenesis. Technologies that facilitate functional dissection of distinct brain circuits are necessary for systematic identification of disease origin and therapy. Recent developments in the optogenetics technology have begun to address this challenge by enabling precise perturbation of distinct cell types based on molecular signatures, functional projections, and intracellular biochemical signaling pathways. With high temporal precision and reversible neuromodulation, optogenetics promises to improve existing disease models and advance our understanding of psychiatric conditions. In this review, we will describe the current state of molecular optogenetic tools and future directions of development. PMID:22480664

  5. A Universal Electrode Approach for Automated Electrochemical Molecular Analyses

    PubMed Central

    Sin, Mandy L. Y.; Gau, Vincent; Liao, Joseph C.; Wong, P. K.

    2014-01-01

    Transforming microfluidics-based biosensing systems from laboratory research into clinical reality remains an elusive goal despite decades of intensive research. A fundamental obstacle for the development of fully automated microfluidic diagnostic systems is the lack of an effective strategy for combining pumping, sample preparation, and detection modules into an integrated biosensing platform. Herein, we report a universal electrode approach, which incorporates DC electrolytic pumping, AC electrokinetic sample preparation, and self-assembled monolayer based electrochemical sensing on a single microfluidic platform, to automate complicated molecular analysis procedures that will enable biosensing applications in non-traditional healthcare settings. Using the universal electrode approach, major microfluidic operations required in molecular analyses, such as pumping, mixing, washing, and sensing can be performed in a single platform. We demonstrate the universal electrode platform for detecting bacterial 16S rRNA, a phylogenetic marker, toward rapid diagnostics of urinary tract infection. Since only electronic interfaces are required to operate the platform, the universal electrode approach represents an effective system integration strategy to realize the potential of microfluidics in molecular diagnostics at the point of care. PMID:24860248

  6. Discovery of novel Pim-1 kinase inhibitors by a hierarchical multistage virtual screening approach based on SVM model, pharmacophore, and molecular docking.

    PubMed

    Ren, Ji-Xia; Li, Lin-Li; Zheng, Ren-Lin; Xie, Huan-Zhang; Cao, Zhi-Xing; Feng, Shan; Pan, You-Li; Chen, Xin; Wei, Yu-Quan; Yang, Sheng-Yong

    2011-06-27

    In this investigation, we describe the discovery of novel potent Pim-1 inhibitors by employing a proposed hierarchical multistage virtual screening (VS) approach, which is based on support vector machine-based (SVM-based VS or SB-VS), pharmacophore-based VS (PB-VS), and docking-based VS (DB-VS) methods. In this approach, the three VS methods are applied in an increasing order of complexity so that the first filter (SB-VS) is fast and simple, while successive ones (PB-VS and DB-VS) are more time-consuming but are applied only to a small subset of the entire database. Evaluation of this approach indicates that it can be used to screen a large chemical library rapidly with a high hit rate and a high enrichment factor. This approach was then applied to screen several large chemical libraries, including PubChem, Specs, and Enamine as well as an in-house database. From the final hits, 47 compounds were selected for further in vitro Pim-1 inhibitory assay, and 15 compounds show nanomolar level or low micromolar inhibition potency against Pim-1. In particular, four of them were found to have new scaffolds which have potential for the chemical development of Pim-1 inhibitors. PMID:21618971

  7. Approaches to USJ Formation Beyond Molecular Implantation

    SciTech Connect

    Hatem, C.; Renau, A.; Godet, L.; Kontos, A.; Papasouliotis, G.; England, J.; Arevalo, E.

    2008-11-03

    As junction depth requirements approach sub 10 nm and the sensitivity to residual implant damage continues to increase, the capability to produce abrupt, shallow profiles while maintaining low residual damage becomes a difficult challenge. Implantation induced amorphization has been widely applied to reduce channeling tails of implanted dopant profiles for integrated circuit manufacturing. This has been required to meet aggressive junction depth targets. The problem, however, is that pre-amorphization creates high defect densities that remain near the former amorphous-crystalline interface post anneal. These end of range (EOR) defects become of greater concern as the industry begins to move towards millisecond anneal technologies. Millisecond anneal, while capable of close to diffusionless activation and abrupt junctions, has caused concern for its inability to fully repair these EOR defects. There has been a recent focus on removing traditional PAI through molecular implantation with limited success. Towards this end we have investigated alternative techniques to reduce EOR damage while maintaining the junction depth, sheet resistance and abruptness. Here we describe the results of two of these techniques. The subsequent reduction in EOR through the use of each process and the resultant Rs, junction depth and abruptness are detailed.

  8. Approaches to USJ Formation Beyond Molecular Implantation

    NASA Astrophysics Data System (ADS)

    Hatem, C.; Renau, A.; Godet, L.; Kontos, A.; Papasouliotis, G.; England, J.; Arevalo, E.

    2008-11-01

    As junction depth requirements approach sub 10 nm and the sensitivity to residual implant damage continues to increase, the capability to produce abrupt, shallow profiles while maintaining low residual damage becomes a difficult challenge. Implantation induced amorphization has been widely applied to reduce channeling tails of implanted dopant profiles for integrated circuit manufacturing. This has been required to meet aggressive junction depth targets. The problem, however, is that pre-amorphization creates high defect densities that remain near the former amorphous-crystalline interface post anneal. These end of range (EOR) defects become of greater concern as the industry begins to move towards millisecond anneal technologies. Millisecond anneal, while capable of close to diffusionless activation and abrupt junctions, has caused concern for its inability to fully repair these EOR defects. There has been a recent focus on removing traditional PAI through molecular implantation with limited success. Towards this end we have investigated alternative techniques to reduce EOR damage while maintaining the junction depth, sheet resistance and abruptness. Here we describe the results of two of these techniques. The subsequent reduction in EOR through the use of each process and the resultant Rs, junction depth and abruptness are detailed.

  9. Potential molecular wires by an iterative divergent/convergent approach. Doubling of molecular length at each iteration

    NASA Astrophysics Data System (ADS)

    Pearson, Darren L.; Schumm, Jeffry S.; Jones, Leroy, II; Tour, James M.

    1994-06-01

    We have devised an iterative convergent/divergent approach to conjugated oligomers that might serve as molecular wires. The molecular length doubles with each iteration. The systems prepared are completely monodispersed and based upon oligo(thiophene-ethynylene)s (1) and oligo(phenylene-ethynylene)s at 100 A and 128 A long, respectively. The optical and size exclusion chromatography (SEC) properties are discussed. Methods are outlined to attach end groups that might serve as molecular alligator clips.

  10. The diagnosis of BCR/ABL-negative chronic myeloproliferative diseases (CMPD): a comprehensive approach based on morphology, cytogenetics, and molecular markers.

    PubMed

    Haferlach, Torsten; Bacher, Ulrike; Kern, Wolfgang; Schnittger, Susanne; Haferlach, Claudia

    2008-01-01

    Recent years showed significant progress in the molecular characterization of the chronic myeloproliferative disorders (CMPD) which are classified according to the WHO classification of 2001 as polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia, and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome, all to be delineated from BCR/ABL-positive chronic myeloid leukemia (CML). After 2001, the detection of the high frequency of the JAK2V617F mutation in PV, CIMF, and ET, and of the FIP1L1-PDGFRA fusion gene in CEL further added important information in the diagnosis of CMPD. These findings also enhanced the importance of tyrosine kinase mutations in CMPD and paved the way to a more detailed classification and to an improved definition of prognosis using also novel minimal residual disease (MRD) markers. Simultaneously, the broadening of therapeutic strategies in the CMPD, e.g., due to reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation and the introduction of tyrosine kinase inhibitors in CML, in CEL, and in other ABL and PDGRFB rearrangements, increased the demands to diagnostics. Therefore, today, a multimodal diagnostic approach combining cytomorphology, cytogenetics, and individual molecular methods is needed in BCR/ABL-negative CMPD. A stringent diagnostic algorithm for characterization, choice of treatment, and monitoring of MRD will be proposed in this review. PMID:17938925

  11. 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.

  12. Molecular basis of glyphosate resistance: Different approaches through protein engineering

    PubMed Central

    Pollegioni, Loredano; Schonbrunn, Ernst; Siehl, Daniel

    2011-01-01

    Glyphosate (N-phosphonomethyl-glycine) is the most-used herbicide in the world: glyphosate-based formulations exhibit broad-spectrum herbicidal activity with minimal human and environmental toxicity. The extraordinary success of this simple small molecule is mainly due to the high specificity of glyphosate towards the plant enzyme enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway leading to biosynthesis of aromatic amino acids. Starting in 1996, transgenic glyphosate-resistant plants were introduced thus allowing the application of the herbicide to the crop (post-emergence) to remove emerged weeds without crop damage. This review focuses on the evolution of mechanisms of resistance to glyphosate as obtained through natural diversity, the gene shuffling approach to molecular evolution, and a rational, structure-based approach to protein engineering. In addition, we offer rationale for the means by which the modifications made have had their intended effect. PMID:21668647

  13. Model-free simulation approach to molecular diffusion tensors.

    PubMed

    Chevrot, Guillaume; Hinsen, Konrad; Kneller, Gerald R

    2013-10-21

    In the present work, we propose a simple model-free approach for the computation of molecular diffusion tensors from molecular dynamics trajectories. The method uses a rigid body trajectory of the molecule under consideration, which is constructed a posteriori by an accumulation of quaternion-based superposition fits of consecutive conformations. From the rigid body trajectory, we compute the translational and angular velocities of the molecule and by integration of the latter also the corresponding angular trajectory. All quantities can be referred to the laboratory frame and a molecule-fixed frame. The 6 × 6 diffusion tensor is computed from the asymptotic slope of the tensorial mean square displacement and, for comparison, also from the Kubo integral of the velocity correlation tensor. The method is illustrated for two simple model systems - a water molecule and a lysozyme molecule in bulk water. We give estimations of the statistical accuracy of the calculations. PMID:24160503

  14. Model-free simulation approach to molecular diffusion tensors

    NASA Astrophysics Data System (ADS)

    Chevrot, Guillaume; Hinsen, Konrad; Kneller, Gerald R.

    2013-10-01

    In the present work, we propose a simple model-free approach for the computation of molecular diffusion tensors from molecular dynamics trajectories. The method uses a rigid body trajectory of the molecule under consideration, which is constructed a posteriori by an accumulation of quaternion-based superposition fits of consecutive conformations. From the rigid body trajectory, we compute the translational and angular velocities of the molecule and by integration of the latter also the corresponding angular trajectory. All quantities can be referred to the laboratory frame and a molecule-fixed frame. The 6 × 6 diffusion tensor is computed from the asymptotic slope of the tensorial mean square displacement and, for comparison, also from the Kubo integral of the velocity correlation tensor. The method is illustrated for two simple model systems - a water molecule and a lysozyme molecule in bulk water. We give estimations of the statistical accuracy of the calculations.

  15. Appraisal of molecular tailoring approach for large clusters

    NASA Astrophysics Data System (ADS)

    Sahu, Nityananda; Yeole, Sachin D.; Gadre, Shridhar R.

    2013-03-01

    High level ab initio investigations on molecular clusters are generally restricted to those of small size essentially due to the nonlinear scaling of corresponding computational cost. Molecular tailoring approach (MTA) is a fragmentation-based method, which offers an economical and efficient route for studying larger clusters. However, due to its approximate nature, the MTA-energies carry some errors vis-à-vis their full calculation counterparts. These errors in the MTA-energies are reduced by grafting the correction at a lower basis set (e.g., 6-31+G(d)) onto a higher basis set (e.g., aug-cc-pvdz or aug-cc-pvtz) calculation at MP2 level of theory. Further, better estimates of energies are obtained by making use of many-body interaction analysis. For this purpose, R-goodness (Rg) parameters for the three- and four-body interactions in a fragmentation scheme are proposed. The procedure employing grafting and many-body analysis has been tested out on molecular clusters of water, benzene, acetylene and carbon dioxide. It is found that for the fragmentation scheme having higher three- and four-body Rg-values, the errors in MTA-grafted energies are reduced typically to ˜0.2 mH at MP2 level calculation. Coupled with the advantage in terms of computational resources and CPU time, the present method opens a possibility of accurate treatment of large molecular clusters.

  16. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers

    PubMed Central

    Bauer, Michael; Riedemann, Niels C.; Hartog, Christiane S.

    2012-01-01

    Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

  17. New approaches to sepsis: molecular diagnostics and biomarkers.

    PubMed

    Reinhart, Konrad; Bauer, Michael; Riedemann, Niels C; Hartog, Christiane S

    2012-10-01

    Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

  18. Insect pathogens: molecular approaches and techniques

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book serves as a primer for molecular techniques in insect pathology and is tailored for a wide scientific audience. Contributing authors are internationally recognized experts. The book comprises four sections: 1) pathogen identification and diagnostics, 2) pathogen population genetics and p...

  19. An iTRAQ-Based Proteomics Approach to Clarify the Molecular Physiology of Somatic Embryo Development in Prince Rupprecht's Larch (Larix principis-rupprechtii Mayr)

    PubMed Central

    Zhao, Jian; Li, Hui; Fu, Shuangbin; Chen, Bo; Sun, Wenting; Zhang, Junqi; Zhang, Jinfeng

    2015-01-01

    Prince Rupprecht's larch (Larix principis-rupprechtii Mayr) is a native high-value forest tree species in North China whose clonal propagation through somatic embryogenesis (SE) has the potential to rapidly capture the benefits of breeding or genetic engineering programs and to improve raw material uniformity and quality. To date, research has focused on clarifying the molecular mechanism of SE, but proteomic studies are still in the early stages. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) analysis was performed on three developmental stages of SE in L. principis-rupprechtii in an attempt to identify a wide range of proteins that are regulated differentially during this process. Proteins were extracted and analyzed from the pro-embryogenic mass (PEM), globular embryo (GE), and cotyledon embryo (CE) stages of embryo development. We detected 503 proteins in total and identified 96 proteins expressed differentially during different developmental stages. The identified proteins were analyzed further to provide information about their expression patterns and functions during SE. Four clusters of proteins based on shared expression profiles were generated. Functional analysis showed that proteins involved in primary metabolism, phosphorylation, and oxidation reduction were upregulated during somatic embryo development. This work provides novel insights into the process of larch embryo development in vitro and a basis for further study of the biological process and opportunities for practical application of this knowledge. PMID:25781987

  20. An iTRAQ-based proteomics approach to clarify the molecular physiology of somatic embryo development in Prince Rupprecht's larch (Larix principis-rupprechtii Mayr).

    PubMed

    Zhao, Jian; Li, Hui; Fu, Shuangbin; Chen, Bo; Sun, Wenting; Zhang, Junqi; Zhang, Jinfeng

    2015-01-01

    Prince Rupprecht's larch (Larix principis-rupprechtii Mayr) is a native high-value forest tree species in North China whose clonal propagation through somatic embryogenesis (SE) has the potential to rapidly capture the benefits of breeding or genetic engineering programs and to improve raw material uniformity and quality. To date, research has focused on clarifying the molecular mechanism of SE, but proteomic studies are still in the early stages. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) analysis was performed on three developmental stages of SE in L. principis-rupprechtii in an attempt to identify a wide range of proteins that are regulated differentially during this process. Proteins were extracted and analyzed from the pro-embryogenic mass (PEM), globular embryo (GE), and cotyledon embryo (CE) stages of embryo development. We detected 503 proteins in total and identified 96 proteins expressed differentially during different developmental stages. The identified proteins were analyzed further to provide information about their expression patterns and functions during SE. Four clusters of proteins based on shared expression profiles were generated. Functional analysis showed that proteins involved in primary metabolism, phosphorylation, and oxidation reduction were upregulated during somatic embryo development. This work provides novel insights into the process of larch embryo development in vitro and a basis for further study of the biological process and opportunities for practical application of this knowledge. PMID:25781987

  1. Fluorescence lifetime-based optical molecular imaging.

    PubMed

    Kumar, Anand T N

    2011-01-01

    Fluorescence lifetime is a powerful contrast mechanism for in vivo molecular imaging. In this chapter, we describe instrumentation and methods to optimally exploit lifetime contrast using a time domain fluorescence tomography system. The key features of the system are the use of point excitation in free-space using ultrashort laser pulses and non-contact detection using a gated, intensified CCD camera. The surface boundaries of the imaging volume are acquired using a photogrammetric camera integrated with the imaging system, and implemented in theoretical models of light propagation in biological tissue. The time domain data are optimally analyzed using a lifetime-based tomography approach, which is based on extracting a tomographic set of lifetimes and decay amplitudes from the long time decay portion of the time domain data. This approach improves the ability to locate in vivo targets with a resolution better than conventional optical methods. The application of time domain lifetime multiplexing and tomography are illustrated using phantoms and tumor bearing mouse model of breast adenocarcinoma. In the latter application, the time domain approach allows an improved detection of fluorescent protein signals from intact nude mice in the presence of background autofluorescence. This feature has potential applications for longitudinal pre-clinical evaluation of drug treatment response as well as to address fundamental questions related to tumor physiology and metastasis. PMID:21153381

  2. Skull base approaches in neurosurgery

    PubMed Central

    2010-01-01

    The skull base surgery is one of the most demanding surgeries. There are different structures that can be injured easily, by operating in the skull base. It is very important for the neurosurgeon to choose the right approach in order to reach the lesion without harming the other intact structures. Due to the pioneering work of Cushing, Hirsch, Yasargil, Krause, Dandy and other dedicated neurosurgeons, it is possible to address the tumor and other lesions in the anterior, the mid-line and the posterior cranial base. With the transsphenoidal, the frontolateral, the pterional and the lateral suboccipital approach nearly every region of the skull base is exposable. In the current state many different skull base approaches are described for various neurosurgical diseases during the last 20 years. The selection of an approach may differ from country to country, e.g., in the United States orbitozygomaticotomy for special lesions of the anterior skull base or petrosectomy for clivus meningiomas, are found more frequently than in Europe. The reason for writing the review was the question: Are there keyhole approaches with which someone can deal with a vast variety of lesions in the neurosurgical field? In my opinion the different surgical approaches mentioned above cover almost 95% of all skull base tumors and lesions. In the following text these approaches will be described. These approaches are: 1) pterional approach 2) frontolateral approach 3) transsphenoidal approach 4) suboccipital lateral approach These approaches can be extended and combined with each other. In the following we want to enhance this philosophy. PMID:20602753

  3. Molecular phylogeny and a modified approach of character-based barcoding refining the taxonomy of New Caledonian freshwater gastropods (Caenogastropoda, Truncatelloidea, Tateidae).

    PubMed

    Zielske, Susan; Haase, Martin

    2015-08-01

    The islands of New Caledonia represent one of the world's biodiversity hotspots with many endemic species including freshwater gastropods of the family Tateidae. A phylogenetic analysis based on the mitochondrial COI and 16S rRNA and the nuclear ITS2 genes revealed two cryptic genera, Crosseana gen. n. and Novacaledonia gen. n. In order to provide character-based diagnoses we modified a DNA barcoding approach identifying strings of pairwise diagnostic characters, i.e. alignment positions, at which two genera are alternatively fixed for different nucleotides. The combination or string of all pairwise diagnostic characters was unique for each genus. Inconsistent mitochondrial and nuclear topologies suggest that Hemistomia cockerelli Haase and Bouchet, 1998 and H. fabrorum Haase and Bouchet, 1998, two morphologically well-defined species, hybridize. The age of the most recent common ancestor of the New Caledonian radiation of Tateidae was estimated at 24.6±9.5 MY. These findings are in line with the notion that New Caledonia is rather a Darwinian island that was colonized after an extended phase of submergence - in case of the tateids probably from Australia - despite being a fragment of Gondwanaland. PMID:25929789

  4. Bioconjugate-Based Molecular Umbrellas

    PubMed Central

    Janout, Vaclav; Regen, Steven L.

    2009-01-01

    Molecular umbrellas are “amphomorphic” compounds that can produce a hydrophobic or a hydrophilic exterior when exposed to a hydrophobic or hydrophilic microenvironment, respectively. Such molecules are composed of two or more facial amphiphiles that are connected to a central scaffold. Molecular umbrellas that have been synthesized to date, using bile acids as umbrella “walls”, polyamines such as spermidine and spermine as scaffold material, and L-lysine as “branches”, have been found capable of transporting certain hydrophilic peptides, nucleotides, and oligonucleotides across liposomal membranes by passive diffusion. They have also have been shown to increase in the water solubility and hydrolytic stability of a hydrophobic drug, and to exhibit significant antiviral activity. The ability of a fluorescently-labeled molecular umbrella to readily enter live HeLa cells suggests that such conjugates could find use as drug carriers. PMID:19053303

  5. A Rapid Molecular Approach for Chromosomal Phasing

    PubMed Central

    Legler, Tina; Cooper, Samantha; Klitgord, Niels; Karlin-Neumann, George; Wong, Catherine; Hodges, Shawn; Koehler, Ryan; Tzonev, Svilen; McCarroll, Steven A.

    2015-01-01

    Determining the chromosomal phase of pairs of sequence variants – the arrangement of specific alleles as haplotypes – is a routine challenge in molecular genetics. Here we describe Drop-Phase, a molecular method for quickly ascertaining the phase of pairs of DNA sequence variants (separated by 1-200 kb) without cloning or manual single-molecule dilution. In each Drop-Phase reaction, genomic DNA segments are isolated in tens of thousands of nanoliter-sized droplets together with allele-specific fluorescence probes, in a single reaction well. Physically linked alleles partition into the same droplets, revealing their chromosomal phase in the co-distribution of fluorophores across droplets. We demonstrated the accuracy of this method by phasing members of trios (revealing 100% concordance with inheritance information), and demonstrate a common clinical application by phasing CFTR alleles at genomic distances of 11–116 kb in the genomes of cystic fibrosis patients. Drop-Phase is rapid (requiring less than 4 hours), scalable (to hundreds of samples), and effective at long genomic distances (200 kb). PMID:25739099

  6. Ab initio investigation of benzene clusters: Molecular tailoring approach

    NASA Astrophysics Data System (ADS)

    Mahadevi, A. Subha; Rahalkar, Anuja P.; Gadre, Shridhar R.; Sastry, G. Narahari

    2010-10-01

    An exhaustive study on the clusters of benzene (Bz)n, n =2-8, at MP2/6-31++G∗∗ level of theory is reported. The relative strengths of CH-π and π-π interactions in these aggregates are examined, which eventually govern the pattern of cluster formation. A linear scaling method, viz., molecular tailoring approach (MTA), is efficiently employed for studying the energetics and growth patterns of benzene clusters consisting up to eight benzene (Bz) units. Accuracy of MTA-based calculations is appraised by performing the corresponding standard calculations wherever possible, i.e., up to tetramers. For benzene tetramers, the error introduced in energy is of the order of 0.1 mH (˜0.06 kcal/mol). Although for higher clusters the error may build up, further corrections based on many-body interaction energy analysis substantially reduce the error in the MTA-estimate. This is demonstrated for a prototypical case of benzene hexamer. A systematic way of building up a cluster of n monomers (n-mer) which employs molecular electrostatic potential of an (n -1)-mer is illustrated. The trends obtained using MTA method are essentially identical to those of the standard methods in terms of structure and energy. In summary, this study clearly brings out the possibility of effecting such large calculations, which are not possible conventionally, by the use of MTA without a significant loss of accuracy.

  7. Molecular partitioning based on the kinetic energy density

    NASA Astrophysics Data System (ADS)

    Noorizadeh, Siamak

    2016-05-01

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

  8. Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification.

    PubMed

    Toczek, Jakub; Meadows, Judith L; Sadeghi, Mehran M

    2016-01-01

    Selection of patients for abdominal aortic aneurysm repair is currently based on aneurysm size, growth rate, and symptoms. Molecular imaging of biological processes associated with aneurysm growth and rupture, for example, inflammation and matrix remodeling, could improve patient risk stratification and lead to a reduction in abdominal aortic aneurysm morbidity and mortality. (18)F-fluorodeoxyglucose-positron emission tomography and ultrasmall superparamagnetic particles of iron oxide magnetic resonance imaging are 2 novel approaches to abdominal aortic aneurysm imaging evaluated in clinical trials. A variety of other tracers, including those that target inflammatory cells and proteolytic enzymes (eg, integrin αvβ3 and matrix metalloproteinases), have proven effective in preclinical models of abdominal aortic aneurysm and show great potential for clinical translation. PMID:26763279

  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. Molecular approach to intracellular cargo transport

    NASA Astrophysics Data System (ADS)

    Yildiz, Ahmet

    2010-03-01

    Landmark discoveries in the study of cytoplasmic motors have been made through advances in single molecule biophysics and detailed mechanistic models exist for kinesin and dynein. However, the function of motors in physiological conditions has not been carefully tested. In cells, more than few dyneins can attach to the same cargo and interact with the opposite polarity motors of kinesin. To study the molecular crosstalk between the motors, we have used intraflagellar transport (IFT) in Chlamydomonas reinhardtii as a model system. Ultrahigh spatio-temporal tracking of single cargo movement showed that IFT particles move for long distances unidirectionally with 8 nm increments, agreeing with measured step sizes of kinesin and dynein. To measure how many motors transport each cargo, we have linked large polystyrene beads to internal IFT particles through a transmembrane protein. Force measurements indicated that, on average, 3-4 motors transport cargoes in each direction. The results showed that IFT motors are tightly coordinated and might be involved in recycling each other to the appropriate end of the flagellum.

  12. Molecular Approach to Allergy Diagnosis and Therapy

    PubMed Central

    Wolf, Martin; Wallner, Michael

    2014-01-01

    Presently, allergy diagnosis and therapy procedures are undergoing a transition phase in which allergen extracts are being step-by-step replaced by molecule-based products. The new developments will allow clinicians to obtain detailed information on sensitization patterns, more accurate interpretation of allergic symptoms, and thus improved patients' management. In this respect, recombinant technology has been applied to develop this new generation of molecule-based allergy products. The use of recombinant allergens allows full validation of identity, quantity, homogeneity, structure, aggregation, solubility, stability, IgE-binding and the biologic potency of the products. In contrast, such parameters are extremely difficult to assay and standardize for extract-based products. In addition to the possibility of bulk production of wild type molecules for diagnostic purposes, recombinant technology opened the possibility of developing safer and more efficacious products for allergy therapy. A number of molecule-based hypoallergenic preparations have already been successfully evaluated in clinical trials, bringing forward the next generation of allergy vaccines. In this contribution, we review the latest developments in allergen characterization, molecule-based allergy diagnosis, and the application of recombinant allergens in therapeutic setups. A comprehensive overview of clinical trials using recombinant allergens as well as synthetic peptides is presented. PMID:24954310

  13. Zeroth-order regular approximation approach to molecular parity violation

    SciTech Connect

    Berger, Robert; Langermann, Norbert; Wuellen, Christoph van

    2005-04-01

    We present an ab initio (quasirelativistic) two-component approach to the computation of molecular parity-violating effects which is based on the zeroth-order regular approximation (ZORA). As a first application, we compute the parity-violating energy differences between various P and M conformations of C{sub 2}-symmetric molecules belonging to the series H{sub 2}X{sub 2} with X=O, S, Se, Te, Po. The results are compared to previously reported (relativistic) four-component Dirac-Hartree-Fock-Coulomb (DHFC) data. Relative deviations between ZORA and DHFC values are well below 2% for diselane and the heavier homologs whereas somewhat larger relative deviations are observed for the lighter homologs. The larger deviations for lighter systems are attributed to the (nonlocal) exchange terms coupling large and small components, which have been neglected in the present ZORA implementation. For heavier systems these play a minor role, which explains the good performance of the ZORA approach. An excellent performance, even for lighter systems, is expected for a related density-functional-theory-based ZORA because then the exchange terms coupling large and small components are absent.

  14. [Molecular bases of cancer immunology].

    PubMed

    Barrera-Rodríguez, R; Peralta-Zaragoza, O; Madrid-Marina, V

    1995-01-01

    The immune system is a tight network of different types of cells and molecules. The coordinated action of these elements mounts a precise immune response against tumor cells. However, these cells present several escape mechanisms, leading to tumor progression. This paper shows several cellular and molecular events involved in the regulation of the immune response against tumor cells. The interaction of several molecules such as MHC, TcR, adhesins, tumor antigens and cytokines are discussed, as well as the most recent knowledge about escape mechanisms and immunotherapy. PMID:7502157

  15. Coordination-Cluster-Based Molecular Magnetic Refrigerants.

    PubMed

    Zhang, Shaowei; Cheng, Peng

    2016-08-01

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

  16. Preparation of a pipette tip-based molecularly imprinted solid-phase microextraction monolith by epitope approach and its application for determination of enkephalins in human cerebrospinal fluid.

    PubMed

    Li, Hua; Li, Dan

    2015-11-10

    In this study, a novel molecularly imprinted polymer (MIP) monolith for highly selective extraction of enkephalins was synthesized and prepared in a micropipette tip using epitope imprinting technique. The synthesized MIPs were characterized by scanning electron microscope (SEM) and infrared spectroscopy. A molecularly imprinted solid-phase microextraction (MISPME) method was developed for extraction of enkephalins in aqueous solutions. The parameters affecting MISPME were optimized. The results indicated that this MIP monolith exhibited specific recognition capability, high enrichment efficiency and excellent reusability for enkephalins. MALDI-TOF MS analysis demonstrated that this MIP monolith can act as a useful tool for highly selective purification and enrichment of enkephalin, a kind of low abundance protein, from high-abundance proteins in human cerebrospinal fluids (CSF). Employed this MIP monolith as solid-phase microextraction column, quantitative assay of enkephalins in human CSF was developed by HPLC-ultraviolet (UV) detection in this work. The detection limits were 0.05-0.08nM. This MISPME/HPLC-UV method was used to quantify Met-enkephalin and Leu-enkephalin levels in the CSF of patients with cancer pain. PMID:26263061

  17. Quantum pharmacology for infectious diseases: a molecular connectivity approach.

    PubMed

    Singh, Shailza

    2012-09-01

    Infectious diseases are a major cause of global health, economic and social problems. Relationship between the infectious diseases and drugs designed to combat them can be understood by the Quantum Pharmacology approach. Quantum pharmacology which is an amalgamation of chemistry, quantum mechanics and computer modeling aims to understand the structure activity relationship of a drug. As compared to the classical MM, the hybrid QM/MM approach which takes into account the quantum mechanics along with the molecular mechanics facilitates the simulation of biological structures with greater accuracy and speed. This review highlights the importance of quantum mechanics for a better understanding of molecular systems and QSAR studies. PMID:22738083

  18. Molecular Approaches for Optimizing Vitamin D Supplementation.

    PubMed

    Carlberg, Carsten

    2016-01-01

    Vitamin D can be synthesized endogenously within UV-B exposed human skin. However, avoidance of sufficient sun exposure via predominant indoor activities, textile coverage, dark skin at higher latitude, and seasonal variations makes the intake of vitamin D fortified food or direct vitamin D supplementation necessary. Vitamin D has via its biologically most active metabolite 1α,25-dihydroxyvitamin D and the transcription factor vitamin D receptor a direct effect on the epigenome and transcriptome of many human tissues and cell types. Different interpretation of results from observational studies with vitamin D led to some dispute in the field on the desired optimal vitamin D level and the recommended daily supplementation. This chapter will provide background on the epigenome- and transcriptome-wide functions of vitamin D and will outline how this insight may be used for determining of the optimal vitamin D status of human individuals. These reflections will lead to the concept of a personal vitamin D index that may be a better guideline for an optimized vitamin D supplementation than population-based recommendations. PMID:26827955

  19. Low energy isomers of (H{sub 2}O){sub 25} from a hierarchical method based on Monte Carlo temperature basin paving and molecular tailoring approaches benchmarked by MP2 calculations

    SciTech Connect

    Sahu, Nityananda; Gadre, Shridhar R. E-mail: sotiris.xantheas@pnnl.gov; Rakshit, Avijit; Bandyopadhyay, Pradipta; Miliordos, Evangelos; Xantheas, Sotiris S. E-mail: sotiris.xantheas@pnnl.gov

    2014-10-28

    We report new global minimum candidate structures for the (H{sub 2}O){sub 25} cluster that are lower in energy than the ones reported previously and correspond to hydrogen bonded networks with 42 hydrogen bonds and an interior, fully coordinated water molecule. These were obtained as a result of a hierarchical approach based on initial Monte Carlo Temperature Basin Paving sampling of the cluster's Potential Energy Surface with the Effective Fragment Potential, subsequent geometry optimization using the Molecular Tailoring Approach with the fragments treated at the second order Møller-Plesset (MP2) perturbation (MTA-MP2) and final refinement of the entire cluster at the MP2 level of theory. The MTA-MP2 optimized cluster geometries, constructed from the fragments, were found to be within <0.5 kcal/mol from the minimum geometries obtained from the MP2 optimization of the entire (H{sub 2}O){sub 25} cluster. In addition, the grafting of the MTA-MP2 energies yields electronic energies that are within <0.3 kcal/mol from the MP2 energies of the entire cluster while preserving their energy rank order. Finally, the MTA-MP2 approach was found to reproduce the MP2 harmonic vibrational frequencies, constructed from the fragments, quite accurately when compared to the MP2 ones of the entire cluster in both the HOH bending and the OH stretching regions of the spectra.

  20. A microwave molecular solution based approach towards high-κ-tantalum(V)oxide nanoparticles: synthesis, dielectric properties and electron paramagnetic resonance spectroscopic studies of their defect chemistry.

    PubMed

    Hoffmann, R C; Kaloumenos, M; Spiehl, D; Erdem, E; Repp, S; Weber, S; Schneider, J J

    2015-12-21

    Stable dispersions of tantalum oxide nanoparticles are accessible from solutions of tantalum(V) complexes with a mixed malonato and alkanolato ligand sphere in ethoxyethanol by microwave processing. The malonato ligand is cleaved during decomposition and acetic acid or acetic acid esters are formed as derived from in situ spectroscopic studies. The solubility of the tantalum precursor and the obtained particle size therefrom depend strongly on the type of alkanolato ligand moiety. Dispersions of the molecular complexes possess good film forming properties. Films with low surface roughness can be obtained by spincoating. These exhibited a dielectric constant of about 15 and disruptive strengths above 1.5 MV cm(-1). The electrical measurements indicate that the presence of moisture is detrimental with respect to the dielectric performance of the films. After removal of the solvent from the suspensions of the nanoparticles, the residue can be redispersed in aprotic solvents. The particles can be isolated therefrom by precipitation with pentane. XRD and HRTEM indicate that the material remains amorphous up to temperatures of 750 °C. XPS proved that only Ta2O5 is formed as lower oxidation states of Ta cannot be detected. A detailed EPR study allows us to gain insight into the surface defect chemistry. Multiple types of oxygen vacancies exist at the surface of the Ta2O5 particles which are influenced by additional calcination and annealing in a vacuum. PMID:26566047

  1. Accurate Molecular Polarizabilities Based on Continuum Electrostatics

    PubMed Central

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

    2013-01-01

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

  2. Ultrathin inorganic molecular nanowire based on polyoxometalates.

    PubMed

    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

  3. 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

  4. Development of 3D-QSAR model for acetylcholinesterase inhibitors using a combination of fingerprint, molecular docking, and structure-based pharmacophore approaches

    EPA Science Inventory

    Acetylcholinesterase (AChE), a serine hydrolase vital for regulating the neurotransmitter acetylcholine in animals, has been used as a target for drugs and pesticides. With the increasing availability of AChE crystal structures, with or without ligands bound, structure-based appr...

  5. Bioassays Based on Molecular Nanomechanics

    DOE PAGESBeta

    Majumdar, Arun

    2002-01-01

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

  6. Dual-tracer background subtraction approach for fluorescent molecular tomography

    PubMed Central

    Holt, Robert W.; El-Ghussein, Fadi; Davis, Scott C.; Samkoe, Kimberley S.; Gunn, Jason R.; Leblond, Frederic

    2013-01-01

    Abstract. Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction approaches. PMID:23292612

  7. Carbogenic molecular sieves for reaction and separation by design: A novel approach to shape selective super base, super acid and catalytic membranes. Final report

    SciTech Connect

    Foley, Henry C.

    2002-03-18

    This report details the findings of three years of research plus one year of a no-cost extension. Primary results are the work with supported nanoporous carbon membranes for separation and reaction as well as with cesium-nanoporous carbon catalysts. The work resulted in 17 plus 2 papers (2 are in progress) and partial or full support for five Ph.D. students. Two patents were filed based on this research.

  8. Fractal Globules: A New Approach to Artificial Molecular Machines

    PubMed Central

    Avetisov, Vladik A.; Ivanov, Viktor A.; Meshkov, Dmitry A.; Nechaev, Sergei K.

    2014-01-01

    The over-damped relaxation of elastic networks constructed by contact maps of hierarchically folded fractal (crumpled) polymer globules was investigated in detail. It was found that the relaxation dynamics of an anisotropic fractal globule is very similar to the behavior of biological molecular machines like motor proteins. When it is perturbed, the system quickly relaxes to a low-dimensional manifold, M, with a large basin of attraction and then slowly approaches equilibrium, not escaping M. Taking these properties into account, it is suggested that fractal globules, even those made by synthetic polymers, are artificial molecular machines that can transform perturbations into directed quasimechanical motion along a defined path. PMID:25418305

  9. Fractal globules: a new approach to artificial molecular machines.

    PubMed

    Avetisov, Vladik A; Ivanov, Viktor A; Meshkov, Dmitry A; Nechaev, Sergei K

    2014-11-18

    The over-damped relaxation of elastic networks constructed by contact maps of hierarchically folded fractal (crumpled) polymer globules was investigated in detail. It was found that the relaxation dynamics of an anisotropic fractal globule is very similar to the behavior of biological molecular machines like motor proteins. When it is perturbed, the system quickly relaxes to a low-dimensional manifold, M, with a large basin of attraction and then slowly approaches equilibrium, not escaping M. Taking these properties into account, it is suggested that fractal globules, even those made by synthetic polymers, are artificial molecular machines that can transform perturbations into directed quasimechanical motion along a defined path. PMID:25418305

  10. 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.

  11. Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zamfir, Alina D.; Serb, Alina; Vukeli, Željka; Flangea, Corina; Schiopu, Catalin; Fabris, Dragana; Kalanj-Bognar, Svjetlana; Capitan, Florina; Sisu, Eugen

    2011-12-01

    Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di- O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.

  12. A Systems Biology-Based Approach to Uncovering the Molecular Mechanisms Underlying the Effects of Dragon's Blood Tablet in Colitis, Involving the Integration of Chemical Analysis, ADME Prediction, and Network Pharmacology

    PubMed Central

    Gao, Xiumei; Zhai, Huaqiang; Lin, Na; Tang, Shihuan; Liang, Rixin; Ma, Yan; Li, Defeng; Zhang, Yi; Zhu, Guangrong; Yang, Hongjun; Huang, Luqi

    2014-01-01

    Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment. PMID:25068885

  13. 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

  14. A molecular diagnostic approach able to detect the recurrent genetic prognostic factors typical of presenting myeloma

    PubMed Central

    Boyle, Eileen M; Proszek, Paula Z; Kaiser, Martin F; Begum, Dil; Dahir, Nasrin; Savola, Suvi; Wardell, Christopher P; Leleu, Xavier; Ross, Fiona M; Chiecchio, Laura; Cook, Gordon; Drayson, Mark T; Owen, Richard G; Ashcroft, John M; Jackson, Graham H; Anthony Child, James; Davies, Faith E; Walker, Brian A; Morgan, Gareth J

    2015-01-01

    Risk stratification in myeloma requires an accurate assessment of the presence of a range of molecular abnormalities including the differing IGH translocations and the recurrent copy number abnormalities that can impact clinical behavior. Currently, interphase fluorescence in situ hybridization is used to detect these abnormalities. High failure rates, slow turnaround, cost, and labor intensiveness make it difficult and expensive to use in routine clinical practice. Multiplex ligation-dependent probe amplification (MLPA), a molecular approach based on a multiplex polymerase chain reaction method, offers an alternative for the assessment of copy number changes present in the myeloma genome. Here, we provide evidence showing that MLPA is a powerful tool for the efficient detection of copy number abnormalities and when combined with expression assays, MLPA can detect all of the prognostically relevant molecular events which characterize presenting myeloma. This approach opens the way for a molecular diagnostic strategy that is efficient, high throughput, and cost effective. PMID:25287954

  15. Modern Physical Chemistry: A Molecular Approach by George H. Duffey

    NASA Astrophysics Data System (ADS)

    Ranck, John P.

    2001-08-01

    The text has been carefully edited; I found no mathematical or typographical errors.

    Literature Cited

    1. Duffey, G. H. Physical Chemistry; McGraw-Hill: New York, 1962.
    2. Barrow, G. M. Physical Chemistry; McGraw-Hill: New York, 1961.
    3. McQuarrie, D. A.; Simon, J. D. Physical Chemistry: A Molecular Approach; University Science Books: Sausalito, CA, 1997.

  16. Epitaxial growth simulation employing a combined molecular dynamics and Monte Carlo approach

    SciTech Connect

    Grein, C.H.; Benedek, R.; Rubia, T. de la

    1995-07-01

    The epitaxial growth of Ge on Si(OO1) is simulated by employing a hybrid approach based on molecular dynamics to describe the initial kinetic behavior of deposited adatoms and Monte Carlo displacements to account for subsequent equilibration. This method is well suited to describe initial nucleation and growth. Stillinger-Weber potentials are employed to describe interatomic interactions.

  17. [Molecular based targets and endometrial cancer].

    PubMed

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

    2015-01-01

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

  18. 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

  19. Molecular profiles to biology and pathways: a systems biology approach.

    PubMed

    Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

    2016-01-01

    Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters. PMID:27311441

  20. Comparative molecular approaches in Prader-Willi syndrome diagnosis.

    PubMed

    Botezatu, Anca; Puiu, Maria; Cucu, Natalia; Diaconu, Carmen C; Badiu, C; Arsene, C; Iancu, Iulia V; Plesa, Adriana; Anton, Gabriela

    2016-01-10

    Prader-Willi and Angelman syndromes are two distinct neurogenetic disorders caused by chromosomal deletions, uniparental disomy or loss of the imprinted gene expression in the 15q11-q13 region. PWS results from the lack of the paternally expressed gene contribution in the region. The aim of our study was to compare a new molecular approach based on the quantification of the expression of non-imprinted bi-allelic gene (NIPA1 and OCA2) with in house MS-PCR and the MS-MLPA test. Blood samples were collected from 12 patients, clinical criteria positives for Prader-Willi syndrome. DNA and RNA samples were isolated from white blood cells. Epigenetic changes at SNRPN gene locus were evaluated by MS-PCR technique. The expression levels of two non-imprinted genes (NIPA1 and OCA2) were evaluated in qReal-Time PCR, in order to identify type 1 and type 2 deletions. SALSA MS-MLPA kit ME028 was used to detect copy number changes and to analyze CpG islands methylation of the 15q11 region. MS-MLPA test confirmed that 8/12 patients presented different types of deletion at the SNRPN gene level (promoter, introns, and exons) and 4/8 displayed type 1 or type 2 deletion. In children with 15q11-13 deletions, the decreased level of NIPA1and OCA2 gene expression is related to chromosomal abnormality in the investigated area. The deletions were confirmed by MS-MLPA analysis, thus recommending NIPA1 and OCA2 gene expression as an alternate method to investigate deletions. PMID:26335514

  1. Molecular Characterization of Transgenic Events Using Next Generation Sequencing Approach

    PubMed Central

    Mammadov, Jafar; Ye, Liang; Soe, Khaing; Richey, Kimberly; Cruse, James; Zhuang, Meibao; Gao, Zhifang; Evans, Clive; Rounsley, Steve; Kumpatla, Siva P.

    2016-01-01

    Demand for the commercial use of genetically modified (GM) crops has been increasing in light of the projected growth of world population to nine billion by 2050. A prerequisite of paramount importance for regulatory submissions is the rigorous safety assessment of GM crops. One of the components of safety assessment is molecular characterization at DNA level which helps to determine the copy number, integrity and stability of a transgene; characterize the integration site within a host genome; and confirm the absence of vector DNA. Historically, molecular characterization has been carried out using Southern blot analysis coupled with Sanger sequencing. While this is a robust approach to characterize the transgenic crops, it is both time- and resource-consuming. The emergence of next-generation sequencing (NGS) technologies has provided highly sensitive and cost- and labor-effective alternative for molecular characterization compared to traditional Southern blot analysis. Herein, we have demonstrated the successful application of both whole genome sequencing and target capture sequencing approaches for the characterization of single and stacked transgenic events and compared the results and inferences with traditional method with respect to key criteria required for regulatory submissions. PMID:26908260

  2. Computational approaches to detect allosteric pathways in transmembrane molecular machines.

    PubMed

    Stolzenberg, Sebastian; Michino, Mayako; LeVine, Michael V; Weinstein, Harel; Shi, Lei

    2016-07-01

    Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings, many of which have therapeutic implications, however, have only become accessible in synergy with molecular modeling and simulations. Here, we review some recent computational approaches that analyze allosteric coupling networks (ACNs) in transmembrane proteins, and in particular the recently developed Protein Interaction Analyzer (PIA) designed to study ACNs in the structural ensembles sampled by molecular dynamics simulations. The power of these computational approaches in interrogating the functional mechanisms of transmembrane proteins is illustrated with selected examples of recent experimental and computational studies pursued synergistically in the investigation of secondary active transporters and GPCRs. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID:26806157

  3. Molecular Characterization of Transgenic Events Using Next Generation Sequencing Approach.

    PubMed

    Guttikonda, Satish K; Marri, Pradeep; Mammadov, Jafar; Ye, Liang; Soe, Khaing; Richey, Kimberly; Cruse, James; Zhuang, Meibao; Gao, Zhifang; Evans, Clive; Rounsley, Steve; Kumpatla, Siva P

    2016-01-01

    Demand for the commercial use of genetically modified (GM) crops has been increasing in light of the projected growth of world population to nine billion by 2050. A prerequisite of paramount importance for regulatory submissions is the rigorous safety assessment of GM crops. One of the components of safety assessment is molecular characterization at DNA level which helps to determine the copy number, integrity and stability of a transgene; characterize the integration site within a host genome; and confirm the absence of vector DNA. Historically, molecular characterization has been carried out using Southern blot analysis coupled with Sanger sequencing. While this is a robust approach to characterize the transgenic crops, it is both time- and resource-consuming. The emergence of next-generation sequencing (NGS) technologies has provided highly sensitive and cost- and labor-effective alternative for molecular characterization compared to traditional Southern blot analysis. Herein, we have demonstrated the successful application of both whole genome sequencing and target capture sequencing approaches for the characterization of single and stacked transgenic events and compared the results and inferences with traditional method with respect to key criteria required for regulatory submissions. PMID:26908260

  4. 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.

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

    PubMed

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

    2016-01-01

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

  6. The continuous molecular fields approach to building 3D-QSAR models.

    PubMed

    Baskin, Igor I; Zhokhova, Nelly I

    2013-05-01

    The continuous molecular fields (CMF) approach is based on the application of continuous functions for the description of molecular fields instead of finite sets of molecular descriptors (such as interaction energies computed at grid nodes) commonly used for this purpose. These functions can be encapsulated into kernels and combined with kernel-based machine learning algorithms to provide a variety of novel methods for building classification and regression structure-activity models, visualizing chemical datasets and conducting virtual screening. In this article, the CMF approach is applied to building 3D-QSAR models for 8 datasets through the use of five types of molecular fields (the electrostatic, steric, hydrophobic, hydrogen-bond acceptor and donor ones), the linear convolution molecular kernel with the contribution of each atom approximated with a single isotropic Gaussian function, and the kernel ridge regression data analysis technique. It is shown that the CMF approach even in this simplest form provides either comparable or enhanced predictive performance in comparison with state-of-the-art 3D-QSAR methods. PMID:23719959

  7. Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach

    PubMed Central

    Bosquesi, Priscila Longhin; Melo, Thais Regina Ferreira; Vizioli, Ednir Oliveira; dos Santos, Jean Leandro; Chung, Man Chin

    2011-01-01

    The design of new drugs with better physiochemical properties, adequate absorption, distribution, metabolism, and excretion, effective pharmacologic potency and lacking toxicity remains is a challenge. Inflammation is the initial trigger of several different diseases, such as Alzheimer's disease, asthma, atherosclerosis, colitis, rheumatoid arthritis, depression, cancer; and disorders such as obesity and sexual dysfunction. Although inflammation is not the direct cause of these disorders, inflammatory processes often increase related pain and suffering. New anti-inflammatory drugs developed using molecular hybridization techniques to obtain multiple-ligand drugs can act at one or multiple targets, allowing for synergic action and minimizing toxicity. This work is a review of new anti-inflammatory drugs developed using the molecular modification approach.

  8. Photoswitchable gel assembly based on molecular recognition.

    PubMed

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

    2012-01-01

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

  9. 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

  10. Approaches to uncovering cancer diagnostic and prognostic molecular signatures

    PubMed Central

    Hong, Shengjun; Huang, Yi; Cao, Yaqiang; Chen, Xingwei; Han, Jing-Dong J

    2014-01-01

    The recent rapid development of high-throughput technology enables the study of molecular signatures for cancer diagnosis and prognosis at multiple levels, from genomic and epigenomic to transcriptomic. These unbiased large-scale scans provide important insights into the detection of cancer-related signatures. In addition to single-layer signatures, such as gene expression and somatic mutations, integrating data from multiple heterogeneous platforms using a systematic approach has been proven to be particularly effective for the identification of classification markers. This approach not only helps to uncover essential driver genes and pathways in the cancer network that are responsible for the mechanisms of cancer development, but will also lead us closer to the ultimate goal of personalized cancer therapy. PMID:27308330

  11. Hybrid Metaheuristic Approach for Nonlocal Optimization of Molecular Systems.

    PubMed

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

    2013-04-01

    Accurate modeling of molecular systems requires a good knowledge of the structure; therefore, conformation searching/optimization is a routine necessity in computational chemistry. Here we present a hybrid metaheuristic optimization (HMO) algorithm, which combines ant colony optimization (ACO) and particle swarm optimization (PSO) for the optimization of molecular systems. The HMO implementation meta-optimizes the parameters of the ACO algorithm on-the-fly by the coupled PSO algorithm. The ACO parameters were optimized on a set of small difluorinated polyenes where the parameters exhibited small variance as the size of the molecule increased. The HMO algorithm was validated by searching for the closed form of around 100 molecular balances. Compared to the gradient-based optimized molecular balance structures, the HMO algorithm was able to find low-energy conformations with a 87% success rate. Finally, the computational effort for generating low-energy conformation(s) for the phenylalanyl-glycyl-glycine tripeptide was approximately 60 CPU hours with the ACO algorithm, in comparison to 4 CPU years required for an exhaustive brute-force calculation. PMID:26583559

  12. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    PubMed Central

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

  13. Prediction of reactive hazards based on molecular structure.

    PubMed

    Saraf, S R; Rogers, W J; Mannan, M S

    2003-03-17

    There is considerable interest in prediction of reactive hazards based on chemical structure. Calorimetric measurements to determine reactivity can be resource consuming, so computational methods to predict reactivity hazards present an attractive option. This paper reviews some of the commonly employed theoretical hazard evaluation techniques, including the oxygen-balance method, ASTM CHETAH, and calculated adiabatic reaction temperature (CART). It also discusses the development of a study table to correlate and predict calorimetric properties of pure compounds. Quantitative structure-property relationships (QSPR) based on quantum mechanical calculations can be employed to correlate calorimetrically measured onset temperatures, T(o), and energies of reaction, -deltaH, with molecular properties. To test the feasibility of this approach, the QSPR technique is used to correlate differential scanning calorimeter (DSC) data, T(o) and -deltaH, with molecular properties for 19 nitro compounds. PMID:12628775

  14. 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. PMID:25404035

  15. Materiality in a Practice-Based Approach

    ERIC Educational Resources Information Center

    Svabo, Connie

    2009-01-01

    Purpose: The paper aims to provide an overview of the vocabulary for materiality which is used by practice-based approaches to organizational knowing. Design/methodology/approach: The overview is theoretically generated and is based on the anthology Knowing in Organizations: A Practice-based Approach edited by Nicolini, Gherardi and Yanow. The…

  16. A machine learning approach to computer-aided molecular design.

    PubMed

    Bolis, G; Di Pace, L; Fabrocini, F

    1991-12-01

    Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one--the specialization step--the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase--the generalization step--the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process. PMID:1818094

  17. Molecular allergology approach to allergic diseases in the paediatric age

    PubMed Central

    Alessandri, Claudia; Zennaro, Danila; Zaffiro, Alessandra; Mari, Adriano

    2009-01-01

    Identification, characterization, and purification of allergens are essential for the structural and immunologic studies needed to understand how these molecules induce specific IgE antibody production by the human immune system. Advances in molecular biology techniques have led to the production of recombinant allergens having constant properties, allowing detection of specific IgE directed against different molecular components of an allergenic source. Presence of homologous allergens in different sources is the reason for cross-reaction. Molecule-based diagnostic tools can lead to better interpretation of poly-sensitizations, observed by ST and in vitro tests using allergenic extracts as they were made before. Some examples IgE sensitization to major genuine allergens and panallergens will be presented. PMID:19804642

  18. Clarifying Prehistoric Parasitism from a Complementary Morphological and Molecular Approach.

    PubMed

    Cleeland, Lauren M; Reichard, Mason V; Tito, Raul Y; Reinhard, Karl J; Lewis, Cecil M

    2013-07-01

    This paper reports an approach to the identification of prehistoric parasitic infection, which integrates traditional morphological methods with molecular methods. The approach includes the strengths of each method while mitigating the limitations. Demonstrating the efficacy of this approach, we provide a case study from a 1,400 year old desiccated fecal sample from La Cueva de los Muertos Chiquitos, archaeological site, near Rio Zape, Durango, Mexico. Traditionally prepared microscope slides were processed via microscopy and tentative ascarids were identified. Information regarding the parasites' developmental stage was recorded. DNA was then extracted directly from the slide material. From this DNA extract, a small segment of the 18S ribosomal RNA gene variant that is specific to Ascaris, and its phylogenetically close relatives, was targeted for PCR amplification and sequencing. Phylogenetic analysis of the DNA sequence best matched a member of physalopterids, rather than ascarids, with a single exception of a match to Contracaecum spiculigerum. Subsequent extractions, amplifications and sequencing of the original rehydrated coprolite material confirmed these results. The C. spiculigerum sequence represented a phylogenetic anomaly and subsequent analysis determined the sequence was an error in the BLAST database, likely attributable to misidentification of juvenile specimens prior to sequencing and submission. Physaloptera are a difficult genus to identify morphologically and can carry major health burdens. They may be underreported in humans, in part, because of morphological similarities to the more common human parasites belonging to ascarids. We conclude that integrating traditional morphological methods with molecular methods can help resolve this issue, in both contemporary and prehistoric populations. PMID:23645967

  19. Clarifying Prehistoric Parasitism from a Complementary Morphological and Molecular Approach

    PubMed Central

    Cleeland, Lauren M.; Reichard, Mason V.; Tito, Raul Y.; Reinhard, Karl J.; Lewis, Cecil M.

    2013-01-01

    This paper reports an approach to the identification of prehistoric parasitic infection, which integrates traditional morphological methods with molecular methods. The approach includes the strengths of each method while mitigating the limitations. Demonstrating the efficacy of this approach, we provide a case study from a 1,400 year old desiccated fecal sample from La Cueva de los Muertos Chiquitos, archaeological site, near Rio Zape, Durango, Mexico. Traditionally prepared microscope slides were processed via microscopy and tentative ascarids were identified. Information regarding the parasites’ developmental stage was recorded. DNA was then extracted directly from the slide material. From this DNA extract, a small segment of the 18S ribosomal RNA gene variant that is specific to Ascaris, and its phylogenetically close relatives, was targeted for PCR amplification and sequencing. Phylogenetic analysis of the DNA sequence best matched a member of physalopterids, rather than ascarids, with a single exception of a match to Contracaecum spiculigerum. Subsequent extractions, amplifications and sequencing of the original rehydrated coprolite material confirmed these results. The C. spiculigerum sequence represented a phylogenetic anomaly and subsequent analysis determined the sequence was an error in the BLAST database, likely attributable to misidentification of juvenile specimens prior to sequencing and submission. Physaloptera are a difficult genus to identify morphologically and can carry major health burdens. They may be underreported in humans, in part, because of morphological similarities to the more common human parasites belonging to ascarids. We conclude that integrating traditional morphological methods with molecular methods can help resolve this issue, in both contemporary and prehistoric populations. PMID:23645967

  20. Molecular diagnostics: future probe-based strategies.

    PubMed

    Marsh, Peter; Cardy, Donald L N

    2004-01-01

    Nucleic acid amplification technologies (NAATs) represent powerful tools in clinical microbiology, particularly in areas where traditional culture-based methods alone prove insufficient. A notable advantage is in reducing the time from taking samples to reporting results. This, and the specificity and sensitivity imparted by NAATs, can help to improve patient care. Both thermal and isothermal NAATs have been adapted to aid diagnosis in clinical laboratories. Current molecular diagnostic assays are generally high-tech, and are expensive to buy and perform. Easy-to-use NAATs are beginning to appear, not only facilitating acceptable throughput in clinical laboratories, but also allowing tests to move out of the laboratory, closer to the point of care. Demand for simpler, miniaturized equipment and assays, and the trend toward personalized medicine, is leading towards the development of fully integrated automation and home-use kits. The integration of diverse disciplines, such as genomics, molecular biology, microelectromechanical systems, microfluidics, microfabrication, and organic chemistry, is behind the emerging DNA microarray technology. Development of DNA microchips allows the simultaneous detection of potentially thousands of target sequences, not only favoring high throughput, but also the potential for genotyping patient subsets with respect to their response to particular drug types (pharmakogenomics). It is envisaged that the future of probe-based technologies will see the development of fully integrated assays and devices suitable for nonskilled users. PMID:15148419

  1. Molecular cloning of protein-based polymers.

    PubMed

    Mi, Lixin

    2006-07-01

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

  2. A molecular chemical approach to the magnetic multilayers

    NASA Astrophysics Data System (ADS)

    Coronado, E.; Galán-Mascarós, J. R.; Gómez-García, C. J.; Burriel, R.

    1999-05-01

    Using the bi-dimensional bimetallic networks based upon oxalate complexes, it is possible to prepare new multilayered materials by insertion of 'electroactive' molecules in between these layers. According to this approach a new family of compounds presenting alternating ferromagnetic—paramagnetic layers have been successfully prepared. Here we present the magnetic and specific heat characterization.

  3. Molecular MRI approaches to the detection of CNS inflammation.

    PubMed

    Sibson, Nicola R; Anthony, Daniel C; van Kasteren, Sander; Dickens, Alex; Perez-Balderas, Francisco; McAteer, Martina A; Choudhury, Robin P; Davis, Benjamin G

    2011-01-01

    Inflammation is a key component of many neurological diseases, yet our understanding of the contribution of these processes to tissue damage remains poor. For many such diseases, magnetic resonance imaging (MRI) has become the method of choice for clinical diagnosis. However, many of the MRI parameters that enable disease detection, such as passive contrast enhancement across a compromised blood-brain barrier, are weighted towards late-stage disease. Moreover, whilst these methods may report on disease severity, they are not able to provide information on either disease activity or the underlying molecular processes. There is a need, therefore, to develop methods that enable earlier disease detection, potentially long before clinical symptoms become apparent, together with identification of specific molecular processes that may guide specific therapy. This chapter describes the methodology for the synthesis and validation of two novel, functional MRI-detectable probes, based on microparticles of iron oxide (MPIO), which target endothelial adhesion molecules. These contrast agents enable the detection of acute brain inflammation in vivo, at a time when pathology is undetectable by conventional MRI. Such molecular MRI methods are opening new vistas for the acute diagnosis of CNS disease, together with the possibility for individually tailored therapy and earlier, more sensitive assessment of the efficacy of novel therapies. PMID:21279613

  4. Molecular Modeling Approaches to Study the Binding Mode on Tubulin of Microtubule Destabilizing and Stabilizing Agents

    NASA Astrophysics Data System (ADS)

    Botta, Maurizio; Forli, Stefano; Magnani, Matteo; Manetti, Fabrizio

    Tubulin targeting agents constitute an important class of anticancer drugs. By acting either as microtubule stabilizers or destabilizers, they disrupt microtubule dynamics, thus inducing mitotic arrest and, ultimately, cell death by apoptosis. Three different binding sites, whose exact location on tubulin has been experimentally detected, have been identified so far for antimitotic compound targeting microtubules, namely the taxoid, the colchicine and the vinka alkaloid binding site. A number of ligand- and structure-based molecular modeling studies in this field has been reported over the years, aimed at elucidating the binding modes of both stabilizing and destabilizing agent, as well as the molecular features responsible for their efficacious interaction with tubulin. Such studies are described in this review, focusing on information provided by different modeling approaches on the structural determinants of antitubulin agents and the interactions with the binding pockets on tubulin emerged as fundamental for antitumor activity.To describe molecular modeling approaches applied to date to molecules known to bind microtubules, this paper has been divided into two main parts: microtubule destabilizing (Part 1) and stabilizing (Part 2) agents. The first part includes structure-based and ligand-based approaches to study molecules targeting colchicine (1.1) and vinca alkaloid (1.2) binding sites, respectively. In the second part, the studies performed on microtubule-stabilizing antimitotic agents (MSAA) are described. Starting from the first representative compound of this class, paclitaxel, molecular modeling studies (quantitative structure-activity relationships - QSAR - and structure-based approaches), performed on natural compounds acting with the same mechanism of action and temptative common pharmacophoric hypotheses for all of these compounds, are reported.

  5. Molecular approaches to enhance surveillance of gonococcal antimicrobial resistance.

    PubMed

    Goire, Namraj; Lahra, Monica M; Chen, Marcus; Donovan, Basil; Fairley, Christopher K; Guy, Rebecca; Kaldor, John; Regan, David; Ward, James; Nissen, Michael D; Sloots, Theo P; Whiley, David M

    2014-03-01

    The best available data indicate that the world is heading towards a pandemic of extensively drug-resistant Neisseria gonorrhoeae. At the same time, clinical microbiology laboratories have moved away from using culture-based methods to diagnose gonorrhoea, thus undermining our ability to detect antimicrobial resistance (AMR) using current technologies. In this Opinion article, we discuss the problem of N. gonorrhoeae AMR, particularly emerging resistance to the cephalosporin ceftriaxone, outline current concerns about the surveillance of N. gonorrhoeae AMR and propose the use of molecular methods on a large scale to systematically enhance surveillance. PMID:24509781

  6. Molecular and genetic ecotoxicologic approaches to aquatic environmental bioreporting.

    PubMed Central

    Beaty, B J; Black, W C; Carlson, J O; Clements, W H; DuTeau, N; Harrahy, E; Nuckols, J; Kenneth, E; Olson, K E; Rayms-Keller, A

    1998-01-01

    Molecular and population genetic ecotoxicologic approaches are being developed for the utilization of arthropods as bioreporters of heavy metal mixtures in the environment. The explosion of knowledge in molecular biology, molecular genetics, and biotechnology provides an unparalleled opportunity to use arthropods as bioreporter organisms. Interspecific differences in aquatic arthropod populations have been previously demonstrated in response to heavy metal insult in the Arkansas River (AR) California Gulch Superfund site (CGSS). Population genetic analyses were conducted on the mayfly Baetis tricaudatus. Genetic polymorphisms were detected in polymerase chain reaction amplified 16S mitochondrial rDNA (a selectively neutral gene) of B tricaudatus using single-strand conformation polymorphism analysis. Genetic differences may have resulted from impediments to gene flow in the population caused by mortality arising from exposure to heavy metal mixture pollution. In laboratory studies a candidate metal-responsive mucinlike gene, which is metal and dose specific, has been identified in Chironomus tentans and other potential AR-CGSS bioreporter species. Population genetic analyses using the mucinlike gene may provide insight into the role of this selectable gene in determining the breeding structure of B. tricaudatus in the AR-CGSS and may provide mechanistic insight into determinants of aquatic arthropod response to heavy metal insult. Metal-responsive (MR) genes and regulatory sequences are being isolated, characterized, and assayed for differential gene expression in response to heavy metal mixture pollution in the AR-CGSS. Identified promoter sequences can then be engineered into previously developed MR constructs to provide sensitive in vitro assays for environmental bioreporting of heavy metal mixtures. The results of the population genetic studies are being entered into an AR geographic information system that contains substantial biological, chemical, and

  7. Recent molecular approaches to understanding astrocyte function in vivo

    PubMed Central

    Davila, David; Thibault, Karine; Fiacco, Todd A.; Agulhon, Cendra

    2013-01-01

    Astrocytes are a predominant glial cell type in the nervous systems, and are becoming recognized as important mediators of normal brain function as well as neurodevelopmental, neurological, and neurodegenerative brain diseases. Although numerous potential mechanisms have been proposed to explain the role of astrocytes in the normal and diseased brain, research into the physiological relevance of these mechanisms in vivo is just beginning. In this review, we will summarize recent developments in innovative and powerful molecular approaches, including knockout mouse models, transgenic mouse models, and astrocyte-targeted gene transfer/expression, which have led to advances in understanding astrocyte biology in vivo that were heretofore inaccessible to experimentation. We will examine the recently improved understanding of the roles of astrocytes – with an emphasis on astrocyte signaling – in the context of both the healthy and diseased brain, discuss areas where the role of astrocytes remains debated, and suggest new research directions. PMID:24399932

  8. Rapid Molecular Identification of Human Taeniid Cestodes by Pyrosequencing Approach

    PubMed Central

    Thanchomnang, Tongjit; Tantrawatpan, Chairat; Intapan, Pewpan M.; Sanpool, Oranuch; Janwan, Penchom; Lulitanond, Viraphong; Tourtip, Somjintana; Yamasaki, Hiroshi; Maleewong, Wanchai

    2014-01-01

    Taenia saginata, T. solium, and T. asiatica are causative agents of taeniasis in humans. The difficulty of morphological identification of human taeniids can lead to misdiagnosis or confusion. To overcome this problem, several molecular methods have been developed, but use of these tends to be time-consuming. Here, a rapid and high-throughput pyrosequencing approach was developed for the identification of three human taeniids originating from various countries. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the three Taenia species were designed. Variations in a 26-nucleotide target region were used for identification. The reproducibility and accuracy of the pyrosequencing technology was confirmed by Sanger sequencing. This technique will be a valuable tool to distinguish between sympatric human taeniids that occur in Thailand, Asia and Pacific countries. This method could potentially be used for the molecular identification of the taeniid species that might be associated with suspicious cysts and lesions, or cyst residues in humans or livestock at the slaughterhouse. PMID:24945530

  9. Rapid molecular identification of human taeniid cestodes by pyrosequencing approach.

    PubMed

    Thanchomnang, Tongjit; Tantrawatpan, Chairat; Intapan, Pewpan M; Sanpool, Oranuch; Janwan, Penchom; Lulitanond, Viraphong; Tourtip, Somjintana; Yamasaki, Hiroshi; Maleewong, Wanchai

    2014-01-01

    Taenia saginata, T. solium, and T. asiatica are causative agents of taeniasis in humans. The difficulty of morphological identification of human taeniids can lead to misdiagnosis or confusion. To overcome this problem, several molecular methods have been developed, but use of these tends to be time-consuming. Here, a rapid and high-throughput pyrosequencing approach was developed for the identification of three human taeniids originating from various countries. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the three Taenia species were designed. Variations in a 26-nucleotide target region were used for identification. The reproducibility and accuracy of the pyrosequencing technology was confirmed by Sanger sequencing. This technique will be a valuable tool to distinguish between sympatric human taeniids that occur in Thailand, Asia and Pacific countries. This method could potentially be used for the molecular identification of the taeniid species that might be associated with suspicious cysts and lesions, or cyst residues in humans or livestock at the slaughterhouse. PMID:24945530

  10. Chemoinformatics Approach for Building Molecular Networks from Marine Organisms.

    PubMed

    Karthikeyan, Muthukumarasamy; Nimje, Deepika; Pahujani, Rakhi; Tyagi, Kushal; Bapat, Sanket; Vyas, Renu; Pillai Padmakumar, Krishna

    2015-01-01

    Natural products obtained from marine sources are considered to be a rich and diverse source of potential drugs. In the present work we demonstrate the use of chemoinformatics approach for the design of new molecules inspired by molecules from marine organisms. Accordingly we have assimilated information from two major scientific domains namely chemoinformatics and biodiversity informatics to develop an interactive marine database named MIMMO (Medicinally Important Molecules from Marine Organisms). The database can be queried for species, molecules, scaffolds, drugs, diseases and associated cumulative biological activity spectrum along with links to the literature resources. Molecular informatics analysis of the molecules obtained from MIMMO was performed to study their chemical space. The distinct skeletal features of the biologically active compounds isolated from marine species were identified. Scaffold molecules and species networks were created to identify common scaffolds from marine source and drug space. An analysis of the entire molecular data revealed a unique list of around 2000 molecules from which ten most frequently occurring distinct scaffolds were obtained. PMID:26138570

  11. 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. PMID:25703726

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

    PubMed

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

    2010-12-01

    In this study, we applied DNA barcoding to identify species using short DNA sequence analysis. We examined the utility of DNA barcoding by identifying 53 Korean freshwater fish species, 233 other freshwater fish species, and 1339 saltwater fish species. We successfully developed a web-based molecular identification system for fish (MISF) using a profile hidden Markov model. MISF facilitates efficient and reliable species identification, overcoming the limitations of conventional taxonomic approaches. MISF is freely accessible at http://bioinfosys.snu.ac.kr:8080/MISF/misf.jsp . PMID:21110132

  13. A novel approach for determining the minimum feed in nanochannels processing via molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Ren, Jiaqi; Dong, Zeguang; Zhao, Jinsheng; Liu, Pinkuan

    2016-04-01

    A novel approach based on molecular dynamics (MD) simulation has been proposed for the first time with the focus on quantifying the minimum feed (MF) in atomic force microscope (AFM) based nanochannel fabrication. This approach involves a coarse-to-fine criterion to determine MF so that regular nanochannel patterns can be obtained. The method is first introduced step by step and then confirmatory test is performed to demonstrate the capability of this contour-based method. MF judging studies are also performed systematically in which they vary in the aspects of scratching depth, tip angles, and tip shapes. Dislocations generation, surface quality, and scratching forces in the initial and subsequent scratches are investigated in detail. This method can overcome the drawbacks of high cost and low efficiency in experimental studies. Furthermore, our method sheds light on the manufacturing technique of nanochannels, which can help to obtain the surface morphologies with higher quality than traditional approaches.

  14. 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

  15. Molecular Bases of Corneal Endothelial Dystrophies

    PubMed Central

    Schmedt, Thore; Silva, Mariana Mazzini; Ziaei, Alireza; Jurkunas, Ula

    2011-01-01

    The phrase “corneal endothelial dystrophies” embraces a group of bilateral corneal conditions that are characterized by a non-inflammatory and progressive degradation of corneal endothelium. Corneal endothelial cells exhibit a high pump site density and, along with barrier function, are responsible for maintaining the cornea in its natural state of relative dehydration. Gradual loss of endothelial cells leads to an insufficient water outflow, resulting in corneal edema and loss of vision. Since the pathologic mechanisms remain largely unknown, the only current treatment option is surgical transplantation when vision is severely impaired. In the past decade, important steps have been taken to understand how endothelial degeneration progresses on the molecular level. Studies of affected multigenerational families and sporadic cases identified genes and chromosomal loci, and revealed either Mendelian or complex disorder inheritance patterns. Mutations have been detected in genes that carry important structural, metabolic, cytoprotective, and regulatory functions in corneal endothelium. In addition to genetic predisposition, environmental factors like oxidative stress were found to be involved in the pathogenesis of endotheliopathies. This review summarizes and crosslinks the recent progress on deciphering the molecular bases of corneal endothelial dystrophies. PMID:21855542

  16. Dissecting plasmodesmata molecular composition by mass spectrometry-based proteomics

    PubMed Central

    Salmon, Magali S.; Bayer, Emmanuelle M. F.

    2013-01-01

    In plants, the intercellular communication through the membranous channels called plasmodesmata (PD; singular plasmodesma) plays pivotal roles in the orchestration of development, defence responses, and viral propagation. PD are dynamic structures embedded in the plant cell wall that are defined by specialized domains of the endoplasmic reticulum (ER) and the plasma membrane (PM). PD structure and unique functions are guaranteed by their particular molecular composition. Yet, up to recent years and despite numerous approaches such as mutant screens, immunolocalization, or screening of random cDNAs, only few PD proteins had been conclusively identified and characterized. A clear breakthrough in the search of PD constituents came from mass-spectrometry-based proteomic approaches coupled with subcellular fractionation strategies. Due to their position, firmly anchored in the extracellular matrix, PD are notoriously difficult to isolate for biochemical analysis. Proteomic-based approaches have therefore first relied on the use of cell wall fractions containing embedded PD then on “free” PD fractions whereby PD membranes were released from the walls by enzymatic degradation. To discriminate between likely contaminants and PD protein candidates, bioinformatics tools have often been used in combination with proteomic approaches. GFP fusion proteins of selected candidates have confirmed the PD association of several protein families. Here we review the accomplishments and limitations of the proteomic-based strategies to unravel the functional and structural complexity of PD. We also discuss the role of the identified PD-associated proteins. PMID:23335932

  17. An analytical molecular orbital approach in tetrathiafulvalene tetracyanoquinodimethane (TTF-TCNQ)

    NASA Astrophysics Data System (ADS)

    Tada, Tomofumi; Aoki, Yuriko; Imamura, Akira

    In low-dimensional molecular crystals exhibiting the Peierls instability, intercolumnar interactions play an important role in electrical conduction. In this work, we propose an efficient method based on molecular orbital theory for studying the Peierls instability in molecular crystals composed of mixed-valence complexes. A perturbational approach to general N-merized systems is incorporated and applied to tetrathiafulvalene tetracyanoquinodimethane (TTF-TCNQ) crystals. From the results of the calculations, a mixed state of several commensurate distortions is proposed as another aspect of the incommensurate distortion in TTF-TCNQ under atmospheric pressure, and TTF+0.5-TCNQ-0.5 crystal is found to be expected as an electronic conductor under high pressure.

  18. Molecular subtyping of breast cancer: opportunities for new therapeutic approaches.

    PubMed

    Mullan, P B; Millikan, R C

    2007-12-01

    Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from unnecessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basal-like breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives. (Part of a Multi-author Review). PMID:17957336

  19. Ab initio molecular dynamics with noisy forces: Validating the quantum Monte Carlo approach with benchmark calculations of molecular vibrational properties

    SciTech Connect

    Luo, Ye Sorella, Sandro; Zen, Andrea

    2014-11-21

    We present a systematic study of a recently developed ab initio simulation scheme based on molecular dynamics and quantum Monte Carlo. In this approach, a damped Langevin molecular dynamics is employed by using a statistical evaluation of the forces acting on each atom by means of quantum Monte Carlo. This allows the use of an highly correlated wave function parametrized by several variational parameters and describing quite accurately the Born-Oppenheimer energy surface, as long as these parameters are determined at the minimum energy condition. However, in a statistical method both the minimization method and the evaluation of the atomic forces are affected by the statistical noise. In this work, we study systematically the accuracy and reliability of this scheme by targeting the vibrational frequencies of simple molecules such as the water monomer, hydrogen sulfide, sulfur dioxide, ammonia, and phosphine. We show that all sources of systematic errors can be controlled and reliable frequencies can be obtained with a reasonable computational effort. This work provides convincing evidence that this molecular dynamics scheme can be safely applied also to realistic systems containing several atoms.

  20. A computational kinematics and evolutionary approach to model molecular flexibility for bionanotechnology

    NASA Astrophysics Data System (ADS)

    Brintaki, Athina N.

    Modeling molecular structures is critical for understanding the principles that govern the behavior of molecules and for facilitating the exploration of potential pharmaceutical drugs and nanoscale designs. Biological molecules are flexible bodies that can adopt many different shapes (or conformations) until they reach a stable molecular state that is usually described by the minimum internal energy. A major challenge in modeling flexible molecules is the exponential explosion in computational complexity as the molecular size increases and many degrees of freedom are considered to represent the molecules' flexibility. This research work proposes a novel generic computational geometric approach called enhanced BioGeoFilter (g.eBGF) that geometrically interprets inter-atomic interactions to impose geometric constraints during molecular conformational search to reduce the time for identifying chemically-feasible conformations. Two new methods called Kinematics-Based Differential Evolution ( kDE) and Biological Differential Evolution ( BioDE) are also introduced to direct the molecular conformational search towards low energy (stable) conformations. The proposed kDE method kinematically describes a molecule's deformation mechanism while it uses differential evolution to minimize the intra-molecular energy. On the other hand, the proposed BioDE utilizes our developed g.eBGF data structure as a surrogate approximation model to reduce the number of exact evaluations and to speed the molecular conformational search. This research work will be extremely useful in enabling the modeling of flexible molecules and in facilitating the exploration of nanoscale designs through the virtual assembly of molecules. Our research work can also be used in areas such as molecular docking, protein folding, and nanoscale computer-aided design where rapid collision detection scheme for highly deformable objects is essential.

  1. Molecular solution approach to synthesize electronic quality Cu2ZnSnS4 thin films.

    PubMed

    Yang, Wenbing; Duan, Hsin-Sheng; Cha, Kitty C; Hsu, Chia-Jung; Hsu, Wan-Ching; Zhou, Huanping; Bob, Brion; Yang, Yang

    2013-05-01

    Successful implementation of molecular solution processing from a homogeneous and stable precursor would provide an alternative, robust approach to process multinary compounds compared with physical vapor deposition. Targeting deposition of chemically clear, high quality crystalline films requires specific molecular structure design and solvent selection. Hydrazine (N2H4) serves as a unique and powerful medium, particularly to incorporate selected metallic elements and chalcogens into a stable solution as metal chalcogenide complexes (MCC). However, not all the elements and compounds can be easily dissolved. In this manuscript, we demonstrate a paradigm to incorporate previously insoluble transitional-metal elements into molecular solution as metal-atom hydrazine/hydrazine derivative complexes (MHHD), as exemplified by dissolving of the zinc constituent as Zn(NH2NHCOO)2(N2H4)2. Investigation into the evolution of molecular structure reveals the hidden roadmap to significantly enrich the variety of building blocks for soluble molecule design. The new category of molecular structures not only set up a prototype to incorporate other elements of interest but also points the direction for other compatible solvent selection. As demonstrated from the molecular precursor combining Sn-/Cu-MCC and Zn-MHHD, an ultrathin film of copper zinc tin sulfide (CZTS) was deposited. Characterization of a transistor based on the CZTS channel layer shows electronic properties comparable to CuInSe2, confirming the robustness of this molecular solution processing and the prospect of earth abundant CZTS for next generation photovoltaic materials. This paradigm potentially outlines a universal pathway, from individual molecular design using selected chelated ligands and combination of building blocks in a simple and stable solution to fundamentally change the way multinary compounds are processed. PMID:23581974

  2. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches

    PubMed Central

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D.

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis. PMID:26306443

  3. Molecular and Cellular Approaches for Diversifying and Extending Optogenetics

    PubMed Central

    Ramakrishnan, Charu; Mattis, Joanna; Prakash, Rohit; Diester, Ilka; Goshen, Inbal; Thompson, Kimberly R.; Deisseroth, Karl

    2014-01-01

    SUMMARY Optogenetic technologies employ light to control biological processes within targeted cells in vivo with high temporal precision. Here, we show that application of molecular trafficking principles can expand the optogenetic repertoire along several long-sought dimensions. Subcellular and transcellular trafficking strategies now permit (1) optical regulation at the far-red/infrared border and extension of optogenetic control across the entire visible spectrum, (2) increased potency of optical inhibition without increased light power requirement (nanoampere-scale chloride-mediated photocurrents that maintain the light sensitivity and reversible, step-like kinetic stability of earlier tools), and (3) generalizable strategies for targeting cells based not only on genetic identity, but also on morphology and tissue topology, to allow versatile targeting when promoters are not known or in genetically intractable organisms. Together, these results illustrate use of cell-biological principles to enable expansion of the versatile fast optogenetic technologies suitable for intact-systems biology and behavior. PMID:20303157

  4. Orbital Energy Levels in Molecular Hydrogen. A Simple Approach.

    ERIC Educational Resources Information Center

    Willis, Christopher J.

    1988-01-01

    Described are the energetics involved in the formation of molecular hydrogen using concepts that should be familiar to students beginning the study of molecular orbital theory. Emphasized are experimental data on ionization energies. Included are two-electron atomic and molecular systems. (CW)

  5. Novel molecular approaches to cystic fibrosis gene therapy

    PubMed Central

    Lee, Tim W. R.; Matthews, David A.; Blair, G. Eric

    2005-01-01

    Gene therapy holds promise for the treatment of a range of inherited diseases, such as cystic fibrosis. However, efficient delivery and expression of the therapeutic transgene at levels sufficient to result in phenotypic correction of cystic fibrosis pulmonary disease has proved elusive. There are many reasons for this lack of progress, both macroscopically in terms of airway defence mechanisms and at the molecular level with regard to effective cDNA delivery. This review of approaches to cystic fibrosis gene therapy covers these areas in detail and highlights recent progress in the field. For gene therapy to be effective in patients with cystic fibrosis, the cDNA encoding the cystic fibrosis transmembrane conductance regulator protein must be delivered effectively to the nucleus of the epithelial cells lining the bronchial tree within the lungs. Expression of the transgene must be maintained at adequate levels for the lifetime of the patient, either by repeat dosage of the vector or by targeting airway stem cells. Clinical trials of gene therapy for cystic fibrosis have demonstrated proof of principle, but gene expression has been limited to 30 days at best. Results suggest that viral vectors such as adenovirus and adeno-associated virus are unsuited to repeat dosing, as the immune response reduces the effectiveness of each subsequent dose. Nonviral approaches, such as cationic liposomes, appear more suited to repeat dosing, but have been less effective. Current work regarding non-viral gene delivery is now focused on understanding the mechanisms involved in cell entry, endosomal escape and nuclear import of the transgene. There is now increasing evidence to suggest that additional ligands that facilitate endosomal escape or contain a nuclear localization signal may enhance liposome-mediated gene delivery. Much progress in this area has been informed by advances in our understanding of the mechanisms by which viruses deliver their genomes to the nuclei of host

  6. Atopic dermatitis: molecular mechanisms, clinical aspects and new therapeutical approaches.

    PubMed

    Galli, E; Cicconi, R; Rossi, P; Casati, A; Brunetti, E; Mancino, G

    2003-03-01

    Atopic dermatitis (AD) is a genetically determinated, chronic inflammatory skin disorder associated with cutaneous erythema and severe pruritus, affecting 10-15% of children with increasing incidence and socio-economical relevance. Frequently, AD is associated with development of allergic rhinitis and/or asthma later in childhood. In most of patients AD is associated with a sensitization to food and/or environmental allergens and increased serum-IgE, while only a fewer percentage missed links to the classical atopic diathesis. Currently investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses, altered prostaglandin metabolism, intrinsic defects in the keratinocyte function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen presentation by epidermal dendritic cells. An inflammatory response of the two-phase-type and the effects of staphylococcal superantigens (SAgs) are also reported. At present a standardized cure of AD and a consensus on therapeutical approach of the severe form of the disease have not been established. Current management of AD is directed to the reduction of cutaneous inflammation and infection, mainly by S. aureus, and to the elimination of exacerbating factors (irritants, allergens, emotional stresses). Since patient with AD show abnormalities in immunoregulation, therapy directed to adjustment of their immune function could represent an alternative approach, particularly in the severe form of the disease. In this review, we analyse the clinical and genetic aspects of AD, the related molecular mechanisms, and the immunobiology of the disease, focusing our attention on current treatments and future perspectives on this topic. PMID:12630559

  7. Vibrational infrared and Raman spectra of polypeptides: Fragments-in-fragments within molecular tailoring approach.

    PubMed

    Sahu, Nityananda; Gadre, Shridhar R

    2016-03-21

    The present work reports the calculation of vibrational infrared (IR) and Raman spectra of large molecular systems employing molecular tailoring approach (MTA). Further, it extends the grafting procedure for the accurate evaluation of IR and Raman spectra of large molecular systems, employing a new methodology termed as Fragments-in-Fragments (FIF), within MTA. Unlike the previous MTA-based studies, the accurate estimation of the requisite molecular properties is achieved without performing any full calculations (FC). The basic idea of the grafting procedure is implemented by invoking the nearly basis-set-independent nature of the MTA-based error vis-à-vis the respective FCs. FIF has been tested out for the estimation of the above molecular properties for three isomers, viz., β-strand, 310- and α-helix of acetyl(alanine)nNH2 (n = 10, 15) polypeptides, three conformers of doubly protonated gramicidin S decapeptide and trpzip2 protein (PDB id: 1LE1), respectively, employing BP86/TZVP, M06/6-311G**, and M05-2X/6-31G** levels of theory. For most of the cases, a maximum difference of 3 cm(-1) is achieved between the grafted-MTA frequencies and the corresponding FC values. Further, a comparison of the BP86/TZVP level IR and Raman spectra of α-helical (alanine)20 and its N-deuterated derivative shows an excellent agreement with the existing experimental spectra. In view of the requirement of only MTA-based calculations and the ability of FIF to work at any level of theory, the current methodology provides a cost-effective solution for obtaining accurate spectra of large molecular systems. PMID:27004868

  8. Vibrational infrared and Raman spectra of polypeptides: Fragments-in-fragments within molecular tailoring approach

    NASA Astrophysics Data System (ADS)

    Sahu, Nityananda; Gadre, Shridhar R.

    2016-03-01

    The present work reports the calculation of vibrational infrared (IR) and Raman spectra of large molecular systems employing molecular tailoring approach (MTA). Further, it extends the grafting procedure for the accurate evaluation of IR and Raman spectra of large molecular systems, employing a new methodology termed as Fragments-in-Fragments (FIF), within MTA. Unlike the previous MTA-based studies, the accurate estimation of the requisite molecular properties is achieved without performing any full calculations (FC). The basic idea of the grafting procedure is implemented by invoking the nearly basis-set-independent nature of the MTA-based error vis-à-vis the respective FCs. FIF has been tested out for the estimation of the above molecular properties for three isomers, viz., β-strand, 310- and α-helix of acetyl(alanine)nNH2 (n = 10, 15) polypeptides, three conformers of doubly protonated gramicidin S decapeptide and trpzip2 protein (PDB id: 1LE1), respectively, employing BP86/TZVP, M06/6-311G**, and M05-2X/6-31G** levels of theory. For most of the cases, a maximum difference of 3 cm-1 is achieved between the grafted-MTA frequencies and the corresponding FC values. Further, a comparison of the BP86/TZVP level IR and Raman spectra of α-helical (alanine)20 and its N-deuterated derivative shows an excellent agreement with the existing experimental spectra. In view of the requirement of only MTA-based calculations and the ability of FIF to work at any level of theory, the current methodology provides a cost-effective solution for obtaining accurate spectra of large molecular systems.

  9. Cluster and Shell Structures in the Fermionic Molecular Dynamics Approach

    NASA Astrophysics Data System (ADS)

    Neff, Thomas; Feldmeier, Hans

    Nuclei in the p- and sd-shell are studied within the Fermionic Molecular Dynamics (FMD) model that uses Gaussian wave packets as single-particle states. Intrinsic many-body basis states are given by Slater determinants which have to be projected on parity, angular momentum and total linear momentum to restore the symmetries of the Hamiltonian. The flexibility of the Gaussian basis allows to economically describe states with shell structures as well as states featuring clustering or halos. The same effective interaction derived from the realistic Argonne V18 interaction in the Unitary Correlation Operator Method (UCOM) framework is used for all nuclei. We discuss the spectrum of 12C with a special emphasis on the structure of the first excited 0+ state, the famous Hoyle state. In the FMD approach the Hoyle state is found to be dominated by dilute α-cluster configurations. Recent measurements of the charge radii of Neon isotopes show an intriguing behaviour. This can be explained in FMD calculations by a structure change from 17Ne and 18Ne which can be essentially considered as an 15O or 16O core plus two protons in s2 or d2 configurations, respectively. For the heavier isotopes we find that the admixture of 3He and 4He cluster configurations in the ground states leads to much larger charge radii than obtained in a mean-field calculation.

  10. Comparative approaches in evolutionary psychology: molecular neuroscience meets the mind.

    PubMed

    Panksepp, Jaak; Moskal, Joseph R; Panksepp, Jules B; Kroes, Roger A

    2002-12-01

    Evolutionary psychologists often overlook a wealth of information existing between the proximate genotypic level and the ultimate phenotypic level. This commonly ignored level of biological organization is the ongoing activity of neurobiological systems. In this paper, we extend our previous arguments concerning strategic weaknesses of evolutionary psychology by advocating a foundational view that focuses on similarities in brain, behavior, and various basic psychological features across mammalian species. Such an approach offers the potential to link the emerging discipline of evolutionary psychology to its parent scientific disciplines such as biochemistry, physiology, molecular genetics, developmental biology and the neuroscientific analysis of animal behavior. We detail an example of this through our impending work using gene microarray technology to characterize gene expression patterns in rats during aggressive and playful social interactions. Through a focus on functional homologies and the experimental analysis of conserved, subcortical emotional and motivational brain systems, neuroevolutionary psychobiology can reveal ancient features of the human mind that are still shared with other animals. Claims regarding evolved, uniquely human, psychological constructs should be constrained by the rigorous evidentiary standards that are routine in other sciences. PMID:12496741

  11. Molecular Approaches to Understand Nutritional Potential of Coarse Cereals.

    PubMed

    Singh, Amit Kumar; Singh, Rakesh; Subramani, Rajkumar; Kumar, Rajesh; Wankhede, Dhammaprakash P

    2016-06-01

    Coarse grains are important group of crops that constitutes staple food for large population residing primarily in the arid and semi-arid regions of the world. Coarse grains are designated as nutri-cereals as they are rich in essential amino acids, minerals and vitamins. In spite of having several nutritional virtues in coarse grain as mentioned above, there is still scope for improvement in quality parameters such as cooking qualities, modulation of nutritional constituents and reduction or elimination of anti-nutritional factors. Besides its use in traditional cooking, coarse grains have been used mainly in the weaning food preparation and other malted food production. Improvement in quality parameters will certainly increase consumer's preference for coarse grains and increase their demand. The overall genetic gain in quality traits of economic importance in the cultivated varieties will enhance their industrial value and simultaneously increase income of farmers growing these varieties. The urgent step for improvement of quality traits in coarse grains requires a detailed understanding of molecular mechanisms responsible for varied level of different nutritional contents in different genotypes of these crops. In this review we have discussed the progresses made in understanding of coarse grain biology with various omics tool coupled with modern breeding approaches and the current status with regard to our effort towards dissecting traits related to improvement of quality and nutritional constituents of grains. PMID:27252585

  12. Single-cell approaches for molecular classification of endocrine tumors

    PubMed Central

    Koh, James; Allbritton, Nancy L.; Sosa, Julie A.

    2015-01-01

    Purpose of review In this review, we summarize recent developments in single-cell technologies that can be employed for the functional and molecular classification of endocrine cells in normal and neoplastic tissue. Recent findings The emergence of new platforms for the isolation, analysis, and dynamic assessment of individual cell identity and reactive behavior enables experimental deconstruction of intratumoral heterogeneity and other contexts, where variability in cell signaling and biochemical responsiveness inform biological function and clinical presentation. These tools are particularly appropriate for examining and classifying endocrine neoplasias, as the clinical sequelae of these tumors are often driven by disrupted hormonal responsiveness secondary to compromised cell signaling. Single-cell methods allow for multidimensional experimental designs incorporating both spatial and temporal parameters with the capacity to probe dynamic cell signaling behaviors and kinetic response patterns dependent upon sequential agonist challenge. Summary Intratumoral heterogeneity in the provenance, composition, and biological activity of different forms of endocrine neoplasia presents a significant challenge for prognostic assessment. Single-cell technologies provide an array of powerful new approaches uniquely well suited for dissecting complex endocrine tumors. Studies examining the relationship between clinical behavior and tumor compositional variations in cellular activity are now possible, providing new opportunities to deconstruct the underlying mechanisms of endocrine neoplasia. PMID:26632769

  13. Substrate Channel in Nitrogenase Revealed by a Molecular Dynamics Approach

    SciTech Connect

    Smith, Dayle; Danyal, Karamatullah; Raugei, Simone; Seefeldt, Lance C.

    2014-03-22

    Mo-dependent nitrogenase catalyzes the biological reduction of N2 to 2NH3 at the FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized sub-microsecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel not previously reported. The viability of the proposed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, with discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

  14. [Orbitozygomatic approaches to the skull base].

    PubMed

    Cherekaev, V A; Gol'bin, D A; Belov, A I; Radchenkov, N S; Lasunin, N V; Vinokurov, A G

    2015-01-01

    The paper is written in the lecture format and dedicated to one of the main basal approaches, the orbitozygomatic approach, that has been widely used by neurosurgeons for several decades. The authors describe the historical background of the approach development and the surgical technique features and also analyze the published data about application of the orbitozygomatic approach in surgery for skull base tumors and cerebral aneurysms. PMID:26529627

  15. Theoretical study of molecular vibrations in electron momentum spectroscopy experiments on furan: An analytical versus a molecular dynamical approach

    SciTech Connect

    Morini, Filippo; Deleuze, Michael S.; Watanabe, Noboru; Takahashi, Masahiko

    2015-03-07

    The influence of thermally induced nuclear dynamics (molecular vibrations) in the initial electronic ground state on the valence orbital momentum profiles of furan has been theoretically investigated using two different approaches. The first of these approaches employs the principles of Born-Oppenheimer molecular dynamics, whereas the so-called harmonic analytical quantum mechanical approach resorts to an analytical decomposition of contributions arising from quantized harmonic vibrational eigenstates. In spite of their intrinsic differences, the two approaches enable consistent insights into the electron momentum distributions inferred from new measurements employing electron momentum spectroscopy and an electron impact energy of 1.2 keV. Both approaches point out in particular an appreciable influence of a few specific molecular vibrations of A{sub 1} symmetry on the 9a{sub 1} momentum profile, which can be unravelled from considerations on the symmetry characteristics of orbitals and their energy spacing.

  16. Molecularly imprinted polymer based enantioselective sensing devices: a review.

    PubMed

    Tiwari, Mahavir Prasad; Prasad, Amrita

    2015-01-01

    Chiral recognition is the fundamental property of many biological molecules and is a quite important field in pharmaceutical analysis because of the pharmacologically different activities of enantiomers in living systems. Enantio-differentiating signal of the sensor requires specific interaction between the chiral compounds (one or a mixture of enantiomers) in question and the selector. This type of interaction is controlled normally by at least three binding centers, whose mutual arrangement and interacting characteristics with one of the enantiomers effectively control the selectivity of recognition. Molecular imprinting technology provides a unique opportunity for the creation of three-dimensional cavities with tailored recognition properties. Over the past decade, this field has expanded considerably across the variety of disciplines, leading to novel transduction approaches and many potential applications. The state-of-art of molecularly imprinted polymer-based chiral recognition might set an exotic trend toward the development of chiral sensors. The objective of this review is to provide comprehensive knowledge and information to all researchers who are interested in exploiting molecular imprinting technology toward the rational design of chiral sensors operating on different transduction principles, ranging from electrochemical to piezoelectric, being used for the detection of chiral compounds as they pose significant impact on the understanding of the origin of life and all processes that occur in living organisms. PMID:25467446

  17. 4-aminoquinoline based molecular hybrids as antimalarials: an overview.

    PubMed

    Manohar, Sunny; Tripathi, Mohit; Rawat, Diwan S

    2014-01-01

    In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance problems. Towards this end, a lot of effort has been put for generating 4-aminoquinoline based hybrid molecules as next generation antimalarial drugs effective in malarial chemotherapy. This short review deals about the recent advances carried in the field of 4-aminoquinoline based molecular hybrids as potential antimalarial agents. It also presents a brief and simplified story on the development of 4-aminoquinolines as a mainstay in malarial research programmes. PMID:25116580

  18. Quantum-chemical insight into structure-reactivity relationship in 4,5,6,7-tetrahalogeno-1H-benzimidazoles: a combined X-ray, DSC, DFT/QTAIM, Hirshfeld surface-based, and molecular docking approach.

    PubMed

    Latosińska, Jolanta Natalia; Latosińska, Magdalena; Maurin, Jan Krzysztof; Orzeszko, Andrzej; Kazimierczuk, Zygmunt

    2014-03-20

    The weak interaction patterns in 4,5,6,7-tetrahalogeno-1H-benzimidazoles, protein kinase CK2 inhibitors, in solid state are studied by the X-ray method and quantum chemistry calculations. The crystal structures of 4,5,6,7-tetrachloro- and 4,5,6,7-tetrabromo-1H-benzimidazole are determined by X-ray diffraction and refined to a final R-factor of 3.07 and 3.03%, respectively, at room temperature. The compound 4,5,6,7-tetrabromo-1H-benzimidazole, which crystallizes in the I41/a space group, is found to be isostructural with previously studied 4,5,6,7-tetraiodo-1H-benzimidazole in contrast to 4,5,6,7-tetrachloro-1H-benzimidazole, which crystallizes as triclinic P1̅ with 4 molecules in elementary unit. For 4,5,6,7-tetrachloro-1H-benzimidazole, differential scanning calorimetry (DSC) revealed a second order glassy phase transition at Tg = 95°/106° (heating/cooling), an indication of frozen disorder. The lack of 3D isostructurality found in all 4,5,6,7-tetrahalogeno-1H-benzimidazoles is elucidated on the basis of the intra- and intermolecular interactions (hydrogen bonding, van der Waals contacts, and C-H···π interactions). The topological Bader's Quantum Theory of Atoms in Molecules (QTAIM) and Spackman's Hirshfeld surface-based approaches reveal equilibration of electrostatic matching and dispersion van der Waals interactions between molecules consistent with the crystal site-symmetry. The weakening of van der Waals forces accompanied by increasing strength of the hydrogen bond (N-H···N) result in a decrease in the crystal site-symmetry and a change in molecular packing in the crystalline state. Crystal packing motifs were investigated with the aid of Hirshfeld surface fingerprint plots. The ordering 4,5,6,7-tetraiodo > 4,5,6,7-tetrabromo > 4,5,6,7-tetrachloro > 4,5,6,7-tetrafluoro reflects not only a decrease in crystal symmetry but also increase in chemical reactivity (electronic activation), which could explain some changes in biological activity of

  19. Light-powered, artificial molecular pumps: a minimalistic approach.

    PubMed

    Ragazzon, Giulio; Baroncini, Massimo; Silvi, Serena; Venturi, Margherita; Credi, Alberto

    2015-01-01

    The realization of artificial molecular motors capable of converting energy into mechanical work is a fascinating challenge of nanotechnology and requires reactive systems that can operate away from chemical equilibrium. This article describes the design and construction of a simple, supramolecular ensemble in which light irradiation causes the directional transit of a macrocycle along a nonsymmetric molecular axle, thus forming the basis for the development of artificial molecular pumps. PMID:26665081

  20. Light-powered, artificial molecular pumps: a minimalistic approach

    PubMed Central

    Ragazzon, Giulio; Baroncini, Massimo; Silvi, Serena; Venturi, Margherita

    2015-01-01

    Summary The realization of artificial molecular motors capable of converting energy into mechanical work is a fascinating challenge of nanotechnology and requires reactive systems that can operate away from chemical equilibrium. This article describes the design and construction of a simple, supramolecular ensemble in which light irradiation causes the directional transit of a macrocycle along a nonsymmetric molecular axle, thus forming the basis for the development of artificial molecular pumps. PMID:26665081

  1. [Molecular Approaches for the Diagnosis of Central Nervous System Infections].

    PubMed

    Ohkusu, Kiyofumi

    2015-07-01

    In recent years, molecular microbiology techniques have proven to be a useful supplement to conventional assays not only in identification of strains from culture, but also in direct detection of pathogens from clinical specimens. This review explores the application of molecular diagnostic techniques for infectious diseases in certain clinical contexts. It aims to assess how these molecular techniques can be integrated to enhance diagnostic capabilities for infectious diseases of the central nervous system. Finally, it emphasizes the need for close collaboration between physicians and clinical microbiologists when considering molecular diagnostics from unusual specimens/cases, because assays must be customized according to the clinical settings. PMID:26160810

  2. Molecular modelling on small molecular CDK2 inhibitors: an integrated approach using a combination of molecular docking, 3D-QSAR and pharmacophore modelling.

    PubMed

    Yuan, H; Liu, H; Tai, W; Wang, F; Zhang, Y; Yao, S; Ran, T; Lu, S; Ke, Z; Xiong, X; Xu, J; Chen, Y; Lu, T

    2013-10-01

    Cyclin-dependent kinase 2 (CDK2) has been identified as an important target for developing novel anticancer agents. Molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modelling were combined with the ultimate goal of studying the structure-activity relationship of CDK2 inhibitors. The comparative molecular similarity indices analysis (CoMSIA) model constructed based on a set of 3-aminopyrazole derivatives as CDK2 inhibitors gave statistically significant results (q (2) = 0.700; r (2) = 0.982). A HypoGen pharmacophore model, constructed using diverse CDK2 inhibitors, also showed significant statistics ([Formula: see text]Cost = 61.483; RMSD = 0.53; Correlation coefficient = 0.98). The small residues and error values between the estimated and experimental activities of the training and test set compounds proved their strong capability of activity prediction. The structural insights obtained from these two models were consistent with each other. The pharmacophore model summarized the important pharmacophoric features required for protein-ligand binding. The 3D contour maps in combination with the comprehensive pharmacophoric features helped to better interpret the structure-activity relationship. The results will be beneficial for the discovery and design of novel CDK2 inhibitors. The simplicity of this approach provides expansion to its applicability in optimizing other classes of small molecular CDK2 inhibitors. PMID:23941641

  3. [Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

    PubMed

    Tsuji, Daisuke

    2013-01-01

    Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal β-hexosaminidase α-subunits and β-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice. PMID:23370522

  4. Affinity based and molecularly imprinted cryogels: Applications in biomacromolecule purification.

    PubMed

    Andaç, Müge; Galaev, Igor Yu; Denizli, Adil

    2016-05-15

    The publications in macro-molecularly imprinted polymers have increased drastically in recent years with the development of water-based polymer systems. The macroporous structure of cryogels has allowed the use of these materials within different applications, particularly in affinity purification and molecular imprinting based methods. Due to their high selectivity, specificity, efficient mass transfer and good reproducibility, molecularly imprinted cryogels (MICs) have become attractive for researchers in the separation and purification of proteins. In this review, the recent developments in affinity based cryogels and molecularly imprinted cryogels in protein purification are reviewed comprehensively. PMID:26454622

  5. Fundamental Approaches in Molecular Biology for Communication Sciences and Disorders

    ERIC Educational Resources Information Center

    Bartlett, Rebecca S.; Jette, Marie E.; King, Suzanne N.; Schaser, Allison; Thibeault, Susan L.

    2012-01-01

    Purpose: This contemporary tutorial will introduce general principles of molecular biology, common deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein assays and their relevance in the field of communication sciences and disorders. Method: Over the past 2 decades, knowledge of the molecular pathophysiology of human disease has…

  6. Fundamental approaches in molecular biology for communication sciences and disorders

    PubMed Central

    Bartlett, Rebecca; Jetté, Marie E; King, Suzanne N.; Schaser, Allison; Thibeault, Susan L.

    2012-01-01

    Purpose This contemporary tutorial will introduce general principles of molecular biology, common DNA, RNA and protein assays and their relevance in the field of communication sciences and disorders (CSD). Methods Over the past two decades, knowledge of the molecular pathophysiology of human disease has increased at a remarkable pace. Most of this progress can be attributed to concomitant advances in basic molecular biology and, specifically, the development of an ever-expanding armamentarium of technologies for analysis of DNA, RNA and protein structure and function. Details of these methodologies, their limitations and examples from the CSD literature are presented. Results/Conclusions The use of molecular biology techniques in the fields of speech, language and hearing sciences is increasing, facilitating the need for an understanding of molecular biology fundamentals and common experimental assays. PMID:22232415

  7. Optical molecular imaging approach for rapid assessment of response of individual cancer cells to chemotherapy

    NASA Astrophysics Data System (ADS)

    Luo, Zhen; Tikekar, Rohan Vijay; Samadzadeh, Kiana Michelle; Nitin, Nitin

    2012-10-01

    Predicting the response of individual patients to cytotoxic chemotherapy drugs is critical for developing individualized therapies. With this motivation, an optical molecular imaging approach was developed to detect cisplatin induced changes in the uptake and intracellular retention of choline. Intracellular uptake of choline was characterized using a click chemistry reaction between propargyl choline and Alexa-488 azide. Cisplatin induced changes in the uptake of propargyl choline in cells and tumor spheroids were compared with similar measurements using a fluorescent analogue of deoxyglucose and conventional cell viability assays. Uptake and intracellular retention of propargyl choline decreased with an increase in concentration of cisplatin. Intracellular uptake of propargyl choline was significantly reduced within 3 h of incubation with a sub-lethal dose of cisplatin. Results demonstrate that the imaging approach based on propargyl choline was more sensitive in detecting the early response of cancer cells to cisplatin as compared to the imaging based on fluorescent analogue of deoxyglucose and cell viability assays. Imaging measurements in tumor spheroids show a significant decrease in the uptake of propargyl choline following treatment with cisplatin. Overall, the results demonstrate a novel optical molecular imaging approach for rapid measurement of the response of individual cancer cells to cisplatin treatment.

  8. Optical molecular imaging approach for rapid assessment of response of individual cancer cells to chemotherapy

    PubMed Central

    Luo, Zhen; Tikekar, Rohan Vijay; Samadzadeh, Kiana Michelle

    2012-01-01

    Abstract. Predicting the response of individual patients to cytotoxic chemotherapy drugs is critical for developing individualized therapies. With this motivation, an optical molecular imaging approach was developed to detect cisplatin induced changes in the uptake and intracellular retention of choline. Intracellular uptake of choline was characterized using a click chemistry reaction between propargyl choline and Alexa-488 azide. Cisplatin induced changes in the uptake of propargyl choline in cells and tumor spheroids were compared with similar measurements using a fluorescent analogue of deoxyglucose and conventional cell viability assays. Uptake and intracellular retention of propargyl choline decreased with an increase in concentration of cisplatin. Intracellular uptake of propargyl choline was significantly reduced within 3 h of incubation with a sub-lethal dose of cisplatin. Results demonstrate that the imaging approach based on propargyl choline was more sensitive in detecting the early response of cancer cells to cisplatin as compared to the imaging based on fluorescent analogue of deoxyglucose and cell viability assays. Imaging measurements in tumor spheroids show a significant decrease in the uptake of propargyl choline following treatment with cisplatin. Overall, the results demonstrate a novel optical molecular imaging approach for rapid measurement of the response of individual cancer cells to cisplatin treatment. PMID:23224005

  9. A Structural and Molecular Approach for the Study Biomarkers

    NASA Technical Reports Server (NTRS)

    Thomas-Keprta, Kathie; Vali, Hojatollah; Sears, S. Kelly; Roh, Yul

    2001-01-01

    Investigation of the nucleation and growth of crystals in both abiotic and biotic systems is critical to seemingly diverse disciplines of geology, biology, environmental science, and astrobiology. While there are abundant studies devoted to the determination of the structure and composition of inorganic crystals, as well as to the development of thermodynamic and kinetic models, it is only recently that research efforts have been directed towards understanding mineralization in biological systems (i.e., biomineralization). Biomineralization refers to the processes by which living organisms form inorganic solids. Studies of the processes of biomineralization under low temperature aqueous conditions have focused primarily on magnetite forming bacteria and shell forming marine organisms. Many of the biological building materials consist of inorganic minerals (calcium carbonate, calcium phosphate, silica or iron oxide) intricately combined with organic polymers (like proteins). More recently, efforts have been undertaken to explore the nature of biological activities in ancient rocks. In the absence of well-preserved microorganisms or genetic material required for the polmerase chain reaction (PCR) method in molecular phylogenetic studies, using biominerals as biomarkers offers an alternative approach for the recognition of biogenic activity in both terrestrial and extraterrestrial environments. The primary driving force in biomineralization is the interaction between organic and inorganic phases. Thus, the investigation of the ultrastructure and the nature of reactions at the molecular level occurring at the interface between inorganic and organic phases is essential to understanding the processes leading to the nucleation and growth of crystals. It is recognized that crystal surfaces can serve as the substrate for the organization of organic molecules that lead to the formation of polymers and other complex organic molecules, and in discussions of the origins of life

  10. A Structural and Molecular Approach for the Study Biomarkers

    NASA Technical Reports Server (NTRS)

    Thomas-Keprta, Kathie; Vali, Hojatollah; Sears, S. Kelly; Roh, Yul

    2001-01-01

    Investigation of the nucleation and growth of crystals in both abiotic and biotic systems is critical to seemingly diverse disciplines of geology, biology, environmental science, and astrobiology. While there are abundant studies devoted to the determination of the structure and composition of inorganic crystals, as well as to the development of thermodynamic and kinetic models, it is only recently that research efforts have been directed towards understanding mineralization in biological systems (i.e., biomineralization). Biomineralization refers to the processes by which living organisms form inorganic solids. Studies of the processes of biomineralization under low temperature aqueous conditions have focused primarily on magnetite forming bacteria and shell forming marine organisms. Many of the biological building materials consist of inorganic minerals (calcium carbonate, calcium phosphate, silica or iron oxide) intricately combined with organic polymers (like proteins). More recently, efforts have been undertaken to explore the nature of biological activities in ancient rocks. In the absence of well-preserved microorganisms or genetic material required for the polmerase chain reaction (PCR) method in molecular phylogenetic studies, using biominerals as biomarkers offers an alternative approach for the recognition of biogenic activity in both terrestrial and extraterrestrial environments. The primary driving force in biomineralization is the interaction between organic and inorganic phases. Thus, the investigation of the ultrastructure and the nature of reactions at the molecular level occurring at the interface between inorganic and organic phases is essential to understanding the processes leading to the nucleation and growth of crystals. It is recognized that crystal surfaces can serve as the substrate for the organization of organic molecules that lead to the formation of polymers and other complex organic molecules, and in discussions of the origins of life

  11. Molecular Paleoparasitological Hybridization Approach as Effective Tool for Diagnosing Human Intestinal Parasites from Scarce Archaeological Remains

    PubMed Central

    Jaeger, Lauren Hubert; Iñiguez, Alena Mayo

    2014-01-01

    Paleoparasitology is the science that uses parasitological techniques for diagnosing parasitic diseases in the past. Advances in molecular biology brought new insights into this field allowing the study of archaeological material. However, due to technical limitations a proper diagnosis and confirmation of the presence of parasites is not always possible, especially in scarce and degraded archaeological remains. In this study, we developed a Molecular Paleoparasitological Hybridization (MPH) approach using ancient DNA (aDNA) hybridization to confirm and complement paleoparasitological diagnosis. Eight molecular targets from four helminth parasites were included: Ascaris sp., Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis. The MPH analysis using 18th century human remains from Praça XV cemetery (CPXV), Rio de Janeiro, Brazil, revealed for the first time the presence E. vermicularis aDNA (50%) in archaeological sites of Brazil. Besides, the results confirmed T. trichiura and Ascaris sp. infections. The prevalence of infection by Ascaris sp. and E. vermicularis increased considerably when MPH was applied. However, a lower aDNA detection of T. trichiura (40%) was observed when compared to the diagnosis by paleoparasitological analysis (70%). Therefore, based on these data, we suggest a combination of Paleoparasitological and MPH approaches to verify the real panorama of intestinal parasite infection in human archeological samples. PMID:25162694

  12. 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…

  13. New Approaches to Molecular Imaging of Multiple Myeloma.

    PubMed

    Vij, Ravi; Fowler, Kathryn J; Shokeen, Monica

    2016-01-01

    Molecular imaging plays an important role in detection and staging of hematologic malignancies. Multiple myeloma (MM) is an age-related hematologic malignancy of clonal bone marrow plasma cells characterized by destructive bone lesions and is fatal in most patients. Traditional skeletal survey and bone scans have sensitivity limitations for osteolytic lesions manifested in MM. Progressive biomedical imaging technologies such as low-dose CT, molecularly targeted PET, MRI, and the functional-anatomic hybrid versions (PET/CT and PET/MRI) provide incremental advancements in imaging MM. Imaging with PET and MRI using molecularly targeted probes is a promising precision medicine platform that might successfully address the clinical ambiguities of myeloma spectrum diseases. The intent of this focus article is to provide a concise review of the present status and promising developments on the horizon, such as the new molecular imaging biomarkers under investigation that can either complement or potentially supersede existing standards. PMID:26541780

  14. Network-Based Models in Molecular Biology

    NASA Astrophysics Data System (ADS)

    Beyer, Andreas

    Biological systems are characterized by a large number of diverse interactions. Interaction maps have been used to abstract those interactions at all biological scales ranging from food webs at the ecosystem level down to protein interaction networks at the molecular scale.

  15. 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

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

    PubMed

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

    2012-11-21

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

  17. 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.

  18. An improved approach for predicting drug-target interaction: proteochemometrics to molecular docking.

    PubMed

    Shaikh, Naeem; Sharma, Mahesh; Garg, Prabha

    2016-02-23

    Proteochemometric (PCM) methods, which use descriptors of both the interacting species, i.e. drug and the target, are being successfully employed for the prediction of drug-target interactions (DTI). However, unavailability of non-interacting dataset and determining the applicability domain (AD) of model are a main concern in PCM modeling. In the present study, traditional PCM modeling was improved by devising novel methodologies for reliable negative dataset generation and fingerprint based AD analysis. In addition, various types of descriptors and classifiers were evaluated for their performance. The Random Forest and Support Vector Machine models outperformed the other classifiers (accuracies >98% and >89% for 10-fold cross validation and external validation, respectively). The type of protein descriptors had negligible effect on the developed models, encouraging the use of sequence-based descriptors over the structure-based descriptors. To establish the practical utility of built models, targets were predicted for approved anticancer drugs of natural origin. The molecular recognition interactions between the predicted drug-target pair were quantified with the help of a reverse molecular docking approach. The majority of predicted targets are known for anticancer therapy. These results thus correlate well with anticancer potential of the selected drugs. Interestingly, out of all predicted DTIs, thirty were found to be reported in the ChEMBL database, further validating the adopted methodology. The outcome of this study suggests that the proposed approach, involving use of the improved PCM methodology and molecular docking, can be successfully employed to elucidate the intricate mode of action for drug molecules as well as repositioning them for new therapeutic applications. PMID:26822863

  19. Molecular biology of the skin introduction: approaches and principles.

    PubMed

    Slater, C; Goldsmith, L A

    1993-09-01

    This issue of Seminars in Dermatology describes our current understanding of the molecular nature of skin diseases. Some would say it is hubris to even contemplate this charge considering the rapid progress in molecular genetics. We implore the gods protecting the nucleotides to look kindly on our efforts. This introductory article discussed some general methodological considerations and techniques and provides a glossary of common terms used in molecular biology, useful for understanding this issue of Seminars in Dermatology. This article is aimed at neophytes to enhance their ability to enter the magical realm of the gene. The articles in this issue describe diseases with a defined defect at the DNA level or diseases in which there is a rapid closing in on the basic defect. PMID:8217556

  20. Cellular and Molecular Biological Approaches to Interpreting Ancient Biomarkers

    NASA Astrophysics Data System (ADS)

    Newman, Dianne K.; Neubauer, Cajetan; Ricci, Jessica N.; Wu, Chia-Hung; Pearson, Ann

    2016-06-01

    Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of this progress. By way of example, we review how attempts to understand the biological function of 2-methylhopanoids in modern bacteria have changed our interpretation of what their molecular fossils tell us about the early history of life. They were once thought to be biomarkers of cyanobacteria and hence the evolution of oxygenic photosynthesis, but we now believe that 2-methylhopanoid biosynthetic capacity originated in the Alphaproteobacteria, that 2-methylhopanoids are regulated in response to stress, and that hopanoid 2-methylation enhances membrane rigidity. We present a new interpretation of 2-methylhopanes that bridges the gap between studies of the functions of 2-methylhopanoids and their patterns of occurrence in the rock record.

  1. A deoxyribozyme-based molecular automaton.

    PubMed

    Stojanovic, Milan N; Stefanovic, Darko

    2003-09-01

    We describe a molecular automaton, called MAYA, which encodes a version of the game of tic-tac-toe and interactively competes against a human opponent. The automaton is a Boolean network of deoxyribozymes that incorporates 23 molecular-scale logic gates and one constitutively active deoxyribozyme arrayed in nine wells (3x3) corresponding to the game board. To make a move, MAYA carries out an analysis of the input oligonucleotide keyed to a particular move by the human opponent and indicates a move by fluorescence signaling in a response well. The cycle of human player input and automaton response continues until there is a draw or a victory for the automaton. The automaton cannot be defeated because it implements a perfect strategy. PMID:12923549

  2. A quasi-classical mapping approach to vibrationally coupled electron transport in molecular junctions

    SciTech Connect

    Li, Bin; Miller, William H.; Wilner, Eli Y.; Thoss, Michael

    2014-03-14

    We develop a classical mapping approach suitable to describe vibrationally coupled charge transport in molecular junctions based on the Cartesian mapping for many-electron systems [B. Li and W. H. Miller, J. Chem. Phys. 137, 154107 (2012)]. To properly describe vibrational quantum effects in the transport characteristics, we introduce a simple transformation rewriting the Hamiltonian in terms of occupation numbers and use a binning function to facilitate quantization. The approach provides accurate results for the nonequilibrium Holstein model for a range of bias voltages, vibrational frequencies, and temperatures. It also captures the hallmarks of vibrational quantum effects apparent in step-like structure in the current-voltage characteristics at low temperatures as well as the phenomenon of Franck-Condon blockade.

  3. 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.

  4. Determinants of molecular reactivity as criteria for predicting toxicity: problems and approaches.

    PubMed Central

    Weinstein, H; Rabinowitz, J; Liebman, M N; Osman, R

    1985-01-01

    We discuss the physicochemical basis for mechanisms of action of toxic chemicals and theoretical methods that can be used to understand the relation to the structure of these chemicals. Molecular properties that determine the chemical reactivity of the compounds are proposed as parameters in the analysis of such structure-activity relationships and as criteria for predicting potential toxicity. The theoretical approaches include quantitative methods for structural superposition of molecules and for superposition of their reactivity characteristics. Applications to polychlorinated hydrocarbons are used to illustrate both rigid superposition methods, and methods that take advantage of structural flexibility. These approaches and their results are discussed and compared with methods that afford quantitative structural comparisons without direct superposition, with special emphasis on the need for efficient automated methods suitable for rapid scans of large structural data bases. Quantum mechanical methods for the calculation of molecular properties that can serve as reactivity criteria are presented and illustrated. Special attention is given to the electrostatic properties of the molecules such as the molecular electrostatic potential, the electric fields, and the polarizability terms calculated from perturbation expansions. The practical considerations related to the rapid calculation of these properties on relevant molecular surfaces (e.g., solvent- or reagent-accessible surfaces) are discussed and exemplified, stressing the special problems posed by the structural variety of toxic substances and the paucity of information on their mechanisms of action. The discussion leads to a rationale for the use of the combination of theoretical methods to reveal discriminant criteria for toxicity and to analyze the initial steps in the metabolic processes that could yield toxic products. PMID:3905371

  5. A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases

    PubMed Central

    Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A.

    2015-01-01

    Background: A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. Objectives: We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. Methods: For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Conclusions: Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Citation: Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that

  6. Coal-based carbons with molecular sieve properties

    SciTech Connect

    El-Wakil, A.M.; Youssef, A.M.; Tollan, K.A. )

    1991-01-01

    Carbon molecular sieves are used extensively in gas chromatography for the separation of permanent gases and light hydrocarbons. Carbon molecular sieves also find commercial application for the manufacture of pure hydrogen from hydrogen-rich gases such as coke-oven gas, and for the separation of air by the pressure-swing adsorption technique. The objective of this investigation was to prepare carbons from Maghara coal, recently available on the commercial market. Coal-based carbons, if they possess molecular sieve properties, are superior to molecular sieve carbons from agricultural by-products because they have more satisfactory mechanical properties.

  7. Proteogenomic Approaches for the Molecular Characterization of Natural Microbial Communities

    SciTech Connect

    Banfield, Jillian F.; Verberkmoes, Nathan C; Hettich, Robert {Bob} L; Thelen, Michael P.

    2005-01-01

    At the present time we know little about how microbial communities function in their natural habitats. For example, how do microorganisms interact with each other and their physical and chemical surroundings and respond to environmental perturbations? We might begin to answer these questions if we could monitor the ways in which metabolic roles are partitioned amongst members as microbial communities assemble, determine how resources such as carbon, nitrogen, and energy are allocated into metabolic pathways, and understand the mechanisms by which organisms and communities respond to changes in their surroundings. Because many organisms cannot be cultivated, and given that the metabolisms of those growing in monoculture are likely to differ from those of organisms growing as part of consortia, it is vital to develop methods to study microbial communities in situ. Chemoautotrophic biofilms growing in mine tunnels hundreds of meters underground drive pyrite (FeS2) dissolution and acid and metal release, creating habitats that select for a small number of organism types. The geochemical and microbial simplicity of these systems, the significant biomass, and clearly defined biological-inorganic feedbacks make these ecosystem microcosms ideal for development of methods for the study of uncultivated microbial consortia. Our approach begins with the acquisition of genomic data from biofilms that are sampled over time and in different growth conditions. We have demonstrated that it is possible to assemble shotgun sequence data to reveal the gene complement of the dominant community members and to use these data to confidently identify a significant fraction of proteins from the dominant organisms by mass spectrometry (MS)-based proteomics. However, there are technical obstacles currently restricting this type of "proteogenomic" analysis. Composite genomic sequences assembled from environmental data from natural microbial communities do not capture the full range of genetic

  8. Proteogenomic approaches for the molecular characterization of natural microbial communities.

    PubMed

    Banfield, Jillian F; Verberkmoes, Nathan C; Hettich, Robert L; Thelen, Michael P

    2005-01-01

    At the present time we know little about how microbial communities function in their natural habitats. For example, how do microorganisms interact with each other and their physical and chemical surroundings and respond to environmental perturbations? We might begin to answer these questions if we could monitor the ways in which metabolic roles are partitioned amongst members as microbial communities assemble, determine how resources such as carbon, nitrogen, and energy are allocated into metabolic pathways, and understand the mechanisms by which organisms and communities respond to changes in their surroundings. Because many organisms cannot be cultivated, and given that the metabolisms of those growing in monoculture are likely to differ from those of organisms growing as part of consortia, it is vital to develop methods to study microbial communities in situ. Chemoautotrophic biofilms growing in mine tunnels hundreds of meters underground drive pyrite (FeS(2)) dissolution and acid and metal release, creating habitats that select for a small number of organism types. The geochemical and microbial simplicity of these systems, the significant biomass, and clearly defined biological-inorganic feedbacks make these ecosystem microcosms ideal for development of methods for the study of uncultivated microbial consortia. Our approach begins with the acquisition of genomic data from biofilms that are sampled over time and in different growth conditions. We have demonstrated that it is possible to assemble shotgun sequence data to reveal the gene complement of the dominant community members and to use these data to confidently identify a significant fraction of proteins from the dominant organisms by mass spectrometry (MS)-based proteomics. However, there are technical obstacles currently restricting this type of "proteogenomic" analysis. Composite genomic sequences assembled from environmental data from natural microbial communities do not capture the full range of

  9. Unraveling the molecular effects of mutation L270P on Wiskkot-Aldrich syndrome protein: insights from molecular dynamics approach.

    PubMed

    Palaniappan, Chandrasekaran; Rao, Sethumadhavan; Ramalingam, Rajasekaran

    2016-09-01

    Missense mutation L270P disrupts the auto-inhibited state of "Wiskkot-Aldrich syndrome protein" (WASP), thereby constitutively activating the mutant structure, a key event for pathogenesis of X-linked neutropenia (XLN). In this study, we comprehensively deciphered the molecular feature of activated mutant structure by all atom molecular dynamics (MD) approach. MD analysis revealed that mutant structure exposed a wide variation in the spatial environment of atoms, resulting in enhanced residue flexibility. The increased flexibility of residues favored to decrease the number of intra-molecular hydrogen bonding interactions in mutant structure. The reduction of hydrogen bonds in the mutant structure resulted to disrupt the local folding of secondary structural elements that eventually affect the proper folding of mutants. The unfolded state of mutant structure established more number of inter-molecular hydrogen bonding interaction at interface level due to the conformational variability, thus mediated high binding affinity with its interacting partner, Cdc42. PMID:26457828

  10. A subgrid based approach for morphodynamic modelling

    NASA Astrophysics Data System (ADS)

    Volp, N. D.; van Prooijen, B. C.; Pietrzak, J. D.; Stelling, G. S.

    2016-07-01

    To improve the accuracy and the efficiency of morphodynamic simulations, we present a subgrid based approach for a morphodynamic model. This approach is well suited for areas characterized by sub-critical flow, like in estuaries, coastal areas and in low land rivers. This new method uses a different grid resolution to compute the hydrodynamics and the morphodynamics. The hydrodynamic computations are carried out with a subgrid based, two-dimensional, depth-averaged model. This model uses a coarse computational grid in combination with a subgrid. The subgrid contains high resolution bathymetry and roughness information to compute volumes, friction and advection. The morphodynamic computations are carried out entirely on a high resolution grid, the bed grid. It is key to find a link between the information defined on the different grids in order to guaranty the feedback between the hydrodynamics and the morphodynamics. This link is made by using a new physics-based interpolation method. The method interpolates water levels and velocities from the coarse grid to the high resolution bed grid. The morphodynamic solution improves significantly when using the subgrid based method compared to a full coarse grid approach. The Exner equation is discretised with an upwind method based on the direction of the bed celerity. This ensures a stable solution for the Exner equation. By means of three examples, it is shown that the subgrid based approach offers a significant improvement at a minimal computational cost.

  11. Engineering nanomaterials with a combined electrochemical and molecular biomimetic approach

    NASA Astrophysics Data System (ADS)

    Dai, Haixia

    Biocomposite materials, such as bones, teeth, and shells, are created using mild aqueous solution-based processes near room temperature. Proteins add flexibility to these processes by facilitating the nucleation, growth, and ordering of specific inorganic materials into hierarchical structures. We aim to develop a biomimetic strategy for engineering technologically relevant inorganic materials with controlled compositions and structures, as Nature does, using proteins to orchestrate material formation and assembly. This approach involves three basic steps: (i) preparation of inorganic substrates compatible with combinatorial polypeptide screening; (ii) identification of inorganic-binding polypeptides and their engineering into inorganic-binding proteins; and (iii) protein-mediated inorganic nucleation and organization. Cuprous oxide (Cu2O), a p-type semiconductor, has been used to demonstrate all three steps. Zinc oxide (ZnO), an n-type semiconductor, has been used to show the generality of selected steps. Step (i), preparation of high quality inorganic substrates to select inorganic-binding polypeptides, was accomplished using electrochemical microfabrication to grow and pattern Cu2O and ZnO. Raman spectroscopy and x-ray photoelectron spectroscopy were used to verify phase purity and compositional stability of these surfaces during polypeptide screening. Step (ii), accomplished in collaboration with personnel in Prof Baneyx' lab at the University of Washington, involved incubating the inorganic substrates with the FliTrx(TM) random peptide library to identify cysteine-constrained dodecapeptides that bind the targeted inorganic. Insertion of a Cu2O-binding dodecapeptide into the DNA-binding protein TraI endowed the engineered TraI with strong affinity for Cu2O (Kd ≈ 10 -8 M). Finally, step (iii) involved nonequilibrium synthesis and organization of Cu2O nanoparticles, taking advantage of the inorganic and DNA recognition properties of the engineered TraI. The

  12. Molecular bases of plant resistance to arthropods.

    PubMed

    Smith, C Michael; Clement, Stephen L

    2012-01-01

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

  13. 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.

  14. An Electronic Structure Approach to Charge Transfer and Transport in Molecular Building Blocks for Organic Optoelectronics

    NASA Astrophysics Data System (ADS)

    Hendrickson, Heidi Phillips

    technological design and development. Time dependent perturbation theory, employed by non-equilibrium Green's function formalism, is utilized to study the effect of quantum coherences on electron transport and the effect of symmetry breaking on the electronic spectra of model molecular junctions. The fourth part of this thesis presents the design of a physical chemistry course based on a pedagogical approach called Writing-to-Teach. The nature of inaccuracies expressed in student-generated explanations of quantum chemistry topics, and the ability of a peer review process to engage these inaccuracies, is explored within this context.

  15. Computing the blood brain barrier (BBB) diffusion coefficient: A molecular dynamics approach

    NASA Astrophysics Data System (ADS)

    Shamloo, Amir; Pedram, Maysam Z.; Heidari, Hossein; Alasty, Aria

    2016-07-01

    Various physical and biological aspects of the Blood Brain Barrier (BBB) structure still remain unfolded. Therefore, among the several mechanisms of drug delivery, only a few have succeeded in breaching this barrier, one of which is the use of Magnetic Nanoparticles (MNPs). However, a quantitative characterization of the BBB permeability is desirable to find an optimal magnetic force-field. In the present study, a molecular model of the BBB is introduced that precisely represents the interactions between MNPs and the membranes of Endothelial Cells (ECs) that form the BBB. Steered Molecular Dynamics (SMD) simulations of the BBB crossing phenomenon have been carried out. Mathematical modeling of the BBB as an input-output system has been considered from a system dynamics modeling viewpoint, enabling us to analyze the BBB behavior based on a robust model. From this model, the force profile required to overcome the barrier has been extracted for a single NP from the SMD simulations at a range of velocities. Using this data a transfer function model has been obtained and the diffusion coefficient is evaluated. This study is a novel approach to bridge the gap between nanoscale models and microscale models of the BBB. The characteristic diffusion coefficient has the nano-scale molecular effects inherent, furthermore reducing the computational costs of a nano-scale simulation model and enabling much more complex studies to be conducted.

  16. Approaches to isolation and molecular characterization of disseminated tumor cells

    PubMed Central

    Magbanua, Mark Jesus M.; Das, Rishi; Polavarapu, Prithi; Park, John W.

    2015-01-01

    Micrometastatic cells in the bone marrow, now usually referred to as “disseminated tumor cells (DTCs)”, can be detected in early stage cancer patients. It has been hypothesized that DTCs represent key intermediates in the metastatic process as possible precursors of bone and visceral metastases, and are indicators of metastatic potential. Indeed, multiple clinical studies have unequivocally demonstrated the prognostic value of these cells in breast and other cancers, as DTCs have been associated with adverse outcomes, including inferior overall and disease-free survival. Despite this established clinical significance, the molecular nature of DTCs remains elusive. The complexity of the bone marrow poses a unique challenge in the isolation and direct characterization of these rare cells. However, recent advances in rare-cell technology along with technical improvements in analyzing limited cell inputs have enabled the molecular profiling of DTCs. In this review, we discuss research featuring the isolation and genomic analysis of DTCs. Emerging work on the molecular characterization of DTCs is now providing new insights into the biology of these cells. PMID:26378808

  17. Description of ionization in the molecular approach to atomic collisions

    SciTech Connect

    Harel, C.; Jouin, H.; Pons, B.; Errea, L.F.; Mendez, L.; Riera, A.

    1997-01-01

    Molecular treatments of atomic collisions have traditionally been restricted to low nuclear velocities because of their failure to reproduce the fall of the capture cross sections at higher velocities. The limitation has recently been seen to be due to their description of ionizing processes. This feature is shown here to be a general one for multicharged ion-atom collisions. Its origin and characteristics are described and illustrated for the prototypical Li{sup 3+}+H(1s) reaction. Ionization appears as a result of the inertia of the electron cloud to adiabatically follow the nuclear motion. This gives rise to nonadiabatic transitions, which represent an ionizing flux whenever the nuclear velocity is high enough that the energy of the traveling molecular orbitals involved is positive in both moving atomic reference frames. Two strongly connected mechanisms appear, corresponding to the relative translational and rotational nuclear motions. Because of the finiteness of the basis, these mechanisms terminate with unphysical trapping effects. While interesting {ital per se}, knowledge of these features is also useful with respect to improving molecular treatments of atomic collisions with the addition of pseudostates. {copyright} {ital 1996} {ital The American Physical Society}

  18. Ridge-based bias potentials to accelerate molecular dynamics.

    PubMed

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

    2015-12-28

    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. PMID:26723648

  19. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thalian. Final report

    SciTech Connect

    Gibson, S. I.

    2000-06-01

    This is a final report describing the results of the research funded by the DOE Energy Biosciences Program grant entitled ''A Molecular-Genetic Approach to Studying Source-Sink Interactions in Arabidiopsis thaliana''.

  20. A Known-to-Unknown Approach To Teach about Empirical and Molecular Formulas.

    ERIC Educational Resources Information Center

    Thamburaj, P. K.

    2001-01-01

    Points out student struggles with the determination of empirical and molecular formulas and introduces a teaching approach to increase student understanding. Uses scenarios to present the experimental data before presenting the problem. (YDS)

  1. Ab initio quantum mechanical/molecular mechanical simulation of electron transfer process: Fractional electron approach

    NASA Astrophysics Data System (ADS)

    Zeng, Xiancheng; Hu, Hao; Hu, Xiangqian; Cohen, Aron J.; Yang, Weitao

    2008-03-01

    Electron transfer (ET) reactions are one of the most important processes in chemistry and biology. Because of the quantum nature of the processes and the complicated roles of the solvent, theoretical study of ET processes is challenging. To simulate ET processes at the electronic level, we have developed an efficient density functional theory (DFT) quantum mechanical (QM)/molecular mechanical (MM) approach that uses the fractional number of electrons as the order parameter to calculate the redox free energy of ET reactions in solution. We applied this method to study the ET reactions of the aqueous metal complexes Fe(H2O)62+/3+ and Ru(H2O)62+/3+. The calculated oxidation potentials, 5.82 eV for Fe(II/III) and 5.14 eV for Ru(II/III), agree well with the experimental data, 5.50 and 4.96 eV, for iron and ruthenium, respectively. Furthermore, we have constructed the diabatic free energy surfaces from histogram analysis based on the molecular dynamics trajectories. The resulting reorganization energy and the diabatic activation energy also show good agreement with experimental data. Our calculations show that using the fractional number of electrons (FNE) as the order parameter in the thermodynamic integration process leads to efficient sampling and validate the ab initio QM/MM approach in the calculation of redox free energies.

  2. Integrating molecular and morphological approaches for characterizing parasite cryptic species: implications for parasitology.

    PubMed

    Nadler, Steven A; DE León, Gerardo Pérez-Ponce

    2011-11-01

    Herein we review theoretical and methodological considerations important for finding and delimiting cryptic species of parasites (species that are difficult to recognize using traditional systematic methods). Applications of molecular data in empirical investigations of cryptic species are discussed from an historical perspective, and we evaluate advantages and disadvantages of approaches that have been used to date. Developments concerning the theory and practice of species delimitation are emphasized because theory is critical to interpretation of data. The advantages and disadvantages of different molecular methodologies, including the number and kind of loci, are discussed relative to tree-based approaches for detecting and delimiting cryptic species. We conclude by discussing some implications that cryptic species have for research programmes in parasitology, emphasizing that careful attention to the theory and operational practices involved in finding, delimiting, and describing new species (including cryptic species) is essential, not only for fully characterizing parasite biodiversity and broader aspects of comparative biology such as systematics, evolution, ecology and biogeography, but to applied research efforts that strive to improve development and understanding of epidemiology, diagnostics, control and potential eradication of parasitic diseases. PMID:21281559

  3. Inquiry-Based Learning of Molecular Phylogenetics

    ERIC Educational Resources Information Center

    Campo, Daniel; Garcia-Vazquez, Eva

    2008-01-01

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

  4. Slow approach to steady motion of a concave body in a free-molecular gas.

    PubMed

    Tsuji, Tetsuro; Arai, Junichi; Kawano, Satoyuki

    2015-07-01

    A body in a free-molecular gas accelerated by a constant external force is considered on the basis of kinetic theory. The body is an infinitely long rectangular hollow column with one face removed, and thus it has a squarish U-shaped cross section. The concave part of the body points toward the direction of motion, and thus the gas molecules may be trapped in the concavity. Gas molecules undergo diffuse reflection on a base part, whereas specular reflection on two lateral parts. It is numerically shown that the velocity of the body approaches a terminal velocity, for which a drag force exerted by the gas counterbalances the external force, in such a way that their difference decreases in proportion to the inverse square of time for a large time. This rate of approach is slower than the known rate proportional to the inverse cube of time in the case of a body without concavity [Aoki et al., Phys. Rev. E 80, 016309 (2009)]. Based on the detailed investigation on the velocity distribution function of gas molecules impinging on the body, it is clarified that the concavity prevents some molecules from escaping to infinity. This trapping enhances the effect of recollision between the body and the gas molecules, which is the cause of the inverse power laws, and thus leads to the slower approach. PMID:26274147

  5. Slow approach to steady motion of a concave body in a free-molecular gas

    NASA Astrophysics Data System (ADS)

    Tsuji, Tetsuro; Arai, Junichi; Kawano, Satoyuki

    2015-07-01

    A body in a free-molecular gas accelerated by a constant external force is considered on the basis of kinetic theory. The body is an infinitely long rectangular hollow column with one face removed, and thus it has a squarish U -shaped cross section. The concave part of the body points toward the direction of motion, and thus the gas molecules may be trapped in the concavity. Gas molecules undergo diffuse reflection on a base part, whereas specular reflection on two lateral parts. It is numerically shown that the velocity of the body approaches a terminal velocity, for which a drag force exerted by the gas counterbalances the external force, in such a way that their difference decreases in proportion to the inverse square of time for a large time. This rate of approach is slower than the known rate proportional to the inverse cube of time in the case of a body without concavity [Aoki et al., Phys. Rev. E 80, 016309 (2009), 10.1103/PhysRevE.80.016309]. Based on the detailed investigation on the velocity distribution function of gas molecules impinging on the body, it is clarified that the concavity prevents some molecules from escaping to infinity. This trapping enhances the effect of recollision between the body and the gas molecules, which is the cause of the inverse power laws, and thus leads to the slower approach.

  6. Concise NMR approach for molecular dynamics characterizations in organic solids.

    PubMed

    Aliev, Abil E; Courtier-Murias, Denis

    2013-08-22

    Molecular dynamics characterisations in solids can be carried out selectively using dipolar-dephasing experiments. Here we show that the introduction of a sum of Lorentzian and Gaussian functions greatly improve fittings of the "intensity versus time" data for protonated carbons in dipolar-dephasing experiments. The Lorentzian term accounts for remote intra- and intermolecular (1)H-(13)C dipole-dipole interactions, which vary from one molecule to another or for different carbons within the same molecule. Thus, by separating contributions from weak remote interactions, more accurate Gaussian decay constants, T(dd), can be extracted for directly bonded (1)H-(13)C dipole-dipole interactions. Reorientations of the (1)H-(13)C bonds lead to the increase of T(dd), and by measuring dipolar-dephasing constants, insight can be gained into dynamics in solids. We have demonstrated advantages of the method using comparative dynamics studies in the α and γ polymorphs of glycine, cyclic amino acids L-proline, DL-proline and trans-4-hydroxy-L-proline, the Ala residue in different dipeptides, as well as adamantane and hexamethylenetetramine. It was possible to distinguish subtle differences in dynamics of different carbon sites within a molecule in polymorphs and in L- and DL-forms. The presence of overall molecular motions is shown to lead to particularly large differences in dipolar-dephasing experiments. The differences in dynamics can be attributed to differences in noncovalent interactions. In the case of hexamethylenetetramine, for example, the presence of C-H···N interactions leads to nearly rigid molecules. Overall, the method allows one to gain insight into the role of noncovalent interactions in solids and their influence on the molecular dynamics. PMID:23879450

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

    PubMed

    Ji, S

    1999-10-01

    The pioneering work of Adleman (1994) demonstrated that DNA molecules in test tubes can be manipulated to perform a certain type of mathematical computation. This has stimulated a theoretical interest in the possibility of constructing DNA-based molecular computers. To gauge the practicality of realizing such microscopic computers, it was thought necessary to learn as much as possible from the biology of the living cell--presently the only known DNA-based molecular computer in existence. Here the recently developed theoretical model of the living cell (the Bhopalator) and its associated theories (e.g. cell language), principles, laws and concepts (e.g. conformons, IDS's) are briefly reviewed and summarized in the form of a set of five laws of 'molecular semiotics' (synonyms include 'microsemiotics', 'cellular semiotics', or 'cytosemiotics') the study of signs mediating measurement, computation, and communication on the cellular and molecular levels. Hopefully, these laws will find practical applications in designing DNA-based computing systems. PMID:10636037

  8. Physics-based approach to haptic display

    NASA Technical Reports Server (NTRS)

    Brown, J. Michael; Colgate, J. Edward

    1994-01-01

    This paper addresses the implementation of complex multiple degree of freedom virtual environments for haptic display. We suggest that a physics based approach to rigid body simulation is appropriate for hand tool simulation, but that currently available simulation techniques are not sufficient to guarantee successful implementation. We discuss the desirable features of a virtual environment simulation, specifically highlighting the importance of stability guarantees.

  9. Molecular approaches to human polygenic disease - Symposium 130

    SciTech Connect

    Not Available

    1987-01-01

    This volume deals with the application of recombinant DNA techniques to the identification of diseases that have more than one inherited component. Focus is on the polygenic factors responsible for coronary atherosclerosis. Several other disorders having a polygenic orgin are also discussed, including hypertension, diabetes mellitus, psychiatric diseases, and autoimmune (HLA-related) disorders. Problems raised by the study of different families or different populations are covered, as well as the possibility of applying molecular techniques to disease prevention-for example, through gene therapy. Also explored are some of the ethical issues that relate to human gene mapping.

  10. A complex systems approach to computational molecular biology

    SciTech Connect

    Lapedes, A. |

    1993-09-01

    We report on the containing research program at Santa Fe Institute that applies complex systems methodology to computational molecular biology. Two aspects are stressed here are the use of co-evolving adaptive neutral networks for determining predictable protein structure classifications, and the use of information theory to elucidate protein structure and function. A ``snapshot`` of the current state of research in these two topics is presented, representing the present state of two major research thrusts in the program of Genetic Data and Sequence Analysis at the Santa Fe Institute.

  11. Dynamic molecules: molecular dynamics for everyone. An internet-based access to molecular dynamic simulations: basic concepts.

    PubMed

    Frank, Martin; Gutbrod, Peter; Hassayoun, Chokri; von Der Lieth, Claus-W

    2003-10-01

    Molecular dynamics is a rapidly developing field of science and has become an established tool for studying the dynamic behavior of biomolecules. Although several high quality programs for performing molecular dynamic simulations are freely available, only well-trained scientists are currently able to make use of the broad scientific potential that molecular dynamic simulations offer to gain insight into structural questions at an atomic level. The "Dynamic Molecules" approach is the first internet portal that provides an interactive access to set up, perform and analyze molecular dynamic simulations. It is completely based on standard web technologies and uses only publicly available software. The aim is to open molecular dynamics techniques to a broader range of users including undergraduate students, teachers and scientists outside the bioinformatics field. The time-limiting factors are the availability of free capacity on the computing server to run the simulations and the time required to transport the history file through the internet for the animation mode. The interactive access mode of the portal is acceptable for animations of molecules having up to about 500 atoms. PMID:12908101

  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. PMID:27372059

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

    PubMed Central

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

    2013-01-01

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

  14. 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)

  15. A molecular approach to comparative phylogeography of extant Malagasy lemurs

    PubMed Central

    Pastorini, Jennifer; Thalmann, Urs; Martin, Robert D.

    2003-01-01

    The lemurs of Madagascar provide an excellent model for exploring evolutionary diversification. This study investigates genetic divergence among most extant lemur taxa in relation to potential geographical boundaries to gene flow. For this purpose, ≈2,400 bp of mitochondrial DNA (part of the COIII gene; ND3, ND4L, and ND4 genes; and five tRNAs) were sequenced in a total of 131 lemurs from 5 families, 12 genera, 25 species, and 18 subspecies to reconstruct phylogenetic relationships among them. The comprehensive range of taxa makes this a particularly suitable molecular data set to examine lemur evolution. Those data clearly reveal that the Betsiboka River acts as an isolating barrier between populations of lemurs in north-western Madagascar. The Tsiribihina River similarly serves as a barrier to gene flow between northern and southern populations of lemurs in central western Madagascar, whereas the Mahavavy River does not seem to lead to genetic isolation of lemur populations. Several discrepancies among molecular data, current taxonomy, and geographic distribution along the western coast emerged. Examination of geographical distribution of the taxa concerned in comparison with distribution boundaries of other lemur taxa in that region yielded explanations for these inconsistencies. Eulemur fulvus and Eulemur mongoz are the only lemur taxa that also occur outside Madagascar, on the Comoro Islands. Genetic data show no significant differentiation between Malagasy and Comorian populations of these species, supporting the interpretation that both were introduced only recently to the Comoro Islands. PMID:12719521

  16. Molecular self-assembly approaches for supramolecular electronic and organic electronic devices

    NASA Astrophysics Data System (ADS)

    Yip, Hin-Lap

    Molecular self-assembly represents an efficient bottom-up strategy to generate structurally well-defined aggregates of semiconducting pi-conjugated materials. The capability of tuning the chemical structures, intermolecular interactions and nanostructures through molecular engineering and novel materials processing renders it possible to tailor a large number of unprecedented properties such as charge transport, energy transfer and light harvesting. This approach does not only benefit traditional electronic devices based on bulk materials, but also generate a new research area so called "supramolecular electronics" in which electronic devices are built up with individual supramolecular nanostructures with size in the sub-hundred nanometers range. My work combined molecular self-assembly together with several novel materials processing techniques to control the nucleation and growth of organic semiconducting nanostructures from different type of pi-conjugated materials. By tailoring the interactions between the molecules using hydrogen bonds and pi-pi stacking, semiconducting nanoplatelets and nanowires with tunable sizes can be fabricated in solution. These supramolecular nanostructures were further patterned and aligned on solid substrates through printing and chemical templating methods. The capability to control the different hierarchies of organization on surface provides an important platform to study their structural-induced electronic properties. In addition to using molecular self-assembly to create different organic nanostructures, functional self-assembled monolayer (SAM) formed by spontaneous chemisorption on surfaces was used to tune the interfacial property in organic solar cells. Devices showed dramatically improved performance when appropriate SAMs were applied to optimize the contact property for efficiency charge collection.

  17. Molecular Location Sensing Approach by Anisotropic Magnetism of an Endohedral Metallofullerene.

    PubMed

    Takano, Yuta; Tashita, Ryo; Suzuki, Mitsuaki; Nagase, Shigeru; Imahori, Hiroshi; Akasaka, Takeshi

    2016-06-29

    Location recognition at the molecular scale provides valuable information about the nature of functional molecular materials. This study presents a novel location sensing approach based on an endohedral metallofullerene, Ce@C82, using its anisotropic magnetic properties, which lead to temperature-dependent paramagnetic shifts in (1)H NMR spectra. Five site-isomers of Ce@C82CH2-3,5-C6H3Me2 were synthesized to demonstrate the spatial sensing ability of Ce@C82. Single-crystal structures, absorption spectra, and density functional theory calculations were used to select the plausible addition positions in the radical coupling reaction, which preferentially happens on the carbon atoms with high electron density of the singly occupied molecular orbital (SOMO) and positive charge. Temperature-dependent NMR measurements demonstrated unique paramagnetic shifts of the (1)H peaks, which were derived from the anisotropic magnetism of the f-electron in the Ce atom of the isomers. It was found that the magnetic anisotropy axes can be easily predicted by theoretical calculations using the Gaussian 09 package. Further analysis revealed that the temperature-dependent trend in the shifts is clearly predictable from the distance and relative position of the proton from the Ce atom. Hence, the Ce-encapsulated metallofullerene Ce@C82 can provide spatial location information about nearby atoms through the temperature-dependent paramagnetic shifts of its NMR signals. It can act as a molecular probe for location sensing by utilizing the anisotropic magnetism of the encapsulated Ce atom. The potentially low toxicity and stability of the endohedral fullerene would make Ce@C82 suitable for applications in biology and material science. PMID:27314267

  18. Optimal separable bases and molecular collisions

    SciTech Connect

    Poirier, L W

    1997-12-01

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

  19. Integrative systems medicine approaches to identify molecular targets in lymphoid malignancies.

    PubMed

    Frazzi, Raffaele; Auffray, Charles; Ferrari, Angela; Filippini, Perla; Rutella, Sergio; Cesario, Alfredo

    2016-01-01

    Although survival rates for lymphoproliferative disorders are steadily increasing both in the US and in Europe, there is need for optimizing front-line therapies and developing more effective salvage strategies. Recent advances in molecular genetics have highlighted the biological diversity of lymphoproliferative disorders. In particular, integrative approaches including whole genome sequencing, whole exome sequencing, and transcriptome or RNA sequencing have been instrumental to the identification of molecular targets for treatment. Herein, we will discuss how genomic, epigenomic and proteomic approaches in lymphoproliferative disorders have supported the discovery of molecular lesions and their therapeutic targeting in the clinic. PMID:27580852

  20. Advanced Approach of Multiagent Based Buoy Communication

    PubMed Central

    Gricius, Gediminas; Drungilas, Darius; Andziulis, Arunas; Dzemydiene, Dale; Voznak, Miroslav; Kurmis, Mindaugas; Jakovlev, Sergej

    2015-01-01

    Usually, a hydrometeorological information system is faced with great data flows, but the data levels are often excessive, depending on the observed region of the water. The paper presents advanced buoy communication technologies based on multiagent interaction and data exchange between several monitoring system nodes. The proposed management of buoy communication is based on a clustering algorithm, which enables the performance of the hydrometeorological information system to be enhanced. The experiment is based on the design and analysis of the inexpensive but reliable Baltic Sea autonomous monitoring network (buoys), which would be able to continuously monitor and collect temperature, waviness, and other required data. The proposed approach of multiagent based buoy communication enables all the data from the costal-based station to be monitored with limited transition speed by setting different tasks for the agent-based buoy system according to the clustering information. PMID:26345197

  1. Advanced Approach of Multiagent Based Buoy Communication.

    PubMed

    Gricius, Gediminas; Drungilas, Darius; Andziulis, Arunas; Dzemydiene, Dale; Voznak, Miroslav; Kurmis, Mindaugas; Jakovlev, Sergej

    2015-01-01

    Usually, a hydrometeorological information system is faced with great data flows, but the data levels are often excessive, depending on the observed region of the water. The paper presents advanced buoy communication technologies based on multiagent interaction and data exchange between several monitoring system nodes. The proposed management of buoy communication is based on a clustering algorithm, which enables the performance of the hydrometeorological information system to be enhanced. The experiment is based on the design and analysis of the inexpensive but reliable Baltic Sea autonomous monitoring network (buoys), which would be able to continuously monitor and collect temperature, waviness, and other required data. The proposed approach of multiagent based buoy communication enables all the data from the costal-based station to be monitored with limited transition speed by setting different tasks for the agent-based buoy system according to the clustering information. PMID:26345197

  2. An Integrated, Statistical Molecular Approach to the Physical Chemistry Curriculum

    ERIC Educational Resources Information Center

    Cartier, Stephen F.

    2009-01-01

    As an alternative to the "thermodynamics first" or "quantum first" approaches to the physical chemistry curriculum, the statistical definition of entropy and the Boltzmann distribution are introduced in the first days of the course and the entire two-semester curriculum is then developed from these concepts. Once the tools of statistical mechanics…

  3. Molecular Genetic Approaches to Human Diseases Involving Mental Retardation.

    ERIC Educational Resources Information Center

    Latt, Samuel A.; And Others

    1984-01-01

    Recombinant DNA techniques provide new approaches to the diagnosis and analysis of inherited human diseases associated with mental retardation, such as Lesch-Nyhan syndrome, phenylketonauria, the Fragile X syndrome, Down syndrome, and those associated with deletions or duplications of subchromosomal regions. (Author/CL)

  4. 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. PMID:23703909

  5. A semi-analytical approach to molecular dynamics

    NASA Astrophysics Data System (ADS)

    Michels, Dominik L.; Desbrun, Mathieu

    2015-12-01

    Despite numerous computational advances over the last few decades, molecular dynamics still favors explicit (and thus easily-parallelizable) time integrators for large scale numerical simulation. As a consequence, computational efficiency in solving its typically stiff oscillatory equations of motion is hampered by stringent stability requirements on the time step size. In this paper, we present a semi-analytical integration scheme that offers a total speedup of a factor 30 compared to the Verlet method on typical MD simulation by allowing over three orders of magnitude larger step sizes. By efficiently approximating the exact integration of the strong (harmonic) forces of covalent bonds through matrix functions, far improved stability with respect to time step size is achieved without sacrificing the explicit, symplectic, time-reversible, or fine-grained parallelizable nature of the integration scheme. We demonstrate the efficiency and scalability of our integrator on simulations ranging from DNA strand unbinding and protein folding to nanotube resonators.

  6. Molecular approaches for manipulating astrocytic signaling in vivo

    PubMed Central

    Xie, Alison X.; Petravicz, Jeremy; McCarthy, Ken D.

    2015-01-01

    Astrocytes are the predominant glial type in the central nervous system and play important roles in assisting neuronal function and network activity. Astrocytes exhibit complex signaling systems that are essential for their normal function and the homeostasis of the neural network. Altered signaling in astrocytes is closely associated with neurological and psychiatric diseases, suggesting tremendous therapeutic potential of these cells. To further understand astrocyte function in health and disease, it is important to study astrocytic signaling in vivo. In this review, we discuss molecular tools that enable the selective manipulation of astrocytic signaling, including the tools to selectively activate and inactivate astrocyte signaling in vivo. Lastly, we highlight a few tools in development that present strong potential for advancing our understanding of the role of astrocytes in physiology, behavior, and pathology. PMID:25941472

  7. Genetic variants in Alzheimer disease - molecular and brain network approaches.

    PubMed

    Gaiteri, Chris; Mostafavi, Sara; Honey, Christopher J; De Jager, Philip L; Bennett, David A

    2016-07-01

    Genetic studies in late-onset Alzheimer disease (LOAD) are aimed at identifying core disease mechanisms and providing potential biomarkers and drug candidates to improve clinical care of AD. However, owing to the complexity of LOAD, including pathological heterogeneity and disease polygenicity, extraction of actionable guidance from LOAD genetics has been challenging. Past attempts to summarize the effects of LOAD-associated genetic variants have used pathway analysis and collections of small-scale experiments to hypothesize functional convergence across several variants. In this Review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effects of LOAD-associated genetic variants. We then discuss emerging combinations of these omic data sets into multiscale models, which provide a more comprehensive representation of the effects of LOAD-associated genetic variants at multiple biophysical scales. Furthermore, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models. PMID:27282653

  8. A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water

    NASA Astrophysics Data System (ADS)

    Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul

    2016-03-01

    The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a "first-principles" DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand.

  9. A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water.

    PubMed

    Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul

    2016-03-21

    The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a "first-principles" DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand. PMID:27004884

  10. Condensed-to-atoms hardness kernel from the response of molecular fragment approach

    NASA Astrophysics Data System (ADS)

    Miranda-Quintana, Ramón Alain

    2016-08-01

    Condensed reactivity descriptors obtained from the response of molecular fragment (RMF) approach are analyzed within the variational formulation of conceptual density functional theory. It is shown that this approach can serve as the basis of a coherent formulation of the hardness kernel.

  11. A Coupled Meshless Technique/Molecular Dynamics Approach for Deformation Characterization of Mono-crystalline Metal

    SciTech Connect

    Gu, Y. T.; Yarlagadda, Prasad K. D. V.

    2010-05-21

    This paper presents a multiscale study using the coupled Meshless technique/Molecular Dynamics (M{sup 2}) for exploring the deformation mechanism of mono-crystalline metal (focus on copper) under uniaxial tension. In M{sup 2}, an advanced transition algorithm using transition particles is employed to ensure the compatibility of both displacements and their gradients, and an effective local quasi-continuum approach is also applied to obtain the equivalent continuum strain energy density based on the atomistic potentials and Cauchy-Born rule. The key parameters used in M{sup 2} are firstly investigated using a benchmark problem. Then, M{sup 2} is applied to the multiscale simulation for a mono-crystalline copper bar. It has found that the mono-crystalline copper has very good elongation property, and the ultimate strength and Young's modulus are much higher than those obtained in macro-scale.

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

    PubMed

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

    2012-03-01

    Supramolecular polymers, polymeric systems beyond the molecule, have attracted more and more attention from scientists due to their applications in various fields, including stimuli-responsive materials, healable materials, and drug delivery. Due to their good selectivity and convenient enviro-responsiveness, crown ether-based molecular recognition motifs have been actively employed to fabricate supramolecular polymers with interesting properties and novel applications in recent years. In this tutorial review, we classify supramolecular polymers based on their differences in topology and cover recent advances in the marriage between crown ether-based molecular recognition and polymer science. PMID:22012256

  13. Species and hybrid identification of sturgeon caviar: a new molecular approach to detect illegal trade.

    PubMed

    Boscari, E; Barmintseva, A; Pujolar, J M; Doukakis, P; Mugue, N; Congiu, L

    2014-05-01

    Overexploitation of wild populations due to the high economic value of caviar has driven sturgeons to near extinction. The high prices commanded by caviar on world markets have made it a magnet for illegal and fraudulent caviar trade, often involving low-value farmed caviar being sold as top-quality caviar. We present a new molecular approach for the identification of pure sturgeon species and hybrids that are among the most commercialized species in Europe and North America. Our test is based on the discovery of species-specific single nucleotide polymorphisms (SNPs) in the ribosomal protein S7, supplemented with the Vimentin gene and the mitochondrial D-loop. Test validations performed in 702 specimens of target and nontarget sturgeon species demonstrated a 100% identification success for Acipenser naccarii, A. fulvescens, A. stellatus, A. sinensis and A. transmontanus. In addition to species identification, our approach allows the identification of Bester and AL hybrids, two of the most economically important hybrids in the world, with 80% and 100% success, respectively. Moreover, the approach has the potential to identify many other existing sturgeon hybrids. The development of a standardized sturgeon identification tool will directly benefit trade law enforcement, providing the tools to monitor and regulate the legal trade of caviar and protect sturgeon stocks from illicit producers and traders, hence contributing to safeguarding this group of heavily threatened species. PMID:24219811

  14. A Statistical Approach for the Concurrent Coupling of Molecular Dynamics and Finite Element Methods

    NASA Technical Reports Server (NTRS)

    Saether, E.; Yamakov, V.; Glaessgen, E.

    2007-01-01

    Molecular dynamics (MD) methods are opening new opportunities for simulating the fundamental processes of material behavior at the atomistic level. However, increasing the size of the MD domain quickly presents intractable computational demands. A robust approach to surmount this computational limitation has been to unite continuum modeling procedures such as the finite element method (FEM) with MD analyses thereby reducing the region of atomic scale refinement. The challenging problem is to seamlessly connect the two inherently different simulation techniques at their interface. In the present work, a new approach to MD-FEM coupling is developed based on a restatement of the typical boundary value problem used to define a coupled domain. The method uses statistical averaging of the atomistic MD domain to provide displacement interface boundary conditions to the surrounding continuum FEM region, which, in return, generates interface reaction forces applied as piecewise constant traction boundary conditions to the MD domain. The two systems are computationally disconnected and communicate only through a continuous update of their boundary conditions. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM) as opposed to a direct coupling method where interface atoms and FEM nodes are individually related. The methodology is inherently applicable to three-dimensional domains, avoids discretization of the continuum model down to atomic scales, and permits arbitrary temperatures to be applied.

  15. MOLECULAR DIVERSITY OF DRINKING WATER MICROBIAL COMMUNITIES: A PHYLOGENETIC APPROACH

    EPA Science Inventory

    Culture-based methods are traditionally used to determine microbiological quality of drinking water even though these methods are highly selective and tend to underestimate the densities and diversity bacterial populations inhabiting distribution systems. In order to better under...

  16. Cleaning graphene: A first quantum/classical molecular dynamics approach

    NASA Astrophysics Data System (ADS)

    Delfour, L.; Davydova, A.; Despiau-Pujo, E.; Cunge, G.; Graves, D. B.; Magaud, L.

    2016-03-01

    Graphene outstanding properties created a huge interest in the condensed matter community and unprecedented fundings at the international scale in the hope of application developments. Recently, there have been several reports of incomplete removal of the polymer resists used to transfer as-grown graphene from one substrate to another, resulting in altered graphene transport properties. Finding a large-scale solution to clean graphene from adsorbed residues is highly desirable and one promising possibility would be to use hydrogen plasmas. In this spirit, we couple here quantum and classical molecular dynamics simulations to explore the kinetic energy ranges required by atomic hydrogen to selectively etch a simple residue—a CH3 group—without irreversibly damaging the graphene. For incident energies in the 2-15 eV range, the CH3 radical can be etched by forming a volatile CH4 compound which leaves the surface, either in the CH4 form or breaking into CH3 + H fragments, without further defect formation. At this energy, adsorption of H atoms on graphene is possible and further annealing will be required to recover pristine graphene.

  17. Trace element nutrition of infants--molecular approaches.

    PubMed

    Lönnerdal, Bo

    2005-01-01

    Newborn infants are exposed to widely varying intakes of trace elements, but little is known about their ability to homeostatically adjust to these intakes. Recent discoveries of several metal ion transporters in the small intestine are likely to enhance our understanding of molecular mechanisms regulating trace element absorption. Iron absorption is regulated by divalent metal ion transporter 1 (DMT1) and ferroportin 1 (FPN1). Studies on human infants have shown that young infants cannot regulate iron absorption, whereas older infants can. Our studies on infant rat pups show that there is no regulation of DMT1 and FPN1 at young age, but that this develops at older age. These findings may explain adverse effects of iron supplementation on growth in young human infants. Zinc absorption in the small intestine is regulated by the transporters ZnT1, ZnT2, ZnT4 and Zip-4 and zinc status affects the expression of these transporters in an attempt to achieve zinc homeostasis. Copper absorption is regulated by the transporters Ctrl, Atp7A and Atp7B, and exposure to copper at early age affects the expression and cellular localization of these proteins, affecting copper uptake and transport. To date, most studies on homeostatic regulation of trace mineral absorption have been done in cell systems and animal models; further studies on human infants are needed. The consequences of trace element interactions during infancy also need to be investigated in more detail. PMID:16240664

  18. Nuclear structure and reactions in the fermionic molecular dynamics approach

    NASA Astrophysics Data System (ADS)

    Neff, T.; Feldmeier, H.

    2008-05-01

    The Fermionic Molecular Dynamics (FMD) model uses Gaussian wave packets as single-particle states. Intrinsic many-body basis states are constructed as Slater determinants which have to be projected on parity, angular momentum and total linear momentum to restore the symmetries of the Hamiltonian. The flexibility of the Gaussian basis allows to economically describe states with shell structures as well as states featuring clustering or halos. We use an effective interaction that is derived from the realistic Argonne V18 interaction by means of the Unitary Correlation Operator Method (UCOM). A phenomenological momentum-dependent two-body correction simulates contributions from missing three-body forces and three-body correlations. We discuss 12C with a special emphasis on the structure of the excited 0+ and 2+ states. We analyze the degree of α-clustering and confirm, taking inelastic electron scattering data into account, the conjecture that the Hoyle state has to be understood as a loosely bound system of alpha particles. We will also present first results on the application of FMD for the calculation of scattering phase shifts in 3He — 4He.

  19. Functional hypothesis on miraculin' sweetness by a molecular dynamics approach.

    PubMed

    Paladino, Antonella; Colonna, Giovanni; Facchiano, Angelo M; Costantini, Susan

    2010-06-01

    Miraculin differs from other sweet-tasting proteins because it is a taste-modifier having the unusual property of modifying sourness into sweetness. Its dimer is covalently linked by an inter-chain disulphide bond, and shows its taste-modifying activity at acidic pH, with maximum at pH 3.0, while it is flat at neutral pH. Previous studies suggested the importance of two histidine residues for the taste-modifying activity of miraculin. In this work, we have conducted molecular dynamics simulations on wild type miraculin and on three mutated dimers (H29A, H59A and H29A/H59A) both at neutral and acidic pH to investigate the structural and functional role of these two His residues. Our results suggested that at acidic pH the presence of two charged His at the interface induced a structural rearrangement of the two monomers, thus leading to their relative opening and the following adaptation of their conformation to the receptor surface. On the other hand the simulations on three mutants showed that the mutated dimers had a closed form, and highlighted the important role of H29 in stabilizing/destabilizing the dimer arrangement and also a cooperative effect of the two histidines. PMID:20451498

  20. Molecular adjuvants and immunomodulators: new approaches to immunization.

    PubMed Central

    Johnson, A G

    1994-01-01

    Epitopes on microbial antigens responsible for protective immunity have begun to be identified and isolated, and their chemical structures have been determined. Ensuing knowledge of their weak immunizing capacity per se has led to an appreciation of the need for adjuvants to increase the immunogenicity of these low-molecular-weight synthetic structures. As such, a recent surge in adjuvant research has emerged. Accordingly, this review will highlight a number of those adjuvant substances whose activity in animals indicates a potential use in human vaccines. In addition, the potential of several well-defined substances, termed immunomodulators, which nonspecifically stimulate resistance of animals to multiple 50% lethal doses of microbial challenge is described. Among the most extensively characterized adjuvants of microbial origin discussed in detail are (i) the lipopolysaccharides isolated from gram-negative bacteria and their nontoxic analogs, (ii) the synthetic muramyl dipeptides and their multiple analogs, and (iii) the synthetic polyribonucleotide complexes, mimicking the interferon-inducing capacity of viruses. Discussed also are the heat-labile enterotoxin of Escherichia coli, the nonionic block copolymers, the saponins, a quinolamine derivative, and the hormone dihydroepiandrosterone. PMID:7923049

  1. Avian schistosomes in French aquatic birds: a molecular approach.

    PubMed

    Jouet, D; Ferté, H; Hologne, C; Kaltenbach, M L; Depaquit, J

    2009-06-01

    The prevalence of human cercarial dermatitis (HCD) caused by bird schistosomes appears to be increasing in France, in light of the impact of tourism combined with high densities of wild aquatic hosts in freshwater areas. The present work expands our knowledge of schistosome systematics by including samples of bird schistosomes collected from their natural hosts in France. Heads (318) and viscera (81) of aquatic birds belonging to 16 species from five orders, collecting during the hunting seasons or found dead, were autopsied for nasal and visceral schistosomes. Eggs and/or adults were analysed by molecular methods using the D2 domain and the second internal transcribed spacer (ITS-2) region of rDNA to determine species. Even if nasal eggs were polymorphic according to the host, all haplotypes were similar to that of Trichobilharzia regenti. Marked diversity of visceral species was observed. Final hosts under natural conditions were reported. For the first time, Trichobilharzia franki is reported in its natural bird hosts, Anas platyrhynchos, Anas crecca, Aythya fuligula and Cygnus olor. We also identified T. szidati in A. crecca and Anas clypeata. Bilharziella polonica was found in six species of aquatic birds, including Grus grus. This finding is the first record of bird schistosomes in this aquatic bird. Three new taxa of visceral schistosomes in Anser anser are strongly suspected according to their haplotypes. Futhermore, a new haplotype of visceral schistosomes isolated in Cygnus olor and similar to Allobilharzia visceralis was identified. PMID:19356266

  2. Molecular adjuvants and immunomodulators: new approaches to immunization.

    PubMed

    Johnson, A G

    1994-07-01

    Epitopes on microbial antigens responsible for protective immunity have begun to be identified and isolated, and their chemical structures have been determined. Ensuing knowledge of their weak immunizing capacity per se has led to an appreciation of the need for adjuvants to increase the immunogenicity of these low-molecular-weight synthetic structures. As such, a recent surge in adjuvant research has emerged. Accordingly, this review will highlight a number of those adjuvant substances whose activity in animals indicates a potential use in human vaccines. In addition, the potential of several well-defined substances, termed immunomodulators, which nonspecifically stimulate resistance of animals to multiple 50% lethal doses of microbial challenge is described. Among the most extensively characterized adjuvants of microbial origin discussed in detail are (i) the lipopolysaccharides isolated from gram-negative bacteria and their nontoxic analogs, (ii) the synthetic muramyl dipeptides and their multiple analogs, and (iii) the synthetic polyribonucleotide complexes, mimicking the interferon-inducing capacity of viruses. Discussed also are the heat-labile enterotoxin of Escherichia coli, the nonionic block copolymers, the saponins, a quinolamine derivative, and the hormone dihydroepiandrosterone. PMID:7923049

  3. Characterization of Sensory Properties of Flavanols - A Molecular Dynamic Approach.

    PubMed

    Ferrer-Gallego, Raúl; Quijada-Morín, Natalia; Brás, Natércia F; Gomes, Paula; de Freitas, Victor; Rivas-Gonzalo, Julián C; Escribano-Bailón, M Teresa

    2015-07-01

    In this work, sensations elicited by catechin and procyanidins in comparison with those elicited by gallocatechin and prodelphinidins were evaluated by means of a sensory panel. To obtain further insights into the mechanisms of action, molecular dynamics (MD) simulations and saturation transfer difference nuclear magnetic resonance (STD NMR) experiments have been performed. Results showed clear differences between the 2 types of flavanols. Dihydroxylated B-ring flavanols were more astringent, bitter, dry, rough, unripe, and persistent than trihydroxylated B-ring ones. Besides, these last compounds were smoother, more velvety, and viscous. MD simulations and STD NMR experiments support results obtained from tasting panel. MD results suggested that catechin binds to a human salivary proline-rich peptide IB714 faster than gallocatechin and this interaction is maintained longer. IB714 can interact with 2 catechin molecules concurrently while only interacts with 1 gallocatechin molecule. Accordingly, STD NMR experiments showed a greater affinity of catechin than gallocatechin for the peptide (K D = 2.7 and 25.7, respectively). Results indicate that the number of hydroxyl substituents present in B-ring of the flavanic nucleus is decisive for the interaction with salivary proteins and the development of astringency perception. PMID:25934978

  4. 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

  5. Systems Engineering Interfaces: A Model Based Approach

    NASA Technical Reports Server (NTRS)

    Fosse, Elyse; Delp, Christopher

    2013-01-01

    Currently: Ops Rev developed and maintains a framework that includes interface-specific language, patterns, and Viewpoints. Ops Rev implements the framework to design MOS 2.0 and its 5 Mission Services. Implementation de-couples interfaces and instances of interaction Future: A Mission MOSE implements the approach and uses the model based artifacts for reviews. The framework extends further into the ground data layers and provides a unified methodology.

  6. Dissecting the Critical Factors for Thermodynamic Stability of Modular Proteins Using Molecular Modeling Approach

    PubMed Central

    Lee, Sang-Chul; Han, Jieun; Heu, Woosung; Park, Keunwan; Kim, Hyun Jung; Cheong, Hae-Kap; Kim, Dongsup; Kim, Hak-Sung; Lee, Keun Woo

    2014-01-01

    Repeat proteins have recently attracted much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural and biophysical features. In particular, repeat proteins show high stability against temperature and chaotic agents. Despite many studies, structural features for the stability of repeat proteins remain poorly understood. Here we present an interesting result from in silico analyses pursuing the factors which affect the stability of repeat proteins. Previously developed repebody structure based on variable lymphocytes receptors (VLRs) which consists of leucine-rich repeat (LRR) modules was used as initial structure for the present study. We constructed extra six repebody structures with varying numbers of repeat modules and those structures were used for molecular dynamics simulations. For the structures, the intramolecular interactions including backbone H-bonds, van der Waals energy, and hydrophobicity were investigated and then the radius of gyration, solvent-accessible surface area, ratio of secondary structure, and hydration free energy were also calculated to find out the relationship between the number of LRR modules and stability of the protein. Our results show that the intramolecular interactions lead to more compact structure and smaller surface area of the repebodies, which are critical for the stability of repeat proteins. The other features were also well compatible with the experimental results. Based on our observations, the repebody-5 was proposed as the best structure from the all repebodies in structure optimization process. The present study successfully demonstrated that our computer-based molecular modeling approach can significantly contribute to the experiment-based protein engineering challenge. PMID:24849801

  7. ERα-Negative and Triple Negative Breast Cancer: Molecular Features and Potential Therapeutic Approaches

    PubMed Central

    Chen, Jin-Qiang; Russo, Jose

    2010-01-01

    Triple negative breast cancer (TNBC) is a type of aggressive breast cancer lacking the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER-2). TNBC patients account for approximately 15% of total breast cancer patients and are more prevalent among young African, African-American and Latino women patients. The currently available ER-targeted and Her-2-based therapies are not effective for treating TNBC. Recent studies have revealed a number of novel features of TNBC. In the present work, we comprehensively addressed these features and discussed potential therapeutic approaches based on these features for TNBC, with particular focus on: 1) the pathological features of TNBC/basal-like breast cancer; 2) E2/ERβ – mediated signaling pathways; 3) G-protein coupling receptor-30/epithelial growth factor receptor (GPCR-30/EGFR) signaling pathway; 4) interactions of ERβ with breast cancer 1/2 (BRCA1/2); 5) chemokine CXCL8 and related chemokines; 6) altered microRNA signatures and suppression of ERα expression/ERα-signaling by micro-RNAs; 7) altered expression of several pro-oncongenic and tumor suppressor proteins; and 8) genotoxic effects caused by oxidative estrogen metabolites. Gaining better insights into these molecular pathways in TNBC may lead to identification of novel biomarkers and targets for development of diagnostic and therapeutic approaches for prevention and treatment of TNBC. PMID:19527773

  8. Molecular Approach to Targeted Therapy for Multiple Sclerosis.

    PubMed

    Sherbet, Gajanan V

    2016-01-01

    The development and evolution of targeted therapy to any disease require the identification of targets amenable to treatment of patients. Here the pathogenetic signalling systems involved in multiple sclerosis are scrutinised to locate nodes of deregulation and dysfunction in order to devise strategies of drug development for targeted intervention. Oliogoclonal bands (OCB) are isoelectric focusing profiles of immunoglobulins synthesised in the central nervous system. OCBs enable the diagnosis of multiple sclerosis with high sensitivity and specificity and are related to the course of the disease and progression. The OCB patterns can be linked with the expression of angiogenic molecular species. Angiogenic signalling which has also been implicated in demyelination provides the option of using angiogenesis inhibitors in disease control. The PI3K (phosphoinositide 3-kinase)/Akt axis has emerged with a key role in myelination with its demonstrable links with mTOR mediated transcription of downstream target genes. Inflammatory signals and innate and acquired immunity from the activation of NF-κB (nuclear factor κB) responsive genes are considered. NF-κB signalling could be implicated in myelination. The transcription factor STAT (signal transducers and activators of transcription) and the EBV (Epstein- Barr virus) transcription factor BZLF1 contributing significantly to the disease process are a major environmental factor linked to MS. EBV can activate TGF (transforming growth factor) and VEGF (vascular endothelial growth factor) signalling. EBV microRNAs are reviewed as signalling mediators of pathogenesis. Stem cell transplantation therapy has lately gained much credence, so the current status of mesenchymal and hematopoietic stem cell therapy is reviewed with emphasis on the differential expression immune-related genes and operation of signalling systems. PMID:26560895

  9. Molecular approach to identify antidiabetic potential of Azadirachta indica

    PubMed Central

    Satyanarayana, K.; Sravanthi, K.; Shaker, I. Anand; Ponnulakshmi, R.

    2015-01-01

    Background: Azadirachta indica (Neem) is a medicinal plant, used in Ayurveda for treating various diseases, one of which is diabetes mellitus. It is known to possess antiinflammatory, antipyretic, antimicrobial, antidiabetic and diverse pharmacological properties. However, the molecular mechanism underlying the effect of A. indica on insulin signal transduction and glucose homeostasis is obscure. Objective: The aim was to study the effects of A. indica aqueous leaf extract on the expression of insulin signaling molecules and glucose oxidation in target tissue of high-fat and fructose-induced type-2 diabetic male rat. Materials and Methods: The oral effective dose of A. indica leaf extract (400 mg/kg body weight [b.wt]) was given once daily for 30 days to high-fat diet-induced diabetic rats. At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose oxidation in gastrocnemius muscle were assessed. Results: Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (insulin receptor, insulin receptor substrate-1, phospho-IRS-1Tyr632, phospho-IRS-1Ser636, phospho-AktSer473, and glucose transporter 4 [GLUT4] proteins), glycogen concentration and glucose oxidation. The treatment with A. indica leaf extract normalized the altered levels of blood glucose, serum insulin, lipid profile and insulin signaling molecules as well as GLUT4 proteins at 400 mg/kg b.wt dose. Conclusion: It is concluded from the present study that A. indica may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle. PMID:26604551

  10. Stochastic approach to the molecular counting problem in superresolution microscopy

    PubMed Central

    Rollins, Geoffrey C.; Shin, Jae Yen; Bustamante, Carlos; Pressé, Steve

    2015-01-01

    Superresolution imaging methods—now widely used to characterize biological structures below the diffraction limit—are poised to reveal in quantitative detail the stoichiometry of protein complexes in living cells. In practice, the photophysical properties of the fluorophores used as tags in superresolution methods have posed a severe theoretical challenge toward achieving this goal. Here we develop a stochastic approach to enumerate fluorophores in a diffraction-limited area measured by superresolution microscopy. The method is a generalization of aggregated Markov methods developed in the ion channel literature for studying gating dynamics. We show that the method accurately and precisely enumerates fluorophores in simulated data while simultaneously determining the kinetic rates that govern the stochastic photophysics of the fluorophores to improve the prediction’s accuracy. This stochastic method overcomes several critical limitations of temporal thresholding methods. PMID:25535361

  11. Regulation of gene expression by hypoxia: a molecular approach.

    PubMed

    Beitner-Johnson, D; Shull, G E; Dedman, J R; Millhorn, D E

    1997-11-01

    Oxygen is a strict requirement for cell function. The cellular mechanisms by which organisms detect and respond to changes in oxygen tension remain a major unanswered question in pulmonary physiology. Part of the difficulty in addressing this question is due to the limited scope of experiments that can be performed in vivo. In the past few years, several laboratories have begun to make progress in this area, using a variety of cell culture model systems and sophisticated genetic manipulations. Here, we review the current state of knowledge of regulation of gene expression by hypoxia, and describe novel experimental approaches that promise to broaden our understanding of how cells and whole organisms respond to alterations in O2 tension. PMID:9407603

  12. A microfabrication-based approach to quantitative isothermal titration calorimetry.

    PubMed

    Wang, Bin; Jia, Yuan; Lin, Qiao

    2016-04-15

    Isothermal titration calorimetry (ITC) directly measures heat evolved in a chemical reaction to determine equilibrium binding properties of biomolecular systems. Conventional ITC instruments are expensive, use complicated design and construction, and require long analysis times. Microfabricated calorimetric devices are promising, although they have yet to allow accurate, quantitative ITC measurements of biochemical reactions. This paper presents a microfabrication-based approach to integrated, quantitative ITC characterization of biomolecular interactions. The approach integrates microfabricated differential calorimetric sensors with microfluidic titration. Biomolecules and reagents are introduced at each of a series of molar ratios, mixed, and allowed to react. The reaction thermal power is differentially measured, and used to determine the thermodynamic profile of the biomolecular interactions. Implemented in a microdevice featuring thermally isolated, well-defined reaction volumes with minimized fluid evaporation as well as highly sensitive thermoelectric sensing, the approach enables accurate and quantitative ITC measurements of protein-ligand interactions under different isothermal conditions. Using the approach, we demonstrate ITC characterization of the binding of 18-Crown-6 with barium chloride, and the binding of ribonuclease A with cytidine 2'-monophosphate within reaction volumes of approximately 0.7 µL and at concentrations down to 2mM. For each binding system, the ITC measurements were completed with considerably reduced analysis times and material consumption, and yielded a complete thermodynamic profile of the molecular interaction in agreement with published data. This demonstrates the potential usefulness of our approach for biomolecular characterization in biomedical applications. PMID:26655185

  13. MOLECULAR DIVERSITY OF DRINKING WATER MICROBIAL COMMUNITIES: A PHYLOGENETIC APPROACH

    EPA Science Inventory

    The microbiological quality of drinking water is assessed using culture-based methods that are highly selective and that tend to underestimate the densities and diversity of microbial populations inhabiting distribution systems. In order to better understand the effect of differe...

  14. Molecular Dynamics Approach for Predicting Helical Twisting Powers of Metal Complex Dopants in Nematic Solvents.

    PubMed

    Watanabe, Go; Yoshida, Jun

    2016-07-14

    Nematic liquid crystals of small molecules are known to transform into chiral nematic liquid crystals with supramolecular helical structures upon doping with enantiomeric compounds. Although this phenomenon is well established, the basic mechanism is still unclear. We have previously examined metal complexes with Δ and Λ chiralities as dopants in nematic liquid crystals and have found that slight differences in the molecular structure determine the handedness of the induced helical structure. In this study, we investigated the microscopic arrangement of liquid crystal molecules around metal complex dopants with the aid of molecular dynamics (MD) simulations. There are several restrictions to performing MD simulations of the chiral nematic system; for example, one pitch of the helix usually exceeds one side of an applicable periodic boundary box (∼10(2) nm). In view of these simulation problems, we therefore examined racemic systems in which a pair of Δ- and Λ-isomers of the chiral dopant is mixed with liquid crystal molecules. We selected two different octahedral ruthenium complexes as the chiral dopant molecules. As a result, we accurately calculated the ordering matrix that is essential parameter to estimate the helical twisting power of the chiral dopant based on the surface chirality model. Since the microscopic ordering is experimentally hard to be determined, our new approach with using MD simulations accurately deduced the ordering matrix and, with the aid of the surface chirality model, gave reasonable values for the helical twisting powers of each complex. PMID:27333445

  15. Microfabricated cantilever-based detector for molecular beam experiments

    NASA Astrophysics Data System (ADS)

    Bachels, T.; Schäfer, R.

    1998-11-01

    A low cost detector for particles in molecular beam experiments is presented which can easily be mounted in a molecular beam apparatus. The detector is based on microfabricated cantilevers, which can be employed either as single sensors or as sensor arrays. The single cantilever technique has been used to measure the absolute number of atoms coming out of a pulsed laser vaporization cluster source. The particles are detected by the shift of the thermally excited resonance frequency of the cantilever due to the cluster deposition. We have determined with the single cantilever the ratio of neutral to ionized clusters and we have investigated the cluster generation at different source conditions. In addition to this, a microfabricated cantilever array has been used to measure molecular beam profiles, which opens new possibilities for molecular beam deflection experiments.

  16. Molecular Approaches to Understanding C & N Dynamics in MArine Sediments

    SciTech Connect

    Arturo Massol; James Tiedje; Jizhong Zhou; Allan Devol

    2007-05-16

    Continental margin sediments constitute only about 10% of the total sediment surface area in the world’s oceans, nevertheless they are the dominant sites of nitrogen (N) cycling. Recent studies suggest that the oceanic nitrogen budget is unbalanced, primarily due to a higher nitrogen removal rate in contrast to the fixation rate, and it has been suggested that denitrification activity contributes significantly to this imbalance. Although denitrification in marine environments has been studied intensively at the process level, little is known about the species abundance, composition, distribution, and functional differences of the denitrifying population. Understanding the diversity of microbial populations in marine environments, their responses to various environmental factors such as NO3-, and how this impact the rate of denitrification is critical to predict global N dynamics. Environmental Microbiology has the prompt to study the influence of each microbial population on a biogeochemical process within a given ecosystem. Culture-dependent and –independent techniques using nucleic acid probes can access the identity and activity of cultured and uncultured microorganisms. Nucleic acid probes can target distintict genes which set phylogenetic relationships, such as rDNA 16S, DNA gyrase (gyrB) and RNA polymerase sigma 70 factor (rpoD). In the other hand, the genetic capabilities and their expression could be tracked using probes that target several functional genes, such as nirS, nirK, nosZ, and nifH, which are genes involved in denitrification. Selective detection of cells actively expressing functional genes within a community using In Situ Reverse Transcription-PCR (ISRT-PCR) could become a powerful culture-independent technique in microbial ecology. Here we describe an approach to study the expression of nirS genes in denitrifying bacteria. Pure cultures of Pseudomonas stutzeri and Paracoccus denitrificans, as well as co-cultures with non

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

    PubMed Central

    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

    2015-01-01

    Background: 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. Methods: 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. Results: 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. Conclusions: Molecular classification of ECs can be achieved using clinically applicable methods on formalin-fixed paraffin-embedded samples, and provides

  18. MOLECULAR IMAGING OF PROSTATE CANCER: translating molecular biology approaches into the clinical realm

    PubMed Central

    Vargas, Hebert Alberto; Grimm, Jan; Donati, Olivio F.; Sala, Evis; Hricak, Hedvig

    2016-01-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980’s. Most prostate cancers today are detected at early stages of the disease and are considered “indolent”, however some patients’ prostate cancers demonstrate a more aggressive behavior which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterizes this disease has lead to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumor detection alone to distinguishing patients with indolent tumors that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumors that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualization of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. PMID:25693661

  19. Induced base transistor fabricated by molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Chang, C.-Y.; Liu, W. C.; Jame, M. S.; Wang, Y. H.; Luryi, S.

    1986-09-01

    A novel three-terminal hot-electron device, the induced base transistor (IBT), has been fabricated by molecular beam epitaxy. Two-dimensional electron gas induced by the applied collector field in an undoped GaAs quantum well is used as the base of the IBT. The common-base current gain alpha has been achieved as high as 0.96 under a collector bias of 2.5 V and an emitter current of 3 mA.

  20. Heutagogy: An alternative practice based learning approach.

    PubMed

    Bhoyrub, John; Hurley, John; Neilson, Gavin R; Ramsay, Mike; Smith, Margaret

    2010-11-01

    Education has explored and utilised multiple approaches in attempts to enhance the learning and teaching opportunities available to adult learners. Traditional pedagogy has been both directly and indirectly affected by andragogy and transformational learning, consequently widening our understandings and approaches toward view teaching and learning. Within the context of nurse education, a major challenge has been to effectively apply these educational approaches to the complex, unpredictable and challenging environment of practice based learning. While not offered as a panacea to such challenges, heutagogy is offered in this discussion paper as an emerging and potentially highly congruent educational framework to place around practice based learning. Being an emergent theory its known conceptual underpinnings and possible applications to nurse education need to be explored and theoretically applied. Through placing the adult learner at the foreground of grasping learning opportunities as they unpredictability emerge from a sometimes chaotic environment, heutagogy can be argued as offering the potential to minimise many of the well published difficulties of coordinating practice with faculty teaching and learning. PMID:20554249

  1. Molecular Approaches To Target GPCRs in Cancer Therapy

    PubMed Central

    Innamorati, Giulio; Valenti, Maria Teresa; Giovinazzo, Francesco; Carbonare, Luca Dalle; Parenti, Marco; Bassi, Claudio

    2011-01-01

    Hundreds of G protein coupled receptor (GPCR) isotypes integrate and coordinate the function of individual cells mediating signaling between different organs in our bodies. As an aberration of the normal relationships that organize cells' coexistence, cancer has to deceive cell-cell communication in order to grow and spread. GPCRs play a critical role in this process. Despite the fact that GPCRs represent one of the most common drug targets, current medical practice includes only a few anticancer compounds directly acting on their signaling. Many approaches can be envisaged to target GPCRs involved in oncology. Beyond interfering with GPCRs signaling by using agonists or antagonists to prevent cell proliferation, favor apoptosis, induce maturation, prevent migration, etc., the high specificity of the interaction between the receptors and their ligands can be exploited to deliver toxins, antineoplastic drugs or isotopes to transformed cells. In this review we describe the strategies that are in use, or appear promising, to act directly on GPCRs in the fight against neoplastic transformation and tumor progression.

  2. Mitohormesis in muscle cells: a morphological, molecular, and proteomic approach

    PubMed Central

    Barbieri, Elena; Sestili, Piero; Vallorani, Luciana; Guescini, Michele; Calcabrini, Cinzia; Gioacchini, Anna Maria; Annibalini, Giosuè; Lucertini, Francesco; Piccoli, Giovanni; Stocchi, Vilberto

    2013-01-01

    Summary Low-level oxidative stress induces an adaptive response commonly defined as hormesis; this type of stress is often related to reactive oxygen species (ROS) originating from the mitochondrial respiratory chain (mitochondrial hormesis or mitohormesis). The accumulation of transient low doses of ROS either through chronic physical activity or caloric restriction influences signaling from the mitochondrial compartment to the cell, reduces glucose metabolism, induces mitochondrial metabolism, increases stress resistance and ultimately, increases lifespan. Mitochondrial formation of presumably harmful levels (chronic and/or excessive) of ROS within skeletal muscle has been observed in insulin resistance of obese subjects, type 2 diabetes mellitus, as well as in impaired muscle function associated with normal aging. Advances in mitochondrial bioimaging combined with mitochondrial biochemistry and proteome research have broadened our knowledge of specific cellular signaling and other related functions of the mitochondrial behavior. In this review, we describe mitochondrial remodeling in response to different degrees of oxidative insults induced in vitro in myocytes and in vivo in skeletal muscle, focusing on the potential application of a combined morphological and biochemical approach. The use of such technologies could yield benefits for our overall understanding of physiology for biotechnological research related to drug design, physical activity prescription and significant lifestyle changes. PMID:24596688

  3. Hybrid Coupled Cluster and Molecular Dynamics Approach: Application to the Excitation Spectrum of Cytosine in the Native DNA Environment

    SciTech Connect

    Valiev, Marat; Kowalski, Karol

    2006-12-07

    Evolution of the excited state energies of cytosine base in the native DNA environment was investigated using hybrid coupled cluster and classical molecular dynamics approach. The time averaged excitation energies obtained with the variant of the completely renormalized equation-of-motion with singles, doubles, and non-iterative triples approach that includes a bulk of the correlation effects for excited states, are compared with the analogous calculations in the gas phase. Significant blue shifts for the two lowest singlet excitation energies can be observed as a result of interaction of the quantum system with surrounding environment.

  4. 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

  5. Practical Approaches for Mining Frequent Patterns in Molecular Datasets.

    PubMed

    Naulaerts, Stefan; Moens, Sandy; Engelen, Kristof; Berghe, Wim Vanden; Goethals, Bart; Laukens, Kris; Meysman, Pieter

    2016-01-01

    Pattern detection is an inherent task in the analysis and interpretation of complex and continuously accumulating biological data. Numerous itemset mining algorithms have been developed in the last decade to efficiently detect specific pattern classes in data. Although many of these have proven their value for addressing bioinformatics problems, several factors still slow down promising algorithms from gaining popularity in the life science community. Many of these issues stem from the low user-friendliness of these tools and the complexity of their output, which is often large, static, and consequently hard to interpret. Here, we apply three software implementations on common bioinformatics problems and illustrate some of the advantages and disadvantages of each, as well as inherent pitfalls of biological data mining. Frequent itemset mining exists in many different flavors, and users should decide their software choice based on their research question, programming proficiency, and added value of extra features. PMID:27168722

  6. Practical Approaches for Mining Frequent Patterns in Molecular Datasets

    PubMed Central

    Naulaerts, Stefan; Moens, Sandy; Engelen, Kristof; Berghe, Wim Vanden; Goethals, Bart; Laukens, Kris; Meysman, Pieter

    2016-01-01

    Pattern detection is an inherent task in the analysis and interpretation of complex and continuously accumulating biological data. Numerous itemset mining algorithms have been developed in the last decade to efficiently detect specific pattern classes in data. Although many of these have proven their value for addressing bioinformatics problems, several factors still slow down promising algorithms from gaining popularity in the life science community. Many of these issues stem from the low user-friendliness of these tools and the complexity of their output, which is often large, static, and consequently hard to interpret. Here, we apply three software implementations on common bioinformatics problems and illustrate some of the advantages and disadvantages of each, as well as inherent pitfalls of biological data mining. Frequent itemset mining exists in many different flavors, and users should decide their software choice based on their research question, programming proficiency, and added value of extra features. PMID:27168722

  7. A novel logic-based approach for quantitative toxicology prediction.

    PubMed

    Amini, Ata; Muggleton, Stephen H; Lodhi, Huma; Sternberg, Michael J E

    2007-01-01

    There is a pressing need for accurate in silico methods to predict the toxicity of molecules that are being introduced into the environment or are being developed into new pharmaceuticals. Predictive toxicology is in the realm of structure activity relationships (SAR), and many approaches have been used to derive such SAR. Previous work has shown that inductive logic programming (ILP) is a powerful approach that circumvents several major difficulties, such as molecular superposition, faced by some other SAR methods. The ILP approach reasons with chemical substructures within a relational framework and yields chemically understandable rules. Here, we report a general new approach, support vector inductive logic programming (SVILP), which extends the essentially qualitative ILP-based SAR to quantitative modeling. First, ILP is used to learn rules, the predictions of which are then used within a novel kernel to derive a support-vector generalization model. For a highly heterogeneous dataset of 576 molecules with known fathead minnow fish toxicity, the cross-validated correlation coefficients (R2CV) from a chemical descriptor method (CHEM) and SVILP are 0.52 and 0.66, respectively. The ILP, CHEM, and SVILP approaches correctly predict 55, 58, and 73%, respectively, of toxic molecules. In a set of 165 unseen molecules, the R2 values from the commercial software TOPKAT and SVILP are 0.26 and 0.57, respectively. In all calculations, SVILP showed significant improvements in comparison with the other methods. The SVILP approach has a major advantage in that it uses ILP automatically and consistently to derive rules, mostly novel, describing fragments that are toxicity alerts. The SVILP is a general machine-learning approach and has the potential of tackling many problems relevant to chemoinformatics including in silico drug design. PMID:17451225

  8. 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.

  9. Molecular tailoring approach for geometry optimization of large molecules: Energy evaluation and parallelization strategies

    NASA Astrophysics Data System (ADS)

    Ganesh, V.; Dongare, Rameshwar K.; Balanarayan, P.; Gadre, Shridhar R.

    2006-09-01

    A linear-scaling scheme for estimating the electronic energy, gradients, and Hessian of a large molecule at ab initio level of theory based on fragment set cardinality is presented. With this proposition, a general, cardinality-guided molecular tailoring approach (CG-MTA) for ab initio geometry optimization of large molecules is implemented. The method employs energy gradients extracted from fragment wave functions, enabling computations otherwise impractical on PC hardware. Further, the method is readily amenable to large scale coarse-grain parallelization with minimal communication among nodes, resulting in a near-linear speedup. CG-MTA is applied for density-functional-theory-based geometry optimization of a variety of molecules including α-tocopherol, taxol, γ-cyclodextrin, and two conformations of polyglycine. In the tests performed, energy and gradient estimates obtained from CG-MTA during optimization runs show an excellent agreement with those obtained from actual computation. Accuracy of the Hessian obtained employing CG-MTA provides good hope for the application of Hessian-based geometry optimization to large molecules.

  10. Predicting activity approach based on new atoms similarity kernel function.

    PubMed

    Abu El-Atta, Ahmed H; Moussa, M I; Hassanien, Aboul Ella

    2015-07-01

    Drug design is a high cost and long term process. To reduce time and costs for drugs discoveries, new techniques are needed. Chemoinformatics field implements the informational techniques and computer science like machine learning and graph theory to discover the chemical compounds properties, such as toxicity or biological activity. This is done through analyzing their molecular structure (molecular graph). To overcome this problem there is an increasing need for algorithms to analyze and classify graph data to predict the activity of molecules. Kernels methods provide a powerful framework which combines machine learning with graph theory techniques. These kernels methods have led to impressive performance results in many several chemoinformatics problems like biological activity prediction. This paper presents a new approach based on kernel functions to solve activity prediction problem for chemical compounds. First we encode all atoms depending on their neighbors then we use these codes to find a relationship between those atoms each other. Then we use relation between different atoms to find similarity between chemical compounds. The proposed approach was compared with many other classification methods and the results show competitive accuracy with these methods. PMID:26117822

  11. Electrospinning of peptide and protein fibres: approaching the molecular scale.

    PubMed

    Nuansing, Wiwat; Frauchiger, Daniela; Huth, Florian; Rebollo, Amaia; Hillenbrand, Rainer; Bittner, Alexander M

    2013-01-01

    For the example of peptides and proteins, we contrast "natural" self-assembly, i.e. aggregation in solutions, with "forced" assembly by electrospinning, i.e. by application of strong electrical fields to concentrated solutions. We were able to spin fibres that contain short stretches of diameters down to 5 nm; the ultimate aim is a fibre of the size of a single molecule. Besides their wide biochemical relevance, small peptides can assemble to defined supramolecular structures such as fibres and tubes. While the main driving mechanism in electrospinning is certainly based on electrostatics, aromatic groups in peptides might play a directing role. We used fluorenyl and phenyl, whose i-stacking is not manifested in vibrational spectra, but is clearly visible in their crystal structures. The main differences between solid phases and single molecules are found for O-H and N-H stretching and bending vibrations, due to extensive hydrogen bonding in solids. However, we found that only proteins, but not peptides, can be spun into ultrathin fibres. Therefore, nanoscale analysis by SEM and AFM, and by infrared near-field microscopy are especially useful. The comparison of the amide bands from the infrared and Raman spectra, combined with circular dichroism spectroscopy, allowed us to assign secondary structures. Our results are not only useful for interpreting and refining current theories of self-assembly and electrospinning, but also for creating new scaffolds for the growth of sensitive cells. PMID:24611278

  12. Molecular and systems approaches towards drought-tolerant canola crops.

    PubMed

    Zhu, Mengmeng; Monroe, J Grey; Suhail, Yasir; Villiers, Florent; Mullen, Jack; Pater, Dianne; Hauser, Felix; Jeon, Byeong Wook; Bader, Joel S; Kwak, June M; Schroeder, Julian I; McKay, John K; Assmann, Sarah M

    2016-06-01

    1169 I. 1170 II. 1170 III. 1172 IV. 1176 V. 1181 VI. 1182 1183 References 1183 SUMMARY: Modern agriculture is facing multiple challenges including the necessity for a substantial increase in production to meet the needs of a burgeoning human population. Water shortage is a deleterious consequence of both population growth and climate change and is one of the most severe factors limiting global crop productivity. Brassica species, particularly canola varieties, are cultivated worldwide for edible oil, animal feed, and biodiesel, and suffer dramatic yield loss upon drought stress. The recent release of the Brassica napus genome supplies essential genetic information to facilitate identification of drought-related genes and provides new information for agricultural improvement in this species. Here we summarize current knowledge regarding drought responses of canola, including physiological and -omics effects of drought. We further discuss knowledge gained through translational biology based on discoveries in the closely related reference species Arabidopsis thaliana and through genetic strategies such as genome-wide association studies and analysis of natural variation. Knowledge of drought tolerance/resistance responses in canola together with research outcomes arising from new technologies and methodologies will inform novel strategies for improvement of drought tolerance and yield in this and other important crop species. PMID:26879345

  13. A proteomics approach to decipher the molecular nature of planarian stem cells

    PubMed Central

    2011-01-01

    Background In recent years, planaria have emerged as an important model system for research into stem cells and regeneration. Attention is focused on their unique stem cells, the neoblasts, which can differentiate into any cell type present in the adult organism. Sequencing of the Schmidtea mediterranea genome and some expressed sequence tag projects have generated extensive data on the genetic profile of these cells. However, little information is available on their protein dynamics. Results We developed a proteomic strategy to identify neoblast-specific proteins. Here we describe the method and discuss the results in comparison to the genomic high-throughput analyses carried out in planaria and to proteomic studies using other stem cell systems. We also show functional data for some of the candidate genes selected in our proteomic approach. Conclusions We have developed an accurate and reliable mass-spectra-based proteomics approach to complement previous genomic studies and to further achieve a more accurate understanding and description of the molecular and cellular processes related to the neoblasts. PMID:21356107

  14. 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…

  15. Molecular Probe Data Base: a database on synthetic oligonucleotides.

    PubMed Central

    Romano, P; Aresu, O; Parodi, B; Manniello, A; Campi, G; Angelini, G; Romani, M; Iannotta, B; Rondanina, G; Ruzzon, T

    1993-01-01

    The Molecular Probe Data Base (MPDB) was designed to collect and make information on synthetic oligonucleotides available on-line. This paper briefly describes its purpose, contents and structure, forms and mode of data distribution. Particular emphasis is given to recent data extension and system enhancements that have been carried out in order to simplify access to MPDB for unskilled users. PMID:8332523

  16. 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…

  17. Exploring host-guest complexation mechanisms by a molecular dynamics/quantum mechanics/continuum solvent model approach

    NASA Astrophysics Data System (ADS)

    Ye, Renlong; Nie, Xuemei; Zhou, Yumei; Wong, Chung F.; Gong, Xuedong; Jiang, Wei; Tang, Weihua; Wang, Yan A.; Heine, Thomas; Zhou, Baojing

    2016-03-01

    We introduce a molecular dynamics/quantum mechanics/continuum solvent model (MD/QM/CSM) approach to investigate binding mechanisms of host-guest systems. The representative conformations of host, guest, and their complex generated from MD simulations at the molecular-mechanics level are used for binding free energy calculations based on a QM/CSM model. We use this approach to explore the binding mechanisms of β-cyclodextrin (β-CD) and 2, 6-di-methyl-β-CD (DM-β-CD) with various guest molecules. Our results suggest that solvent effects play a more important role in determining the relative binding affinities of DM-β-CD than those of β-CD mainly because the former is more flexible than the latter.

  18. Lunar base CELSS: A bioregenerative approach

    NASA Technical Reports Server (NTRS)

    Easterwood, G. W.; Street, J. J.; Sartain, J. B.; Hubbell, D. H.; Robitaille, H. A.

    1992-01-01

    During the twenty-first century, human habitation of a self-sustaining lunar base could become a reality. To achieve this goal, the occupants will have to have food, water, and an adequate atmosphere within a carefully designed environment. Advanced technology will be employed to support terrestrial life-sustaining processes on the Moon. One approach to a life support system based on food production, waste management and utilization, and product synthesis is outlined. Inputs include an atmosphere, water, plants, biodegradable substrates, and manufacutured materials such as fiberglass containment vessels from lunar resources. Outputs include purification of air and water, food, and hydrogen (H2) generated from methane (CH4). Important criteria are as follows: (1) minimize resupply from Earth; and (2) recycle as efficiently as possible.

  19. An Ontology Based Approach to Information Security

    NASA Astrophysics Data System (ADS)

    Pereira, Teresa; Santos, Henrique

    The semantically structure of knowledge, based on ontology approaches have been increasingly adopted by several expertise from diverse domains. Recently ontologies have been moved from the philosophical and metaphysics disciplines to be used in the construction of models to describe a specific theory of a domain. The development and the use of ontologies promote the creation of a unique standard to represent concepts within a specific knowledge domain. In the scope of information security systems the use of an ontology to formalize and represent the concepts of security information challenge the mechanisms and techniques currently used. This paper intends to present a conceptual implementation model of an ontology defined in the security domain. The model presented contains the semantic concepts based on the information security standard ISO/IEC_JTC1, and their relationships to other concepts, defined in a subset of the information security domain.

  20. LP based approach to optimal stable matchings

    SciTech Connect

    Teo, Chung-Piaw; Sethuraman, J.

    1997-06-01

    We study the classical stable marriage and stable roommates problems using a polyhedral approach. We propose a new LP formulation for the stable roommates problem. This formulation is non-empty if and only if the underlying roommates problem has a stable matching. Furthermore, for certain special weight functions on the edges, we construct a 2-approximation algorithm for the optimal stable roommates problem. Our technique uses a crucial geometry of the fractional solutions in this formulation. For the stable marriage problem, we show that a related geometry allows us to express any fractional solution in the stable marriage polytope as convex combination of stable marriage solutions. This leads to a genuinely simple proof of the integrality of the stable marriage polytope. Based on these ideas, we devise a heuristic to solve the optimal stable roommates problem. The heuristic combines the power of rounding and cutting-plane methods. We present some computational results based on preliminary implementations of this heuristic.

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

    PubMed

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

    2010-11-01

    Today's large-scale poultry production with densely stocked and enclosed production buildings is often accompanied by very high concentrations of airborne microorganisms leading to a clear health hazard for employees working in such environments. Depending on the expected exposure to microorganisms, work has to be performed under occupational safety conditions. In this study, turkey houses bioaerosols were investigated by cultivation-based and molecular methods in parallel to determine the concentrations and the composition of bacterial community. Results obtained with the molecular approach showed clearly its applicability for qualitative exposure measurements. With both, cultivation-based and molecular methods species of microorganism with a potential health risk for employees (Acinetobacter johnsonii, Aerococcus viridans, Pantoea agglomerans, and Shigella flexneri) were identified. These results underline the necessity of adequate protection measures, including the recommendation to wear breathing masks during work in poultry houses. PMID:20720091

  2. 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.

  3. Atomic Spectral Methods for Ab Initio Molecular Electronic Energy Surfaces: Transitioning From Small-Molecule to Biomolecular-Suitable Approaches.

    PubMed

    Mills, Jeffrey D; Ben-Nun, Michal; Rollin, Kyle; Bromley, Michael W J; Li, Jiabo; Hinde, Robert J; Winstead, Carl L; Sheehy, Jeffrey A; Boatz, Jerry A; Langhoff, Peter W

    2016-08-25

    Continuing attention has addressed incorportation of the electronically dynamical attributes of biomolecules in the largely static first-generation molecular-mechanical force fields commonly employed in molecular-dynamics simulations. We describe here a universal quantum-mechanical approach to calculations of the electronic energy surfaces of both small molecules and large aggregates on a common basis which can include such electronic attributes, and which also seems well-suited to adaptation in ab initio molecular-dynamics applications. In contrast to the more familiar orbital-product-based methodologies employed in traditional small-molecule computational quantum chemistry, the present approach is based on an "ex-post-facto" method in which Hamiltonian matrices are evaluated prior to wave function antisymmetrization, implemented here in the support of a Hilbert space of orthonormal products of many-electron atomic spectral eigenstates familiar from the van der Waals theory of long-range interactions. The general theory in its various forms incorporates the early semiempirical atoms- and diatomics-in-molecules approaches of Moffitt, Ellison, Tully, Kuntz, and others in a comprehensive mathematical setting, and generalizes the developments of Eisenschitz, London, Claverie, and others addressing electron permutation symmetry adaptation issues, completing these early attempts to treat van der Waals and chemical forces on a common basis. Exact expressions are obtained for molecular Hamiltonian matrices and for associated energy eigenvalues as sums of separate atomic and interaction-energy terms, similar in this respect to the forms of classical force fields. The latter representation is seen to also provide a long-missing general definition of the energies of individual atoms and of their interactions within molecules and matter free from subjective additional constraints. A computer code suite is described for calculations of the many-electron atomic eigenspectra and

  4. Synthetic aperture elastography: a GPU based approach

    NASA Astrophysics Data System (ADS)

    Verma, Prashant; Doyley, Marvin M.

    2014-03-01

    Synthetic aperture (SA) ultrasound imaging system produces highly accurate axial and lateral displacement estimates; however, low frame rates and large data volumes can hamper its clinical use. This paper describes a real-time SA imaging based ultrasound elastography system that we have recently developed to overcome this limitation. In this system, we implemented both beamforming and 2D cross-correlation echo tracking on Nvidia GTX 480 graphics processing unit (GPU). We used one thread per pixel for beamforming; whereas, one block per pixel was used for echo tracking. We compared the quality of elastograms computed with our real-time system relative to those computed using our standard single threaded elastographic imaging methodology. In all studies, we used conventional measures of image quality such as elastographic signal to noise ratio (SNRe). Specifically, SNRe of axial and lateral strain elastograms computed with real-time system were 36 dB and 23 dB, respectively, which was numerically equal to those computed with our standard approach. We achieved a frame rate of 6 frames per second using our GPU based approach for 16 transmits and kernel size of 60 × 60 pixels, which is 400 times faster than that achieved using our standard protocol.

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

    PubMed

    Van Dyck, Colin; Ratner, Mark A

    2015-03-11

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

  6. Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

    NASA Astrophysics Data System (ADS)

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

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

  7. 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.

  8. Microchip-based Devices for Molecular Diagnosis of Genetic Diseases.

    PubMed

    Cheng; Fortina; Surrey; Kricka; Wilding

    1996-09-01

    Microchips, constructed with a variety of microfabrication technologies (photolithography, micropatterning, microjet printing, light-directed chemical synthesis, laser stereochemical etching, and microcontact printing) are being applied to molecular biology. The new microchip-based analytical devices promise to solve the analytical problems faced by many molecular biologists (eg, contamination, low throughput, and high cost). They may revolutionize molecular biology and its application in clinical medicine, forensic science, and environmental monitoring. A typical biochemical analysis involves three main steps: (1) sample preparation, (2) biochemical reaction, and (3) detection (either separation or hybridization may be involved) accompanied by data acquisition and interpretation. The construction of a miniturized analyzer will therefore necessarily entail the miniaturization and integration of all three of these processes. The literature related to the miniaturization of these three processes indicates that the greatest emphasis so far is on the investigation and development of methods for the detection of nucleic acid, followed by the optimization of a biochemical reaction, such as the polymerase chain reaction. The first step involving sample preparation has received little attention. In this review the state of the art of, microchip-based, miniaturized analytical processes (eg, sample preparation, biochemical reaction, and detection of products) are outlined and the applications of microchip-based devices in the molecular diagnosis of genetic diseases are discussed. PMID:10462559

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

    PubMed

    Guo, Jing; Yang, Renqiang

    2012-03-01

    Design of elementary molecular logic gates is the key and the fundamental of performing complicated Boolean calculations. Herein, we report a strategy for constructing a DNA-based OR gate by using the mechanism of sequence recognition and the principle of fluorescence resonance energy transfer (FRET). In this system, the gate is entirely composed of a single strand of DNA (A, B and C) and the inputs are the molecular beacon probes (MB1 and MB2). Changes in fluorescence intensity confirm the realization of the OR logic operation and electrophoresis experiments verify these results. Our successful application of DNA to perform the binary operation represents that DNA can serve as an efficient biomaterial for designing molecular logic gates and devices. PMID:22278176

  10. 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.

  11. 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.

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

    PubMed

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

    2015-01-01

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

  13. Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

    PubMed Central

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

    2014-01-01

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

  14. 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. PMID:26203667

  15. Assessment of Genetic and Molecular Approaches for the Prediction of Wheat Quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of genetic and molecular approaches for the prediction of wheat quality. R.A. Graybosch, USDA-ARS, Lincoln, NE, U.S.A. Over the past four decades, the field of plant breeding and genetics has been revolutionized by technological advances in the areas of DNA manipulation and evaluation. Fo...

  16. A Novel Pictorial Approach to Teaching Molecular Motions in Polyatomic Molecules.

    ERIC Educational Resources Information Center

    Verkade, John G.

    1987-01-01

    Describes a procedure for teaching the "generator orbital" (GO) approach of molecular orbital bonding in polyatomic molecules. Explains how the GO can be utilized with students in generating the vibrational, rotational, and translational modes of molecules in a completely pictorial manner. (ML)

  17. EMERGING MOLECULAR AND COMPUTATIONAL APPROACHES FOR CROSS-SPECIES EXTRAPLATIONS: A WORKSHOP SUMMARY REPORT

    EPA Science Inventory

    Benson, W.H., R.T. Di Giulio, J.C. Cook, J. Freedman, R.L. Malek, C. Thompson and D. Versteeg. In press. Emerging Molecular and Computational Approaches for Cross-Species Extrapolations: A Workshop Summary Report (Abstract). To be presented at the SETAC Fourth World Congress, 14-...

  18. Peptide Based Radiopharmaceuticals: Specific Construct Approach

    SciTech Connect

    Som, P; Rhodes, B A; Sharma, S S

    1997-10-21

    The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures). In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays

  19. ECG biometric identification: A compression based approach.

    PubMed

    Bras, Susana; Pinho, Armando J

    2015-08-01

    Using the electrocardiogram signal (ECG) to identify and/or authenticate persons are problems still lacking satisfactory solutions. Yet, ECG possesses characteristics that are unique or difficult to get from other signals used in biometrics: (1) it requires contact and liveliness for acquisition (2) it changes under stress, rendering it potentially useless if acquired under threatening. Our main objective is to present an innovative and robust solution to the above-mentioned problem. To successfully conduct this goal, we rely on information-theoretic data models for data compression and on similarity metrics related to the approximation of the Kolmogorov complexity. The proposed measure allows the comparison of two (or more) ECG segments, without having to follow traditional approaches that require heartbeat segmentation (described as highly influenced by external or internal interferences). As a first approach, the method was able to cluster the data in three groups: identical record, same participant, different participant, by the stratification of the proposed measure with values near 0 for the same participant and closer to 1 for different participants. A leave-one-out strategy was implemented in order to identify the participant in the database based on his/her ECG. A 1NN classifier was implemented, using as distance measure the method proposed in this work. The classifier was able to identify correctly almost all participants, with an accuracy of 99% in the database used. PMID:26737619

  20. 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.

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

    DOE PAGESBeta

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

    2015-05-14

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

  2. 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.

  3. 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.

  4. Surrogate Motherhood: A Trust-Based Approach.

    PubMed

    Beier, Katharina

    2015-12-01

    Because it is often argued that surrogacy should not be treated as contractual, the question arises in which terms this practice might then be couched. In this article, I argue that a phenomenology of surrogacy centering on the notion of trust provides a description that is illuminating from the moral point of view. My thesis is that surrogacy establishes a complex and extended reproductive unit--the "surrogacy triad" consisting of the surrogate mother, the child, and the intending parents--whose constituents are bound together by mutual trustful commitments. Even though a trust-based approach does not provide an ultimate answer to whether surrogacy should be sanctioned or prohibited, it allows for at least some practical suggestions. In particular, I will argue that, under certain conditions, surrogacy is tenable within familial or other significant relationships, and I will stress the necessity of acknowledging the new relationships and moral commitments that result from this practice. PMID:26449234

  5. Nanotechnology-based approaches in anticancer research

    PubMed Central

    Jabir, Nasimudeen R; Tabrez, Shams; Ashraf, Ghulam Md; Shakil, Shazi; Damanhouri, Ghazi A; Kamal, Mohammad A

    2012-01-01

    Cancer is a highly complex disease to understand, because it entails multiple cellular physiological systems. The most common cancer treatments are restricted to chemotherapy, radiation and surgery. Moreover, the early recognition and treatment of cancer remains a technological bottleneck. There is an urgent need to develop new and innovative technologies that could help to delineate tumor margins, identify residual tumor cells and micrometastases, and determine whether a tumor has been completely removed or not. Nanotechnology has witnessed significant progress in the past few decades, and its effect is widespread nowadays in every field. Nanoparticles can be modified in numerous ways to prolong circulation, enhance drug localization, increase drug efficacy, and potentially decrease chances of multidrug resistance by the use of nanotechnology. Recently, research in the field of cancer nanotechnology has made remarkable advances. The present review summarizes the application of various nanotechnology-based approaches towards the diagnostics and therapeutics of cancer. PMID:22927757

  6. VATS-based approach for robotic lobectomy.

    PubMed

    Melfi, Franca M A; Fanucchi, Olivia; Davini, Federico; Mussi, Alfredo

    2014-05-01

    Lobectomy with systematic lymph node sampling or dissection remains the mainstay of treatment of early stage non-small cell lung cancer. The use of video-assisted thoracic surgery (VATS) to perform lobectomy was first reported in 1992. Advantages of VATS include less trauma and pain, shorter chest drainage duration, decreased hospital stay, and preservation of short-term pulmonary function. However, VATS is characterized by loss of binocular vision and a limited maneuverability of thoracoscopic instruments, an unstable camera platform, and poor ergonomics for the surgeon. To overcome these limitations, robotic systems were developed during the last decades. This article reviews the technical aspects of robotic lobectomy using a VATS-based approach. PMID:24780417

  7. Sepsis management: An evidence-based approach.

    PubMed

    Baig, Muhammad Akbar; Shahzad, Hira; Jamil, Bushra; Hussain, Erfan

    2016-03-01

    The Surviving Sepsis Campaign (SSC) guidelines have outlined an early goal directed therapy (EGDT) which demonstrates a standardized approach to ensure prompt and effective management of sepsis. Having said that, there are barriers associated with the application of evidence-based practice, which often lead to an overall poorer adherence to guidelines. Considering the global burden of disease, data from low- to middle-income countries is scarce. Asia is the largest continent but most Asian countries do not have a well-developed healthcare system and compliance rates to resuscitation and management bundles are as low as 7.6% and 3.5%, respectively. Intensive care units are not adequately equipped and financial concerns limit implementation of expensive treatment strategies. Healthcare policy-makers should be notified in order to alleviate financial restrictions and ensure delivery of standard care to septic patients. PMID:26968289

  8. Strategic approaches to planetary base development

    NASA Technical Reports Server (NTRS)

    Roberts, Barney B.

    1992-01-01

    The evolutionary development of a planetary expansionary outpost is considered in the light of both technical and economic issues. The outline of a partnering taxonomy is set forth which encompasses both institutional and temporal issues related to establishing shared interests and investments. The purely technical issues are discussed in terms of the program components which include nonaerospace technologies such as construction engineering. Five models are proposed in which partnership and autonomy for participants are approached in different ways including: (1) the standard customer/provider relationship; (2) a service-provider scenario; (3) the joint venture; (4) a technology joint-development model; and (5) a redundancy model for reduced costs. Based on the assumed characteristics of planetary surface systems the cooperative private/public models are championed with coordinated design by NASA to facilitate outside cooperation.

  9. Systems Biological Approach of Molecular Descriptors Connectivity: Optimal Descriptors for Oral Bioavailability Prediction

    PubMed Central

    Ahmed, Shiek S. S. J.; Ramakrishnan, V.

    2012-01-01

    Background Poor oral bioavailability is an important parameter accounting for the failure of the drug candidates. Approximately, 50% of developing drugs fail because of unfavorable oral bioavailability. In silico prediction of oral bioavailability (%F) based on physiochemical properties are highly needed. Although many computational models have been developed to predict oral bioavailability, their accuracy remains low with a significant number of false positives. In this study, we present an oral bioavailability model based on systems biological approach, using a machine learning algorithm coupled with an optimal discriminative set of physiochemical properties. Results The models were developed based on computationally derived 247 physicochemical descriptors from 2279 molecules, among which 969, 605 and 705 molecules were corresponds to oral bioavailability, intestinal absorption (HIA) and caco-2 permeability data set, respectively. The partial least squares discriminate analysis showed 49 descriptors of HIA and 50 descriptors of caco-2 are the major contributing descriptors in classifying into groups. Of these descriptors, 47 descriptors were commonly associated to HIA and caco-2, which suggests to play a vital role in classifying oral bioavailability. To determine the best machine learning algorithm, 21 classifiers were compared using a bioavailability data set of 969 molecules with 47 descriptors. Each molecule in the data set was represented by a set of 47 physiochemical properties with the functional relevance labeled as (+bioavailability/−bioavailability) to indicate good-bioavailability/poor-bioavailability molecules. The best-performing algorithm was the logistic algorithm. The correlation based feature selection (CFS) algorithm was implemented, which confirms that these 47 descriptors are the fundamental descriptors for oral bioavailability prediction. Conclusion The logistic algorithm with 47 selected descriptors correctly predicted the oral

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

    PubMed Central

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-01-01

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

  11. Microscopic Description of Few-Body Systems in the Fermionic Molecular Dynamics Approach

    NASA Astrophysics Data System (ADS)

    Neff, T.; Feldmeier, H.

    2009-05-01

    Fermionic Molecular Dynamics (FMD) is a microscopic approach for the description of light nuclei in the p- and sd-shell. Many-body basis states are Slater determinants of Gaussian wave-packets localized in phase space. Brink-type cluster states and harmonic oscillator shell model states are contained as special limiting cases in FMD. The FMD approach is used to study the spectrum of 12C with special emphasis on states with pronounced α-clustering including the Hoyle state. The FMD approach is also used to study 17Ne which is a candidate for a two-proton halo nucleus.

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

    PubMed

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

    2010-08-24

    We report on the quantitative characterization of the plasmonic optical near-field of a single silver nanoparticle. Our approach relies on nanoscale molecular molding of the confined electromagnetic field by photoactivated molecules. We were able to directly image the dipolar profile of the near-field distribution with a resolution better than 10 nm and to quantify the near-field depth and its enhancement factor. A single nanoparticle spectral signature was also assessed. This quantitative characterization constitutes a prerequisite for developing nanophotonic applications. PMID:20687536

  13. Epidermal growth factor receptor and glioblastoma multiforme: molecular basis for a new approach.

    PubMed

    Belda-Iniesta, Cristóbal; de Castro Carpeño, Javier; Sereno, María; González-Barón, Manuel; Perona, Rosario

    2008-02-01

    High-grade gliomas are the most common primary malignant brain tumours. Surgery, radiotherapy and chemotherapy are the cornerstone of actual treatment. In spite of large therapeutic efforts, overall survival is still poor. New molecular data allow a new molecular classification for high-grade gliomas and open a therapeutic window for targeted therapy. Molecular diagnostic tools may provide a basis for receptor-based therapies and enough information to personalise future treatments. In this regard, epidermal growth factor receptor (EGFR) is a target that will play a critical role in the management of glioma patients. This review summarises basic and preclinical data that support future use of therapies against EGFR. PMID:18258505

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

    PubMed

    Okulewicz, Anna; Perec, Agnieszka

    2004-01-01

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

  15. 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.

  16. 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

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

    PubMed

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

    2015-01-01

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

  18. 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

  19. Formal relations connecting different approaches to calculate relativistic effects on molecular magnetic properties

    NASA Astrophysics Data System (ADS)

    Zaccari, D. G.; Ruiz de Azúa, M. C.; Melo, J. I.; Giribet, C. G.

    2006-02-01

    In the present work a set of formal relations connecting different approaches to calculate relativistic effects on magnetic molecular properties are proven. The linear response (LR) within the elimination of the small component (ESC), Breit Pauli, and minimal-coupling approaches are compared. To this end, the leading order ESC reduction of operators within the minimal-coupling four-component approach is carried out. The equivalence of all three approaches within the ESC approximation is proven. It is numerically verified for the NMR nuclear-magnetic shielding tensor taking HX and CH3X (X =Br,I) as model compounds. Formal relations proving the gauge origin invariance of the full relativistic effect on the NMR nuclear-magnetic shielding tensor within the LR-ESC approach are presented.

  20. Adamantane based molecular glass resist for 193 nm lithography

    NASA Astrophysics Data System (ADS)

    Tanaka, Shinji; Ober, Christopher K.

    2006-03-01

    As the feature dimensions decreases there are several issues must be addressed to implement the corresponding technology in high volume production. Line width roughness (LWR) and line edge roughness (LER) are the most important technological issue arises as the feature dimension decreases. In order to improve both of LWR and LER, we have developed novel low molecular weight glass resists as high performance resist materials. These molecular glass resists are adamantane derivatives and are highly transparent at 193 nm. We have prepared series of new molecular glass resists based on adamantane core carrying acetal and ester protecting groups. Particularly, adamantane core derivatives of tripod structure were investigated in detail. Several compositions of them showed glass transition temperatures (Tg) above 120 °C. Lithographic evaluation confirmed their high sensitivity at 254 nm and e-beam exposure. It also resolved feature size as small as 200 nm line/space when it evaluated using e-beam lithography. These new molecular glass resists also have high plasma-etch resistance.

  1. 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

  2. A hybrid approach to simulation of electron transfer in complex molecular systems.

    PubMed

    Kubař, Tomáš; Elstner, Marcus

    2013-10-01

    Electron transfer (ET) reactions in biomolecular systems represent an important class of processes at the interface of physics, chemistry and biology. The theoretical description of these reactions constitutes a huge challenge because extensive systems require a quantum-mechanical treatment and a broad range of time scales are involved. Thus, only small model systems may be investigated with the modern density functional theory techniques combined with non-adiabatic dynamics algorithms. On the other hand, model calculations based on Marcus's seminal theory describe the ET involving several assumptions that may not always be met. We review a multi-scale method that combines a non-adiabatic propagation scheme and a linear scaling quantum-chemical method with a molecular mechanics force field in such a way that an unbiased description of the dynamics of excess electron is achieved and the number of degrees of freedom is reduced effectively at the same time. ET reactions taking nanoseconds in systems with hundreds of quantum atoms can be simulated, bridging the gap between non-adiabatic ab initio simulations and model approaches such as the Marcus theory. A major recent application is hole transfer in DNA, which represents an archetypal ET reaction in a polarizable medium. Ongoing work focuses on hole transfer in proteins, peptides and organic semi-conductors. PMID:23883952

  3. Innovative molecular approach to the identification of Colossoma macropomum and its hybrids.

    PubMed

    Gomes, Fátima; Schneider, Horacio; Barros, Claudene; Sampaio, Dioniso; Hashimoto, Diogo; Porto-Foresti, Fábio; Sampaio, Iracilda

    2012-06-01

    Tambaqui (Colossoma macropomum) is the fish species most commonly raised in the Brazilian fish farms. The species is highly adaptable to captive conditions, and is both fast-growing and relatively fecund. In recent years, artificial breeding has produced hybrids with Characiform species, known as "Tambacu" and "Tambatinga". Identifying hybrids is a difficult process, given their morphological similarities with the parent species. This study presents an innovative molecular approach to the identification of hybrids based primarily on Multiplex PCR of a nuclear gene (α-Tropomyosin), which was tested on 93 specimens obtained from fish farms in northern Brazil. The sequencing of a 505-bp fragment of the Control Region (CR) permitted the identification of the maternal lineage of the specimen, all of which corresponded to C. macropomum. Unexpectedly, only two CR haplotype were found in 93 samples, a very low genetic diversity for the pisciculture of Tambaqui. Multiplex PCR identified 42 hybrids, in contrast with 23 identified by the supplier on the basis of external morphology. This innovative tool has considerable potential for the development of the Brazilian aquaculture, given the possibility of the systematic identification of the genetic traits of both fry-producing stocks, and the fry and juveniles raised in farms. PMID:22534749

  4. Visceral Leishmaniasis: Advancements in Vaccine Development via Classical and Molecular Approaches

    PubMed Central

    Joshi, Sumit; Rawat, Keerti; Yadav, Narendra Kumar; Kumar, Vikash; Siddiqi, Mohammad Imran; Dube, Anuradha

    2014-01-01

    Visceral leishmaniasis (VL) or kala-azar, a vector-borne protozoan disease, shows endemicity in larger areas of the tropical, subtropical and the Mediterranean countries. WHO report suggested that an annual incidence of VL is nearly 200,000 to 400,000 cases, resulting in 20,000 to 30,000 deaths per year. Treatment with available anti-leishmanial drugs are not cost effective, with varied efficacies and higher relapse rate, which poses a major challenge to current kala-azar control program in Indian subcontinent. Therefore, a vaccine against VL is imperative and knowing the fact that recovered individuals developed lifelong immunity against re-infection, it is feasible. Vaccine development program, though time taking, has recently gained momentum with the emergence of omic era, i.e., from genomics to immunomics. Classical as well as molecular methodologies have been overtaken with alternative strategies wherein proteomics based knowledge combined with computational techniques (immunoinformatics) speed up the identification and detailed characterization of new antigens for potential vaccine candidates. This may eventually help in the designing of polyvalent synthetic and recombinant chimeric vaccines as an effective intervention measures to control the disease in endemic areas. This review focuses on such newer approaches being utilized for vaccine development against VL. PMID:25202307

  5. Species identification in cell culture: a two-pronged molecular approach.

    PubMed

    Cooper, Jason K; Sykes, Greg; King, Steve; Cottrill, Karin; Ivanova, Natalia V; Hanner, Robert; Ikonomi, Pranvera

    2007-01-01

    Species identification of cell lines and detection of cross-contamination are crucial for scientific research accuracy and reproducibility. Whereas short tandem repeat profiling offers a solution for a limited number of species, primarily human and mouse, the standard method for species identification of cell lines is enzyme polymorphism. Isoezymology, however, has its own drawbacks; it is cumbersome and the data interpretation is often difficult. Furthermore, the detection sensitivity for cross-contamination is low; it requires large amounts of the contaminant present and cross-contamination within closely related species may go undetected. In this paper, we describe a two-pronged molecular approach that addresses these issues by targeting the mitochondrial genome. First, we developed a multiplex PCR-based assay to rapidly identify the most common cell culture species and quickly detect cross-contaminations among these species. Second, for speciation and identification of a wider variety of cell lines, we amplified and sequenced a 648-bp region, often described as the "barcode region" by using a universal primer mix targeted at conserved sequences of the cytochrome C oxidase I gene (COI). This method was challenged with a panel of 67 cell lines from 45 diverse species. Implementation of these assays will accurately determine the species of cell lines and will reduce the problems of misidentification and cross-contamination that plague research efforts. PMID:17934781

  6. Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach

    PubMed Central

    Lasker, Keren; Förster, Friedrich; Bohn, Stefan; Walzthoeni, Thomas; Villa, Elizabeth; Unverdorben, Pia; Beck, Florian; Aebersold, Ruedi; Sali, Andrej; Baumeister, Wolfgang

    2012-01-01

    The 26S proteasome is at the executive end of the ubiquitin-proteasome pathway for the controlled degradation of intracellular proteins. While the structure of its 20S core particle (CP) has been determined by X-ray crystallography, the structure of the 19S regulatory particle (RP), which recruits substrates, unfolds them, and translocates them to the CP for degradation, has remained elusive. Here, we describe the molecular architecture of the 26S holocomplex determined by an integrative approach based on data from cryoelectron microscopy, X-ray crystallography, residue-specific chemical cross-linking, and several proteomics techniques. The “lid” of the RP (consisting of Rpn3/5/6/7/8/9/11/12) is organized in a modular fashion. Rpn3/5/6/7/9/12 form a horseshoe-shaped heterohexamer, which connects to the CP and roofs the AAA-ATPase module, positioning the Rpn8/Rpn11 heterodimer close to its mouth. Rpn2 is rigid, supporting the lid, while Rpn1 is conformationally variable, positioned at the periphery of the ATPase ring. The ubiquitin receptors Rpn10 and Rpn13 are located in the distal part of the RP, indicating that they were recruited to the complex late in its evolution. The modular structure of the 26S proteasome provides insights into the sequence of events prior to the degradation of ubiquitylated substrates. PMID:22307589

  7. A hybrid approach to simulation of electron transfer in complex molecular systems

    PubMed Central

    Kubař, Tomáš; Elstner, Marcus

    2013-01-01

    Electron transfer (ET) reactions in biomolecular systems represent an important class of processes at the interface of physics, chemistry and biology. The theoretical description of these reactions constitutes a huge challenge because extensive systems require a quantum-mechanical treatment and a broad range of time scales are involved. Thus, only small model systems may be investigated with the modern density functional theory techniques combined with non-adiabatic dynamics algorithms. On the other hand, model calculations based on Marcus's seminal theory describe the ET involving several assumptions that may not always be met. We review a multi-scale method that combines a non-adiabatic propagation scheme and a linear scaling quantum-chemical method with a molecular mechanics force field in such a way that an unbiased description of the dynamics of excess electron is achieved and the number of degrees of freedom is reduced effectively at the same time. ET reactions taking nanoseconds in systems with hundreds of quantum atoms can be simulated, bridging the gap between non-adiabatic ab initio simulations and model approaches such as the Marcus theory. A major recent application is hole transfer in DNA, which represents an archetypal ET reaction in a polarizable medium. Ongoing work focuses on hole transfer in proteins, peptides and organic semi-conductors. PMID:23883952

  8. Chemical stress sensitive luminescent human cells: Molecular biology approach using inducible Drosophila melanogaster hsp22 promoter

    SciTech Connect

    Mandon, C.A.; Diaz, C.; Arrigo, A.-P.; Blum, L.J. . E-mail: Loic.Blum@univ-lyon1.fr

    2005-09-23

    A whole-cell bioassay has been developed for the total toxicity testing of liquid samples. The method is based on the induction of the bioluminescent activity of genetically manipulated mammalian cells. For that purpose, transfection was used to introduce, in HeLa cells, a DNA sensing element that responds to chemical stress agents (heavy metals, genotoxic agents, and endocrine-disrupting chemicals). Such element was designed to direct the expression of a reporting gene (firefly luciferase) through the activation of Drosophila melanogaster hsp22 promoter. A molecular approach was conducted to optimize hsp22 promoter element in order to decrease the background expression level of the reporting gene and to increase the sensitivity of the bioassay for testing endocrine disruptors. As a result, in the presence of 20-100 {mu}M cadmium chloride, a 6-fold increase in luciferase expression was obtained using a specially designed truncated hsp22 promoter construction. The following chemicals known to be found in the polluted samples were tested: CdCl{sub 2}, Cd(NO{sub 3}){sub 2}, NaAsO{sub 2}, alachlore, fentine acetate, thiram, and maneb. The stressing effect of each of them was sensitively detected by the present bioassay in the 0.05-50 {mu}M concentration range.

  9. 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. PMID:26292557

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

    SciTech Connect

    Richters, Dorothee; Kühne, Thomas D.

    2014-04-07

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

  11. 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.

  12. A new approach to the method of source-sink potentials for molecular conduction

    SciTech Connect

    Pickup, Barry T. E-mail: P.W.Fowler@sheffield.ac.uk; Fowler, Patrick W. E-mail: P.W.Fowler@sheffield.ac.uk; Borg, Martha; Sciriha, Irene

    2015-11-21

    We re-derive the tight-binding source-sink potential (SSP) equations for ballistic conduction through conjugated molecular structures in a form that avoids singularities. This enables derivation of new results for families of molecular devices in terms of eigenvectors and eigenvalues of the adjacency matrix of the molecular graph. In particular, we define the transmission of electrons through individual molecular orbitals (MO) and through MO shells. We make explicit the behaviour of the total current and individual MO and shell currents at molecular eigenvalues. A rich variety of behaviour is found. A SSP device has specific insulation or conduction at an eigenvalue of the molecular graph (a root of the characteristic polynomial) according to the multiplicities of that value in the spectra of four defined device polynomials. Conduction near eigenvalues is dominated by the transmission curves of nearby shells. A shell may be inert or active. An inert shell does not conduct at any energy, not even at its own eigenvalue. Conduction may occur at the eigenvalue of an inert shell, but is then carried entirely by other shells. If a shell is active, it carries all conduction at its own eigenvalue. For bipartite molecular graphs (alternant molecules), orbital conduction properties are governed by a pairing theorem. Inertness of shells for families such as chains and rings is predicted by selection rules based on node counting and degeneracy.

  13. A new approach to the method of source-sink potentials for molecular conduction

    NASA Astrophysics Data System (ADS)

    Pickup, Barry T.; Fowler, Patrick W.; Borg, Martha; Sciriha, Irene

    2015-11-01

    We re-derive the tight-binding source-sink potential (SSP) equations for ballistic conduction through conjugated molecular structures in a form that avoids singularities. This enables derivation of new results for families of molecular devices in terms of eigenvectors and eigenvalues of the adjacency matrix of the molecular graph. In particular, we define the transmission of electrons through individual molecular orbitals (MO) and through MO shells. We make explicit the behaviour of the total current and individual MO and shell currents at molecular eigenvalues. A rich variety of behaviour is found. A SSP device has specific insulation or conduction at an eigenvalue of the molecular graph (a root of the characteristic polynomial) according to the multiplicities of that value in the spectra of four defined device polynomials. Conduction near eigenvalues is dominated by the transmission curves of nearby shells. A shell may be inert or active. An inert shell does not conduct at any energy, not even at its own eigenvalue. Conduction may occur at the eigenvalue of an inert shell, but is then carried entirely by other shells. If a shell is active, it carries all conduction at its own eigenvalue. For bipartite molecular graphs (alternant molecules), orbital conduction properties are governed by a pairing theorem. Inertness of shells for families such as chains and rings is predicted by selection rules based on node counting and degeneracy.

  14. New QSAR prediction models derived from GPCR CB2-antagonistic triaryl bis-sulfone analogues by a combined molecular morphological and pharmacophoric approach.

    PubMed

    Chen, J-Z; Myint, K-Z; Xie, X-Q

    2011-01-01

    In order to build quantitative structure-activity relationship (QSAR) models for virtual screening of novel cannabinoid CB2 ligands and hit ranking selections, a new QSAR algorithm has been developed for the cannabinoid ligands, triaryl bis-sulfones, using a combined molecular morphological and pharmacophoric search approach. Both pharmacophore features and shape complementarity were considered using a number of molecular descriptors, including Surflex-Sim similarity and Unity Query fit, in addition to other molecular properties such as molecular weight, ClogP, molecular volume, molecular area, molecular polar volume, molecular polar surface area and dipole moment. Subsequently, partial least squares regression analyses were carried out to derive QSAR models linking bioactivity and the descriptors mentioned, using a training set of 25 triaryl bis-sulfones. Good prediction capability was confirmed for the best QSAR model by evaluation against a test set of a further 20 triaryl bis-sulfones. The pharmacophore and molecular shape-based QSAR scoring function now established can be used to predict the biological properties of virtual hits or untested compounds obtained from ligand-based virtual screenings. PMID:21714749

  15. Femtosecond molecular dynamics of tautomerization in model base pairs

    NASA Astrophysics Data System (ADS)

    Douhal, A.; Kim, S. K.; Zewail, A. H.

    1995-11-01

    HYDROGEN bonds commonly lend robustness and directionality to molecular recognition processes and supramolecular structures1,2. In particular, the two or three hydrogen bonds in Watson-Crick base pairs bind the double-stranded DNA helix and determine the complementarity of the pairing. Watson and Crick pointed out3, however, that the possible tautomers of base pairs, in which hydrogen atoms become attached to the donor atom of the hydrogen bond, might disturb the genetic code, as the tautomer is capable of pairing with different partners. But the dynamics of hydrogen bonds in general, and of this tautomerization process in particular, are not well understood. Here we report observations of the femtosecond dynamics of tautomerization in model base pairs (7-azaindole dimers) containing two hydrogen bonds. Because of the femtosecond resolution of proton motions, we are able to examine the cooperativity of formation of the tautomer (in which the protons on each base are shifted sequentially to the other base), and to determine the characteristic timescales of the motions in a solvent-free environment. We find that the first step occurs on a timescale of a few hundred femtoseconds, whereas the second step, to form the full tautomer, is much slower, taking place within several picoseconds; the timescales are changed significantly by replacing hydrogen with deuterium. These results establish the molecular basis of the dynamics and the role of quantum tunnelling.

  16. Knowledge-based approach to system integration

    NASA Technical Reports Server (NTRS)

    Blokland, W.; Krishnamurthy, C.; Biegl, C.; Sztipanovits, J.

    1988-01-01

    To solve complex problems one can often use the decomposition principle. However, a problem is seldom decomposable into completely independent subproblems. System integration deals with problem of resolving the interdependencies and the integration of the subsolutions. A natural method of decomposition is the hierarchical one. High-level specifications are broken down into lower level specifications until they can be transformed into solutions relatively easily. By automating the hierarchical decomposition and solution generation an integrated system is obtained in which the declaration of high level specifications is enough to solve the problem. We offer a knowledge-based approach to integrate the development and building of control systems. The process modeling is supported by using graphic editors. The user selects and connects icons that represent subprocesses and might refer to prewritten programs. The graphical editor assists the user in selecting parameters for each subprocess and allows the testing of a specific configuration. Next, from the definitions created by the graphical editor, the actual control program is built. Fault-diagnosis routines are generated automatically as well. Since the user is not required to write program code and knowledge about the process is present in the development system, the user is not required to have expertise in many fields.

  17. Evaluating face trustworthiness: a model based approach

    PubMed Central

    Baron, Sean G.; Oosterhof, Nikolaas N.

    2008-01-01

    Judgments of trustworthiness from faces determine basic approach/avoidance responses and approximate the valence evaluation of faces that runs across multiple person judgments. Here, based on trustworthiness judgments and using a computer model for face representation, we built a model for representing face trustworthiness (study 1). Using this model, we generated novel faces with an increased range of trustworthiness and used these faces as stimuli in a functional Magnetic Resonance Imaging study (study 2). Although participants did not engage in explicit evaluation of the faces, the amygdala response changed as a function of face trustworthiness. An area in the right amygdala showed a negative linear response—as the untrustworthiness of faces increased so did the amygdala response. Areas in the left and right putamen, the latter area extended into the anterior insula, showed a similar negative linear response. The response in the left amygdala was quadratic—strongest for faces on both extremes of the trustworthiness dimension. The medial prefrontal cortex and precuneus also showed a quadratic response, but their response was strongest to faces in the middle range of the trustworthiness dimension. PMID:19015102

  18. Pattern recognition tool based on complex network-based approach

    NASA Astrophysics Data System (ADS)

    Casanova, Dalcimar; Backes, André Ricardo; Martinez Bruno, Odemir

    2013-02-01

    This work proposed a generalization of the method proposed by the authors: 'A complex network-based approach for boundary shape analysis'. Instead of modelling a contour into a graph and use complex networks rules to characterize it, here, we generalize the technique. This way, the work proposes a mathematical tool for characterization signals, curves and set of points. To evaluate the pattern description power of the proposal, an experiment of plat identification based on leaf veins image are conducted. Leaf vein is a taxon characteristic used to plant identification proposes, and one of its characteristics is that these structures are complex, and difficult to be represented as a signal or curves and this way to be analyzed in a classical pattern recognition approach. Here, we model the veins as a set of points and model as graphs. As features, we use the degree and joint degree measurements in a dynamic evolution. The results demonstrates that the technique has a good power of discrimination and can be used for plant identification, as well as other complex pattern recognition tasks.

  19. A Density Functional Approach to Polarizable Models: A Kim-Gordon-Response Density Interaction Potential for Molecular Simulations

    SciTech Connect

    Tabacchi, G; Hutter, J; Mundy, C

    2005-04-07

    A combined linear response--frozen electron density model has been implemented in a molecular dynamics scheme derived from an extended Lagrangian formalism. This approach is based on a partition of the electronic charge distribution into a frozen region described by Kim-Gordon theory, and a response contribution determined by the instaneous ionic configuration of the system. The method is free from empirical pair-potentials and the parameterization protocol involves only calculations on properly chosen subsystems. They apply this method to a series of alkali halides in different physical phases and are able to reproduce experimental structural and thermodynamic properties with an accuracy comparable to Kohn-Sham density functional calculations.

  20. A new approach to calculate charge carrier transport mobility in organic molecular crystals from imaginary time path integral simulations

    SciTech Connect

    Song, Linze; Shi, Qiang

    2015-05-07

    We present a new non-perturbative method to calculate the charge carrier mobility using the imaginary time path integral approach, which is based on the Kubo formula for the conductivity, and a saddle point approximation to perform the analytic continuation. The new method is first tested using a benchmark calculation from the numerical exact hierarchical equations of motion method. Imaginary time path integral Monte Carlo simulations are then performed to explore the temperature dependence of charge carrier delocalization and mobility in organic molecular crystals (OMCs) within the Holstein and Holstein-Peierls models. The effects of nonlocal electron-phonon interaction on mobility in different charge transport regimes are also investigated.

  1. A new approach to calculate charge carrier transport mobility in organic molecular crystals from imaginary time path integral simulations

    NASA Astrophysics Data System (ADS)

    Song, Linze; Shi, Qiang

    2015-05-01

    We present a new non-perturbative method to calculate the charge carrier mobility using the imaginary time path integral approach, which is based on the Kubo formula for the conductivity, and a saddle point approximation to perform the analytic continuation. The new method is first tested using a benchmark calculation from the numerical exact hierarchical equations of motion method. Imaginary time path integral Monte Carlo simulations are then performed to explore the temperature dependence of charge carrier delocalization and mobility in organic molecular crystals (OMCs) within the Holstein and Holstein-Peierls models. The effects of nonlocal electron-phonon interaction on mobility in different charge transport regimes are also investigated.

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

    PubMed

    Ioannidis, J P A

    2007-05-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. 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. PMID:26894985

  5. Concurrency-based approaches to parallel programming

    NASA Technical Reports Server (NTRS)

    Kale, L.V.; Chrisochoides, N.; Kohl, J.; Yelick, K.

    1995-01-01

    The inevitable transition to parallel programming can be facilitated by appropriate tools, including languages and libraries. After describing the needs of applications developers, this paper presents three specific approaches aimed at development of efficient and reusable parallel software for irregular and dynamic-structured problems. A salient feature of all three approaches in their exploitation of concurrency within a processor. Benefits of individual approaches such as these can be leveraged by an interoperability environment which permits modules written using different approaches to co-exist in single applications.

  6. Concurrency-based approaches to parallel programming

    SciTech Connect

    Kale, L.V.; Chrisochoides, N.; Kohl, J.

    1995-07-17

    The inevitable transition to parallel programming can be facilitated by appropriate tools, including languages and libraries. After describing the needs of applications developers, this paper presents three specific approaches aimed at development of efficient and reusable parallel software for irregular and dynamic-structured problems. A salient feature of all three approaches in their exploitation of concurrency within a processor. Benefits of individual approaches such as these can be leveraged by an interoperability environment which permits modules written using different approaches to co-exist in single applications.

  7. Reorganization energy of electron transfer processes in ionic fluids: A molecular Debye-Hueckel approach

    SciTech Connect

    Xiao Tiejun; Song Xueyu

    2013-03-21

    The reorganization energy of electron transfer processes in ionic fluids is studied under the linear response approximation using a molecule Debye-Hueckel theory. Reorganization energies of some model reactants of electron transfer reactions in molten salts are obtained from molecular simulations and a molecule Debye-Hueckel approach. Good agreements between simulation results and the results from our theoretical calculations using the same model Hamiltonian are found. Applications of our theory to electron transfer reactions in room temperature ionic liquids further demonstrate that our theoretical approach presents a reliable and accurate methodology for the estimation of reorganization energies of electron transfer reactions in ionic fluids.

  8. 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.

  9. Prognostics and Health Management for Complex system Based on Fusion of Model-based approach and Data-driven approach

    NASA Astrophysics Data System (ADS)

    Hong-feng, Wang

    Prognostics and Health Management has been becoming an effective technology to increasing efficiency and reducing cost for complex system. As for the two major categories methods, both model-based approaches and datadriven approaches have merits and drawbacks. A kind of fusion approaches that integrate model-based approaches and data-driven approaches is presented in this paper and fusion structure is detailed to make full use of their advantages and overcome their limitations.

  10. Reuse: A knowledge-based approach

    NASA Technical Reports Server (NTRS)

    Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

    1992-01-01

    This paper describes our research in automating the reuse process through the use of application domain models. Application domain models are explicit formal representations of the application knowledge necessary to understand, specify, and generate application programs. Furthermore, they provide a unified repository for the operational structure, rules, policies, and constraints of a specific application area. In our approach, domain models are expressed in terms of a transaction-based meta-modeling language. This paper has described in detail the creation and maintenance of hierarchical structures. These structures are created through a process that includes reverse engineering of data models with supplementary enhancement from application experts. Source code is also reverse engineered but is not a major source of domain model instantiation at this time. In the second phase of the software synthesis process, program specifications are interactively synthesized from an instantiated domain model. These specifications are currently integrated into a manual programming process but will eventually be used to derive executable code with mechanically assisted transformations. This research is performed within the context of programming-in-the-large types of systems. Although our goals are ambitious, we are implementing the synthesis system in an incremental manner through which we can realize tangible results. The client/server architecture is capable of supporting 16 simultaneous X/Motif users and tens of thousands of attributes and classes. Domain models have been partially synthesized from five different application areas. As additional domain models are synthesized and additional knowledge is gathered, we will inevitably add to and modify our representation. However, our current experience indicates that it will scale and expand to meet our modeling needs.

  11. 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

  12. 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. PMID:26598514

  13. Tunneling Nanoelectromechanical Switches Based on Compressible Molecular Thin Films.

    PubMed

    Niroui, Farnaz; Wang, Annie I; Sletten, Ellen M; Song, Yi; Kong, Jing; Yablonovitch, Eli; Swager, Timothy M; Lang, Jeffrey H; Bulović, Vladimir

    2015-08-25

    Abrupt switching behavior and near-zero leakage current of nanoelectromechanical (NEM) switches are advantageous properties through which NEMs can outperform conventional semiconductor electrical switches. To date, however, typical NEMs structures require high actuation voltages and can prematurely fail through permanent adhesion (defined as stiction) of device components. To overcome these challenges, in the present work we propose a NEM switch, termed a "squitch," which is designed to electromechanically modulate the tunneling current through a nanometer-scale gap defined by an organic molecular film sandwiched between two electrodes. When voltage is applied across the electrodes, the generated electrostatic force compresses the sandwiched molecular layer, thereby reducing the tunneling gap and causing an exponential increase in the current through the device. The presence of the molecular layer avoids direct contact of the electrodes during the switching process. Furthermore, as the layer is compressed, the increasing surface adhesion forces are balanced by the elastic restoring force of the deformed molecules which can promote zero net stiction and recoverable switching. Through numerical analysis, we demonstrate the potential of optimizing squitch design to enable large on-off ratios beyond 6 orders of magnitude with operation in the sub-1 V regime and with nanoseconds switching times. Our preliminary experimental results based on metal-molecule-graphene devices suggest the feasibility of the proposed tunneling switching mechanism. With optimization of device design and material engineering, squitches can give rise to a broad range of low-power electronic applications. PMID:26244821

  14. 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

  15. Self-assembly of [3]catenanes and a [4]molecular necklace based on a cryptand/paraquat recognition motif.

    PubMed

    Ye, Yang; Wang, Shu-Ping; Zhu, Bin; Cook, Timothy R; Wu, Jing; Li, Shijun; Stang, Peter J

    2015-06-01

    Hierarchical self-assembly centered on metallacyclic scaffolds greatly facilitates the construction of mechanically interlocked structures. The formation of two [3]catenanes and one [4]molecular necklace is presented by utilizing the orthogonality of coordination-driven self-assembly and crown ether-based cryptand/paraquat derivative complexation. The threaded [3]catenanes and [4]molecular necklace were fabricated by using ten and nine total molecular components, respectively, from four and three unique species in solution, respectively. In all cases single supramolecular ensembles were obtained, attesting to the high degree of structural complexity made possible via self-assembly approaches. PMID:25996900

  16. Novel Approaches for Treating Musculoskeletal Diseases: Molecular Orthopedics and Systems Medicine

    PubMed Central

    Mashayekhi, Kaveh; O’Brien, Margaret; Zugun-Eloae, Florin; Labusca, Luminita

    2013-01-01

    Molecular medicine uses knowledge about cell structure and function for disease, diagnostics, stage characterisation and treatment. The advent of genomic technologies is considerably leading to developments in the field of molecular medicine. The accumulation of detailed information about gene expression, epigenetic variability, protein transcription and functional modulation is contributing to a new era in medicine. Rapid and early diagnostic procedures, molecular characterisation of degenerative and proliferative diseases and personalized therapies are predicted to lead to advancements in health prevention and treatment of disease. Diagnostic tools and therapies based on local and /or general modulation of cellular processes for traumatic or degenerative musculoskeletal conditions are becoming available. A logical consequence of the information derived from extensive data gathering, systems biology and systemic medicine has lead to significant improvements in understanding biological structure and function in a simultaneous bottom top and integrative, holistic manner. The description of disease mechanism at an intimate, subcellular level has a dual benefit. A thorough understanding of the crosstalk involved in molecular pathways both in the normal and the diseased state are expanding scientific knowledge and simultaneously are enabling design cell-targeted and individualized therapies. This paper presents a brief overview of current molecular based treatments available to the orthopedic surgeon and introduces the concept of systemic medicine from the perspective of musculoskeletal pathology. PMID:23798982

  17. Moving towards an integrated approach to molecular detection and identification of Toxoplasma gondii

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development of simple, sensitive and rapid methods for detection and identification of Toxoplasma gondii is important for diagnosis and epidemiological studies of the zoonotic disease toxoplasmosis. In the past two decades, molecular methods based on a variety of markers have been developed, each wi...

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

    NASA Astrophysics Data System (ADS)

    Stojanovic, Milan

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

  19. 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.

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

    NASA Astrophysics Data System (ADS)

    Huang, Tony Jun

    2007-04-01

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

  1. 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

  2. Nanotechnology based approaches in cancer therapeutics

    NASA Astrophysics Data System (ADS)

    Kumer Biswas, Amit; Reazul Islam, Md; Sadek Choudhury, Zahid; Mostafa, Asif; Fahim Kadir, Mohammad

    2014-12-01

    The current decades are marked not by the development of new molecules for the cure of various diseases but rather the development of new delivery methods for optimum treatment outcome. Nanomedicine is perhaps playing the biggest role in this concern. Nanomedicine offers numerous advantages over conventional drug delivery approaches and is particularly the hot topic in anticancer research. Nanoparticles (NPs) have many unique criteria that enable them to be incorporated in anticancer therapy. This topical review aims to look at the properties and various forms of NPs and their use in anticancer treatment, recent development of the process of identifying new delivery approaches as well as progress in clinical trials with these newer approaches. Although the outcome of cancer therapy can be increased using nanomedicine there are still many disadvantages of using this approach. We aim to discuss all these issues in this review.

  3. 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

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

    PubMed

    Henkel, J G

    1991-03-01

    Among the most difficult aspects of medicinal chemistry and biochemistry for the student to master are the three-dimensional (3D) nature of drugs and bio-organic substances and the interaction of these substances with 3D targets. Compounding this problem is the fact that such relationships are very difficult to illustrate in a lecture or discussion format. While skeletal molecular models serve a useful role in the learning process, the techniques of PC-based desktop molecular visualization provide a more powerful and effective alternative to the lecture format. These techniques can be implemented on standard MS-DOS PC hardware using one of the commonly available data projection systems. The approach has found considerable use in several areas, including the generation of computer-based lecture aids, the illustration of the molecular shapes of drugs and biochemical structures, the superposition and comparison of drug substances with common pharmacophores, and the illustration of enzyme-substrate interactions. Another related technique, molecular animation, has proven to be quite successful at illustrating the essentials of enzyme mechanisms in the classroom. The "film clips" resulting from this technique may have use beyond the classroom, and further work in this area is underway. PMID:1708280

  5. Minimally invasive surgery of the anterior skull base: transorbital approaches

    PubMed Central

    Gassner, Holger G.; Schwan, Franziska; Schebesch, Karl-Michael

    2016-01-01

    Minimally invasive approaches are becoming increasingly popular to access the anterior skull base. With interdisciplinary cooperation, in particular endonasal endoscopic approaches have seen an impressive expansion of indications over the past decades. The more recently described transorbital approaches represent minimally invasive alternatives with a differing spectrum of access corridors. The purpose of the present paper is to discuss transorbital approaches to the anterior skull base in the light of the current literature. The transorbital approaches allow excellent exposure of areas that are difficult to reach like the anterior and posterior wall of the frontal sinus; working angles may be more favorable and the paranasal sinus system can be preserved while exposing the skull base. Because of their minimal morbidity and the cosmetically excellent results, the transorbital approaches represent an important addition to established endonasal endoscopic and open approaches to the anterior skull base. Their execution requires an interdisciplinary team approach. PMID:27453759

  6. Pharmacophore modeling, in silico screening, molecular docking and molecular dynamics approaches for potential alpha-delta bungarotoxin-4 inhibitors discovery

    PubMed Central

    Kumar, R. Barani; Suresh, M. Xavier; Priya, B. Shanmuga

    2015-01-01

    Background: The alpha-delta bungartoxin-4 (α-δ-Bgt-4) is a potent neurotoxin produced by highly venomous snake species, Bungarus caeruleus, mainly targeting neuronal acetylcholine receptors (nAchRs) and producing adverse biological malfunctions leading to respiratory paralysis and mortality. Objective: In this study, we predicted the three-dimensional structure of α-δ-Bgt-4 using homology modeling and investigated the conformational changes and the key residues responsible for nAchRs inhibiting activity. Materials and Methods: From the selected plants, which are traditionally used for snake bites, the active compounds are taken and performed molecular interaction studies and also used for modern techniques like pharmacophore modeling and mapping and absorption, distribution, metabolism, elimination and toxicity analysis which may increase the possibility of success. Results: Moreover, 100's of drug-like compounds were retrieved and analyzed through computational virtual screening and allowed for pharmacokinetic profiling, molecular docking and dynamics simulation. Conclusion: Finally the top five drug-like compounds having competing level of inhibition toward α-δ-Bgt-4 toxin were suggested based on their interaction with α-δ-Bgt-4 toxin. PMID:26109766

  7. Molecular interactions of UvrB protein and DNA from Helicobacter pylori: Insight into a molecular modeling approach.

    PubMed

    Bavi, Rohit; Kumar, Raj; Rampogu, Shailima; Son, Minky; Park, Chanin; Baek, Ayoung; Kim, Hyong-Ha; Suh, Jung-Keun; Park, Seok Ju; Lee, Keun Woo

    2016-08-01

    Helicobacter pylori (H. pylori) persevere in the human stomach, an environment in which they encounter many DNA-damaging conditions, including gastric acidity. The pathogenicity of H. pylori is enhanced by its well-developed DNA repair mechanism, thought of as 'machinery,' such as nucleotide excision repair (NER). NER involves multi-enzymatic excinuclease proteins (UvrABC endonuclease), which repair damaged DNA in a sequential manner. UvrB is the central component in prokaryotic NER, essential for damage recognition. Therefore, molecular modeling studies of UvrB protein from H. pylori are carried out with homology modeling and molecular dynamics (MD) simulations. The results reveal that the predicted structure is bound to a DNA hairpin with 3-bp stem, an 11-nucleotide loop, and 3-nt 3' overhang. In addition, a mutation of the Y96A variant indicates reduction in the binding affinity for DNA. Free-energy calculations demonstrate the stability of the complex and help identify key residues in various interactions based on residue decomposition analysis. Stability comparative studies between wild type and mutant protein-DNA complexes indicate that the former is relatively more stable than the mutant form. This predicted model could also be useful in designing new inhibitors for UvrB protein, as well as preventing the pathogenesis of H. pylori. PMID:27315565

  8. Molecular and Chemical Genetic Approaches to Developmental Origins of Aging and Disease in Zebrafish

    PubMed Central

    Sasaki, Tomoyuki; Kishi, Shuji

    2013-01-01

    The incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis (“embryonic senescence”), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins

  9. An approach for isolating high-molecular-weight glutenin subunit genes using monoclonal antibodies.

    PubMed

    Wang, H Q; Zhang, X Y

    2006-02-01

    High-molecular-weight glutenin subunits (HMW-GSs) play an important role in the breadmaking quality of wheat flour. In China, cultivars such as Triticum aestivum 'Xiaoyan No. 6' carrying the 1Bx14 and 1By15 glutenin subunits usually have attributes that result in high-quality bread and noodles. HMW-GS 1Bx14 and 1By15 were isolated by preparative sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and used as an antigen to immunize BALB/c mice. A resulting monoclonal antibody belonging to the IgG1 subclass was shown to bind to all HMW-GSs of Triticum aestivum cultivars, but did not bind to other storage proteins of wheat seeds in a Western blot analysis. After screening a complementary DNA expression library from immature seeds of 'Xiaoyan No. 6' using the monoclonal antibody, the HMW-GS 1By15 gene was isolated and fully sequenced. The deduced amino acid sequence showed an extra stretch of 15 amino acid repeats consisting of a hexapeptide and a nonapeptide in the repetitive domain of this y-type HMW subunit. Bacterial expression of a modified 1By15 gene, in which the coding sequence for the signal peptide was removed and a BamHI site eliminated, gave rise to a protein with mobility identical to that of HMW-GSs extracted from seeds of 'Xiaoyan No. 6' via SDS-PAGE. This approach for isolating genes using specific monoclonal antibody against HMW-GS genes is a good alternative to the extensively used polymerase chain reaction (PCR) technology based on sequence homology of HMW-GSs in wheat and its relatives. PMID:16498468

  10. Single-molecular diodes based on opioid derivatives.

    PubMed

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

    2015-12-01

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

  11. Single-walled carbon nanotube based molecular switch tunnel junctions.

    PubMed

    Diehl, Michael R; Steuerman, David W; Tseng, Hsian-Rong; Vignon, Scott A; Star, Alexander; Celestre, Paul C; Stoddart, J Fraser; Heath, James R

    2003-12-15

    This article describes two-terminal molecular switch tunnel junctions (MSTJs) which incorporate a semiconducting, single-walled carbon nanotube (SWNT) as the bottom electrode. The nanotube interacts noncovalently with a monolayer of bistable, nondegenerate [2]catenane tetracations, self-organized by their supporting amphiphilic dimyristoylphosphatidyl anions which shield the mechanically switchable tetracations from a two-micrometer wide metallic top electrode. The resulting 0.002 micron 2 area tunnel junction addresses a nanometer wide row of approximately 2000 molecules. Active and remnant current-voltage measurements demonstrated that these devices can be reconfigurably switched and repeatedly cycled between high and low current states under ambient conditions. Control compounds, including a degenerate [2]catenane, were explored in support of the mechanical origin of the switching signature. These SWNT-based MSTJs operate like previously reported silicon-based MSTJs, but differently from similar devices incorporating bottom metal electrodes. The relevance of these results with respect to the choice of electrode materials for molecular electronics devices is discussed. PMID:14714382

  12. Free Energy Calculations using a Swarm-Enhanced Sampling Molecular Dynamics Approach

    PubMed Central

    Burusco, Kepa K; Bruce, Neil J; Alibay, Irfan; Bryce, Richard A

    2015-01-01

    Free energy simulations are an established computational tool in modelling chemical change in the condensed phase. However, sampling of kinetically distinct substates remains a challenge to these approaches. As a route to addressing this, we link the methods of thermodynamic integration (TI) and swarm-enhanced sampling molecular dynamics (sesMD), where simulation replicas interact cooperatively to aid transitions over energy barriers. We illustrate the approach by using alchemical alkane transformations in solution, comparing them with the multiple independent trajectory TI (IT-TI) method. Free energy changes for transitions computed by using IT-TI grew increasingly inaccurate as the intramolecular barrier was heightened. By contrast, swarm-enhanced sampling TI (sesTI) calculations showed clear improvements in sampling efficiency, leading to more accurate computed free energy differences, even in the case of the highest barrier height. The sesTI approach, therefore, has potential in addressing chemical change in systems where conformations exist in slow exchange. PMID:26418190

  13. A NEW APPROACH TO UNDERSTANDING THE MOLECULAR MECHANISMS THROUGH WHICH ESTROGENS AFFECT COGNITION

    PubMed Central

    Frick, Karyn M.; Fernandez, Stephanie M.; Harburger, Lauren L.

    2009-01-01

    Traditional approaches to the study of hormones and cognition have been primarily observational or correlational in nature. Because this work does not permit causal relationships to be identified, very little is known about the specific molecules and cellular events through which hormones affect cognitive function. In this review, we propose a new approach to study hormones and memory, where the systematic blocking of cellular events can reveal which such events are necessary for hormones to influence memory consolidation. The discussion will focus on the modulation of the hippocampus and hippocampal memory by estrogens, given the extensive literature on this subject, and will illustrate how the application of this approach is beginning to reveal important new information about the molecular mechanisms through which estrogens modulate memory consolidation. The clinical relevance of this work will also be discussed. PMID:19913600

  14. Intra-molecular Triplet Energy Transfer is a General Approach to Improve Organic Fluorophore Photostability

    PubMed Central

    Zheng, Qinsi; Jockusch, Steffen; Rodríguez-Calero, Gabriel G.; Zhou, Zhou; Zhao, Hong; Altman, Roger B.; Abruña, Héctor D.; Blanchard, Scott C.

    2015-01-01

    Bright, long-lasting and non-phototoxic organic fluorophores are essential to the continued advancement of biological imaging. Traditional approaches towards achieving photostability, such as the removal of molecular oxygen and the use of small-molecule additives in solution, suffer from potentially toxic side effects, particularly in the context of living cells. The direct conjugation of small-molecule triplet state quenchers, such as cyclooctatetraene (COT), to organic fluorophores has the potential to bypass these issues by restoring reactive fluorophore triplet states to the ground state through intra-molecular triplet energy transfer. Such methods have enabled marked improvement in cyanine fluorophore photostability spanning the visible spectrum. However, the generality of this strategy to chemically and structurally diverse fluorophore species has yet to be examined. Here, we show that the proximal linkage of COT increases the photon yield of a diverse range of organic fluorophores widely used in biological imaging applications, demonstrating that the intra-molecular triplet energy transfer mechanism is a potentially general approach for improving organic fluorophore performance and photostability. PMID:26700693

  15. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials

    PubMed Central

    Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O’Neal, Michael

    2015-01-01

    In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes. PMID:26392755

  16. A Molecular Surface Functionalization Approach to Tuning Nanoparticle Electrocatalysts for Carbon Dioxide Reduction.

    PubMed

    Cao, Zhi; Kim, Dohyung; Hong, Dachao; Yu, Yi; Xu, Jun; Lin, Song; Wen, Xiaodong; Nichols, Eva M; Jeong, Keunhong; Reimer, Jeffrey A; Yang, Peidong; Chang, Christopher J

    2016-07-01

    Conversion of the greenhouse gas carbon dioxide (CO2) to value-added products is an important challenge for sustainable energy research, and nanomaterials offer a broad class of heterogeneous catalysts for such transformations. Here we report a molecular surface functionalization approach to tuning gold nanoparticle (Au NP) electrocatalysts for reduction of CO2 to CO. The N-heterocyclic (NHC) carbene-functionalized Au NP catalyst exhibits improved faradaic efficiency (FE = 83%) for reduction of CO2 to CO in water at neutral pH at an overpotential of 0.46 V with a 7.6-fold increase in current density compared to that of the parent Au NP (FE = 53%). Tafel plots of the NHC carbene-functionalized Au NP (72 mV/decade) vs parent Au NP (138 mV/decade) systems further show that the molecular ligand influences mechanistic pathways for CO2 reduction. The results establish molecular surface functionalization as a complementary approach to size, shape, composition, and defect control for nanoparticle catalyst design. PMID:27322487

  17. Molecular approaches to improvement of Jatropha curcas Linn. as a sustainable energy crop.

    PubMed

    Sudhakar Johnson, T; Eswaran, Nalini; Sujatha, M

    2011-09-01

    With the increase in crude oil prices, climate change concerns and limited reserves of fossil fuel, attention has been diverted to alternate renewable energy sources such as biofuel and biomass. Among the potential biofuel crops, Jatropha curcas L, a non-domesticated shrub, has been gaining importance as the most promising oilseed, as it does not compete with the edible oil supplies. Economic relevance of J. curcas for biodiesel production has promoted world-wide prospecting of its germplasm for crop improvement and breeding. However, lack of adequate genetic variation and non-availability of improved varieties limited its prospects of being a successful energy crop. In this review, we present the progress made in molecular breeding approaches with particular reference to tissue culture and genetic transformation, genetic diversity assessment using molecular markers, large-scale transcriptome and proteome studies, identification of candidate genes for trait improvement, whole genome sequencing and the current interest by various public and private sector companies in commercial-scale cultivation, which highlights the revival of Jatropha as a sustainable energy crop. The information generated from molecular markers, transcriptome profiling and whole genome sequencing could accelerate the genetic upgradation of J. curcas through molecular breeding. PMID:21584678

  18. May Diet and Dietary Supplements Improve the Wellness of Multiple Sclerosis Patients? A Molecular Approach

    PubMed Central

    Riccio, Paolo; Rossano, Rocco; Liuzzi, Grazia Maria

    2010-01-01

    Multiple sclerosis is a complex and multifactorial neurological disease, and nutrition is one of the environmental factors possibly involved in its pathogenesis. At present, the role of nutrition is unclear, and MS therapy is not associated to a particular diet. MS clinical trials based on specific diets or dietary supplements are very few and in some cases controversial. To understand how diet can influence the course of MS and improve the wellness of MS patients, it is necessary to identify the dietary molecules, their targets and the molecular mechanisms involved in the control of the disease. The aim of this paper is to provide a molecular basis for the nutritional intervention in MS by evaluating at molecular level the effect of dietary molecules on the inflammatory and autoimmune processes involved in the disease. PMID:21461338

  19. PET-Based Molecular Imaging in Designing Personalized Management Strategy in Gastroenteropancreatic Neuroendocrine Tumors.

    PubMed

    Basu, Sandip; Ranade, Rohit; Ostwal, Vikas; Shrikhande, Shailesh V

    2016-07-01

    In recent years, PET-based molecular functional imaging has been increasingly used in neuroendocrine tumors for tailoring of treatment strategies to the individual characteristics of each patient. For each particular patient, the relative tracer uptake by the dual-tracer PET imaging approach (with 68Ga-DOTANOC/TATE and 18F-FDG) frequently plays an important role along with the histopathologic tumor grades for selecting the optimal treatment approach for advanced/metastatic cases. Various tumor-specific parameters have resulted in development of such precision-medicine type model in this biologically heterogeneous group of tumors. The traditional advantages of PET/computed tomography in terms of disease staging are also applicable for personalization of management. From the medical oncologist's standpoint, multitracer PET-based information and staging is of significant importance (in addition to the histologic grades) in selecting the appropriate chemotherapy regimen and monitoring response on an individual basis in the course of treatment. PMID:27321028

  20. Fluorescence Correlation Spectroscopy Simulations of Photophysical Phenomena and Molecular Interactions: A Molecular Dynamics/Monte Carlo Approach

    PubMed Central

    Dix, James A.; Hom, Erik F. Y.; Verkman, A. S.

    2011-01-01

    Fluorescence correlation spectroscopy (FCS) is being applied increasingly to study diffusion and interactions of fluorescently labeled macromolecules in complex biological systems. Fluctuations in detected fluorescence, δF(t), are expressed as time-correlation functions, G(τ), and photon-count histograms, P(k;ΔT). Here, we developed a generalized simulation approach to compute G(τ) and P(k;ΔT) for complex systems with arbitrary geometry, photophysics, diffusion, and macromolecular interactions. G(τ) and P(k;ΔT) were computed from δF(t) generated by a Brownian dynamics simulation of single-molecule trajectories followed by a Monte Carlo simulation of fluorophore excitation and detection statistics. Simulations were validated by comparing analytical and simulated G(τ) and P(k;ΔT) for diffusion of noninteracting fluorophores in a three-dimensional Gaussian excitation and detection volume. Inclusion of photobleaching and triplet-state relaxation produced significant changes in G(τ) and P(k;ΔT). Simulations of macromolecular interactions and complex diffusion were done, including transient fluorophore binding to an immobile matrix, cross-correlation analysis of interacting fluorophores, and anomalous sub- and superdiffusion. The computational method developed here is generally applicable for simulating FCS measurements on systems complicated by fluorophore interactions or molecular crowding, and experimental protocols for which G(τ) and P(k;ΔT) cannot be computed analytically. PMID:16471761

  1. Antagonistic molecular interactions of photosynthetic pigments with molecular disease targets: a new approach to treat AD and ALS.

    PubMed

    Krishnaraj, R Navanietha; Kumari, S S Sreeja; Mukhopadhyay, Sudit Sekhar

    2016-01-01

    Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are progressive neurodegenerative diseases that affect the neurons in the brain and the spinal cord. Neuroinflamation and apoptosis are key players in the progressive damage of the neurons in AD and ALS. Currently, there is no drug to offer complete cure for both these diseases. Riluzole is the only available drug that can prolong the life time of the ALS patients for nearly 3 months. Molecules that offer good HIT to the molecular targets of ALS will help to treat AD and ALS patients. P53 kinase receptor (4AT3), EphA4 (3CKH) and histone deacetylase (3SFF) are the promising disease targets of AD and ALS. This paper discusses on a new approach to combat neurodegenerative diseases using photosynthetic pigments. The docking studies were performed with the Autodock Vina algorithm to predict the binding of the natural pigments such as β carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin on these targets. The β carotene, phycoerythrin and phycocyanin had higher binding energies indicating the antagonistic activity to the disease targets. These pigments serve as a potential therapeutic molecule to treat neuroinflammation and apoptosis in the AD and ALS patients. PMID:26053508

  2. Thermal transport in porous Si nanowires from approach-to-equilibrium molecular dynamics calculations

    NASA Astrophysics Data System (ADS)

    Cartoixà, Xavier; Dettori, Riccardo; Melis, Claudio; Colombo, Luciano; Rurali, Riccardo

    2016-07-01

    We study thermal transport in porous Si nanowires (SiNWs) by means of approach-to-equilibrium molecular dynamics simulations. We show that the presence of pores greatly reduces the thermal conductivity, κ, of the SiNWs as long mean free path phonons are suppressed. We address explicitly the dependence of κ on different features of the pore topology—such as the porosity and the pore diameter—and on the nanowire (NW) geometry—diameter and length. We use the results of the molecular dynamics calculations to tune an effective model, which is capable of capturing the dependence of κ on porosity and NW diameter. The model illustrates the failure of Matthiessen's rule to describe the coupling between boundary and pore scattering, which we account for by the inclusion of an additional empirical term.

  3. Control of molecular rotor rotational frequencies in porous coordination polymers using a solid-solution approach.

    PubMed

    Inukai, Munehiro; Fukushima, Tomohiro; Hijikata, Yuh; Ogiwara, Naoki; Horike, Satoshi; Kitagawa, Susumu

    2015-09-30

    Rational design to control the dynamics of molecular rotors in crystalline solids is of interest because it offers advanced materials with precisely tuned functionality. Herein, we describe the control of the rotational frequency of rotors in flexible porous coordination polymers (PCPs) using a solid-solution approach. Solid-solutions of the flexible PCPs [{Zn(5-nitroisophthalate)x(5-methoxyisophthalate)1-x(deuterated 4,4'-bipyridyl)}(DMF·MeOH)]n allow continuous modulation of cell volume by changing the solid-solution ratio x. Variation of the isostructures provides continuous changes in the local environment around the molecular rotors (pyridyl rings of the 4,4'-bipyridyl group), leading to the control of the rotational frequency without the need to vary the temperature. PMID:26368067

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

    PubMed

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

    2016-06-01

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

  5. Molecular targets of TBBPA in zebrafish analysed through integration of genomic and proteomic approaches.

    PubMed

    De Wit, Marijke; Keil, Dorien; Remmerie, Noor; van der Ven, Karlijn; van den Brandhof, Evert-Jan; Knapen, Dries; Witters, Erwin; De Coen, Wim

    2008-12-01

    Tetrabromobisphenol-A (TBBPA) is nowadays one of the most frequently used brominated flame retardants (BFRs) and can be considered as a high production volume chemical. Over the last decade, numerous reports of increasing concentrations of BFRs in the environment and humans have been published. However, the toxicological knowledge on TBBPA, and more specifically its molecular mode of action, is rather fragmentary. In this study two populations of adult zebrafish (Danio rerio) were exposed for 14 days to 0.75 microM and 1.5 microM TBBPA. Subsequently, we employed a combined transcriptomic and proteomic approach to evaluate the molecular effects of TBBPA in zebrafish liver. Oligonucleotide microarrays were used to study the effects on gene expression levels. These results were validated through real-time PCR. The proteome of the liver was analysed by means of differential in-gel electrophoresis (DiGE), an innovative application of traditional 2D-PAGE. Combination of the extracted datasets allowed reassembling of individual molecular responses into a comprehensive overview of affected molecular pathways. Interpretation of the results depicted an interference of thyroid and Vitamin A homeostasis in the exposed zebrafish, TBBPA also elicited responses indicating onset of oxidative stress and general stress responses. Additionally, numerous differentially expressed transcripts could be associated with defence mechanisms or corresponded to metabolizing enzymes. Furthermore, cellular metabolism was clearly affected, illustrated as disturbance of e.g. lipid, carbohydrate, and organic acid metabolic processes. Summarizing, these results enabled us to hypothesize several working mechanisms of TBBPA and demonstrated the potential of a combined genome and proteome approach to generate detailed mechanistic toxicological information. PMID:18976794

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

    PubMed

    Miyawaki, Atsushi; Niino, Yusuke

    2015-05-21

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

  7. Molecular dating of the diversification of Phyllostominae bats based on nuclear and mitochondrial DNA sequences.

    PubMed

    Hoffmann, Federico G; Hoofer, Steven R; Baker, Robert J

    2008-11-01

    Times of divergence among the three tribes included within the subfamily Phyllostominae were estimated using a Bayesian approach to infer dates of divergence based on mitochondrial and nuclear sequence data. The subfamily Phyllostominae is particularly attractive for such analysis, as it is one of the few groups of bats to have fossil specimens. Our molecular time analyses suggest that diversification among tribes and genera of phyllostomine bats occurred during the Early to Mid-Miocene, and was coincident with diversification events in two co distributed taxa: Caviomorph rodents and New World monkeys. PMID:18727956

  8. Graphene-based nanomaterials as molecular imaging agents.

    PubMed

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

    2015-01-01

    Molecular imaging (MI) is a noninvasive, real-time visualization of biochemical events at the cellular and molecular level within tissues, living cells, and/or intact objects that can be advantageously applied in the areas of diagnostics, therapeutics, drug discovery, and development in understanding the nanoscale reactions including enzymatic conversions and protein-protein interactions. Consequently, over the years, great advancement has been made in the development of a variety of MI agents such as peptides, aptamers, antibodies, and various nanomaterials (NMs) including single-walled carbon nanotubes. Recently, graphene, a material popularized by Geim & Novoselov, has ignited considerable research efforts to rationally design and execute a wide range of graphene-based NMs making them an attractive platform for developing highly sensitive MI agents. Owing to their exceptional physicochemical and biological properties combined with desirable surface engineering, graphene-based NMs offer stable and tunable visible emission, small hydrodynamic size, low toxicity, and high biocompatibility and thus have been explored for in vitro and in vivo imaging applications as a promising alternative of traditional imaging agents. This review begins by describing the intrinsic properties of graphene and the key MI modalities. After which, we provide an overview on the recent advances in the design and development as well as physicochemical properties of the different classes of graphene-based NMs (graphene-dye conjugates, graphene-antibody conjugates, graphene-nanoparticle composites, and graphene quantum dots) being used as MI agents for potential applications including theranostics. Finally, the major challenges and future directions in the field will be discussed. PMID:25857851

  9. Modifying the photoelectric behavior of bacteriorhodopsin by site-directed mutagenesis: electrochemical and genetic engineering approaches to molecular devices

    NASA Astrophysics Data System (ADS)

    Hong, F. T.; Hong, F. H.; Needleman, R. B.; Ni, B.; Chang, M.

    1992-07-01

    Bacteriorhodopsins (bR's) modified by substitution of the chromophore with synthetic vitamin A analogues or by spontaneous mutation have been reported as successful examples of using biomaterials to construct molecular optoelectronic devices. The operation of these devices depends on desirable optical properties derived from molecular engineering. This report examines the effect of site-directed mutagenesis on the photoelectric behavior of bR thin films with an emphasis on their application to the construction of molecular devices based on their unique photoelectric behavior. We examine the photoelectric signals induced by a microsecond light pulse in thin films which contain reconstituted oriented purple membrane sheets isolated from several mutant strains of Halobacterium halobium. A recently developed expression system is used to synthesize mutant bR's in their natural host, H. halobium. We then use a unique analytical method (tunable voltage clamp method) to investigate the effect of pH on the relaxation of two components of the photoelectric signals, B1 and B2. We found that for the four mutant bR's examined, the pH dependence of the B2 component varies significantly. Our results suggest that genetic engineering approaches can produce mutant bR's with altered photoelectric characteristics that can be exploited in the construction of devices.

  10. Determining Diversity of Freshwater Fungi on Decaying Leaves: Comparison of Traditional and Molecular Approaches

    PubMed Central

    Nikolcheva, Liliya G.; Cockshutt, Amanda M.; Bärlocher, Felix

    2003-01-01

    Traditional microscope-based estimates of species richness of aquatic hyphomycetes depend upon the ability of the species in the community to sporulate. Molecular techniques which detect DNA from all stages of the life cycle could potentially circumvent the problems associated with traditional methods. Leaf disks from red maple, alder, linden, beech, and oak as well as birch wood sticks were submerged in a stream in southeastern Canada for 7, 14, and 28 days. Fungal biomass, estimated by the amount of ergosterol present, increased with time on all substrates. Alder, linden, and maple leaves were colonized earlier and accumulated the highest fungal biomass. Counts and identifications of released conidia suggested that fungal species richness increased, while community evenness decreased, with time (up to 11 species on day 28). Conidia of Articulospora tetracladia dominated. Modifications of two molecular methods—denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism (T-RFLP) analysis—suggested that both species richness and community evenness decreased with time. The dominant ribotype matched that of A. tetracladia. Species richness estimates based on DGGE were consistently higher than those based on T-RFLP analysis and exceeded those based on spore identification on days 7 and 14. Since traditional and molecular techniques assess different aspects of the fungal organism, both are essential for a balanced view of fungal succession on leaves decaying in streams. PMID:12732520

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

    Energy Science and Technology Software Center (ESTSC)

    1995-03-01

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

  12. A molecularly based theory for electron transfer reorganization energy

    NASA Astrophysics Data System (ADS)

    Zhuang, Bilin; Wang, Zhen-Gang

    2015-12-01

    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.

  13. 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.

  14. Acceleration of Semiempirical Quantum Mechanical Calculations by Extended Lagrangian Molecular Dynamics Approach.

    PubMed

    Nam, Kwangho

    2013-08-13

    The implementation and performance of the atom-centered density matrix propagation (ADMP) [J. Chem. Phys. 2001, 114, 9758] and the curvy-steps (CURV) methods [J. Chem. Phys. 2004, 121, 1152] are described. These methods solve the electronic Schrödinger equation approximately by propagating the electronic degrees of freedom using the extended Lagrangian molecular dynamics (ELMD) simulation approach. The ADMP and CURV methods are implemented and parallelized to accelerate semiempirical quantum mechanical (QM) methods (such as the MNDO, AM1, PM3, MNDO/d, and AM1/d methods). Test calculations show that both the ADMP and the CURV methods are 2∼4 times faster than the Born-Oppenheimer molecular dynamics (BOMD) method and conserve the total energy well. The accuracy of the ADMP and CURV simulations is comparable to the BOMD simulations. The parallel implementation accelerates the MD simulation by up to 28 fold for the ADMP method and 25 fold for the CURV method, respectively, relative to the speed of the single core BOMD. In addition, a multiple time scale (MTS) approach is introduced to further speed up the semiempirical QM and QM/MM ELMD simulations. Since a larger integration time step is used for the propagation of the nuclear coordinates than that for the electronic degrees of freedom, the MTS approach allows the ELMD simulation to be carried out with a time step that is larger than the time step accessible by the original ADMP and CURV methods. It renders MD simulation to be carried out about 20 times faster than the BOMD simulation, and yields results that are comparable to the single time scale simulation results. The use of the methods introduced in the present work provides an efficient way to extend the length of the QM and QM/MM molecular dynamics simulations beyond the length accessible by BOMD simulation. PMID:26584095

  15. Assessment of Person Fit Using Resampling-Based Approaches

    ERIC Educational Resources Information Center

    Sinharay, Sandip

    2016-01-01

    De la Torre and Deng suggested a resampling-based approach for person-fit assessment (PFA). The approach involves the use of the [math equation unavailable] statistic, a corrected expected a posteriori estimate of the examinee ability, and the Monte Carlo (MC) resampling method. The Type I error rate of the approach was closer to the nominal level…

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

    PubMed

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

    2016-05-15

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

  17. Monte Carlo approach to the spatial deposition of energy by electrons in molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Heaps, M. G.; Green, A. E. S.

    1974-01-01

    The Monte Carlo (MC) and continuous slowdown approximation (CSDA) approaches to the spatial deposition of energy by electrons are compared using the same detailed atomic cross section (DACS). It is found that the CSDA method overestimates the amount of energy that is deposited near the end of the path for electrons above a few hundred electron volts. The MC results are in approximate agreement with experimental data in such a way as to be relatively independent of the actual gas used. Our MC results are extended to obtain the three-dimensional deposition of energy by sub-keV electrons in molecular hydrogen.

  18. Rotational Profiles of Molecular Absorption Bands in Astrophysically Relevant Conditions: Ab-Initio Approach

    SciTech Connect

    Malloci, Giuliano; Mulas, Giacomo; Cappellini, Giancarlo; Satta, Guido; Porceddu, Ignazio; Benvenuti, Piero

    2004-05-01

    A theoretical study of rotational profiles of molecular absorption bands is essential for direct comparison with observations of diffuse interstellar bands. Applications using gaussian quantum-chemical approach within DFT are presented. Structural and vibrational properties of the polycyclic aromatic hydrocarbon ovalene cation (C32H14+) are obtained. We discuss the expected profile of the first electronic transition of such molecule, obtained with a Monte Carlo model of its rotation in the physical conditions of low temperatures and absence of collisions which are characteristic of the interstellar medium (ISM).

  19. Evaluating a pivot-based approach for bilingual lexicon extraction.

    PubMed

    Kim, Jae-Hoon; Kwon, Hong-Seok; Seo, Hyeong-Won

    2015-01-01

    A pivot-based approach for bilingual lexicon extraction is based on the similarity of context vectors represented by words in a pivot language like English. In this paper, in order to show validity and usability of the pivot-based approach, we evaluate the approach in company with two different methods for estimating context vectors: one estimates them from two parallel corpora based on word association between source words (resp., target words) and pivot words and the other estimates them from two parallel corpora based on word alignment tools for statistical machine translation. Empirical results on two language pairs (e.g., Korean-Spanish and Korean-French) have shown that the pivot-based approach is very promising for resource-poor languages and this approach observes its validity and usability. Furthermore, for words with low frequency, our method is also well performed. PMID:25983745

  20. Evaluating a Pivot-Based Approach for Bilingual Lexicon Extraction

    PubMed Central

    Kim, Jae-Hoon; Kwon, Hong-Seok; Seo, Hyeong-Won

    2015-01-01

    A pivot-based approach for bilingual lexicon extraction is based on the similarity of context vectors represented by words in a pivot language like English. In this paper, in order to show validity and usability of the pivot-based approach, we evaluate the approach in company with two different methods for estimating context vectors: one estimates them from two parallel corpora based on word association between source words (resp., target words) and pivot words and the other estimates them from two parallel corpora based on word alignment tools for statistical machine translation. Empirical results on two language pairs (e.g., Korean-Spanish and Korean-French) have shown that the pivot-based approach is very promising for resource-poor languages and this approach observes its validity and usability. Furthermore, for words with low frequency, our method is also well performed. PMID:25983745

  1. Biomarker and molecular isotope approaches to deconvolve the terrestrial carbon isotope record: modern and Eocene calibrations

    NASA Astrophysics Data System (ADS)

    Diefendorf, A. F.; Freeman, K. H.; Wing, S.; Currano, E. D.

    2010-12-01

    Climate, biome, and plant community are important predictors of carbon isotope patterns recorded in leaves and leaf waxes. However, signatures recorded by terrestrial organic carbon and lipids that have mixed floral sources (e.g., n-alkanes) potentially reflect both plant community changes and climate. More taxonomically specific proxies for plants (i.e., di- and tri-terpenoids for conifers and angiosperms, respectively), can help to resolve the relative influences of changing community and climate, provided differences in biomarker production and lipid biosynthetic fractionation among plants can be better constrained. We present biomarker abundance and carbon isotope values for lipids from leaves, branches and bark of 44 tree species, representing 21 families including deciduous and evergreen conifers and angiosperms. n-alkane production differs greatly between conifer and angiosperm leaves. Both deciduous and evergreen angiosperms make significantly more n-alkanes than conifers, with n-alkanes not detected in over half of the conifers in our study. Terpenoid abundances scale strongly with leaf habit: evergreen species have significantly higher abundances. We combine these relative differences in lipid production with published estimates of fluxes for leaf litter from conifer and angiosperm trees to develop a new proxy approach for estimating paleo plant community inputs to ancient soils and sediments. To test our modern calibration results, we have evaluated n-alkanes and terpenoids from laterally extensive (~18 km) carbonaceous shales and mudstones in Eocene sediments (52.6 Ma) at Fifteenmile Creek in the Bighorn Basin (WY, USA). Our terpenoid-based proxy predicts on average a 40% conifer community, which is remarkably close in agreement with a fossil-based estimate of 36%. n-alkane carbon isotope fractionation (leaf-lipid) differs among plant types, with conifer n-alkanes about 2-3‰ 13C enriched relative to those in angiosperms. Since conifer leaves are

  2. Development of two molecular approaches for differentiation of clinically relevant yeast species closely related to Candida guilliermondii and Candida famata.

    PubMed

    Feng, Xiaobo; Wu, Jingsong; Ling, Bo; Yang, Xianwei; Liao, Wanqing; Pan, Weihua; Yao, Zhirong

    2014-09-01

    The emerging pathogens Candida palmioleophila, Candida fermentati, and Debaryomyces nepalensis are often misidentified as Candida guilliermondii or Candida famata in the clinical laboratory. Due to the significant differences in antifungal susceptibilities and epidemiologies among these closely related species, a lot of studies have focused on the identification of these emerging yeast species in clinical specimens. Nevertheless, limited tools are currently available for their discrimination. Here, two new molecular approaches were established to distinguish these closely related species. The first approach differentiates these species by use of restriction fragment length polymorphism analysis of partial internal transcribed spacer 2 (ITS2) and large subunit ribosomal DNA with the enzymes BsaHI and XbaI in a double digestion. The second method involves a multiplex PCR based on the intron size differences of RPL18, a gene coding for a protein component of the large (60S) ribosomal subunit, and species-specific amplification. These two methods worked well in differentiation of these closely related yeast species and have the potential to serve as effective molecular tools suitable for laboratory diagnoses and epidemiological studies. PMID:24951804

  3. Two new molecular bases for the Dombrock null phenotype.

    PubMed

    Rios, Maria; Storry, Jill R; Hue-Roye, Kim; Chung, Amy; Reid, Marion E

    2002-06-01

    Red blood cells (RBCs) with the Do(null) phenotype lack all antigens in the Dombrock blood group system, i.e. Do(a), Do(b), Gy(a), Hy and Jo(a). Sequence analysis of DNA from one proband with the Do(null) phenotype revealed a single nucleotide mutation of t to c in the donor splice site of DO (IVS1 + 2t > c), with outsplicing of exon 2. Analysis of a second proband revealed a homozygous nonsense mutation 442 C > T in exon 2 predicting a premature stop codon (Gln148 Stop). The molecular bases described in these two probands provide an explanation for the lack of Do glycoprotein on their RBCs. PMID:12028057

  4. 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.

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

    PubMed

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

    2013-10-01

    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

  6. 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

  7. DNA Aptamer Based Nanodrugs: Molecular Engineering for Efficiency.

    PubMed

    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

    2015-10-01

    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 made in multiple aptamer-based nanodrug systems that have emerged in recent years, including studies in the infant stage of "proof-of-concept". PMID:26177853

  8. 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

  9. Preparation of a novel drug sensor using a molecular imprinted polymer approach

    NASA Astrophysics Data System (ADS)

    Wren, Stephen P.; Nguyen, T. Hien; Gascoine, Paul; Lacey, Dick; Sun, Tong; Grattan, Kenneth T. V.

    2013-05-01

    A chemical sensor for the detection of cocaine has been developed, based on a molecularly imprinted polymer (MIP) containing a fluorescein moiety as the signalling group. The fluorescent MIP was formed and covalently attached to the distal end of an optical fibre. The sensor exhibited an increase in fluorescence intensity in response to cocaine in an aqueous acetonitrile mixture. Selectivity for cocaine over codeine has been demonstrated.

  10. 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. PMID:26530921

  11. A Strength-Based Approach to Teacher Professional Development

    ERIC Educational Resources Information Center

    Zwart, Rosanne C.; Korthagen, Fred A. J.; Attema-Noordewier, Saskia

    2015-01-01

    Based on positive psychology, self-determination theory and a perspective on teacher quality, this study proposes and examines a strength-based approach to teacher professional development. A mixed method pre-test/post-test design was adopted to study perceived outcomes of the approach for 93 teachers of six primary schools in the Netherlands and…

  12. EFL Reading Instruction: Communicative Task-Based Approach

    ERIC Educational Resources Information Center

    Sidek, Harison Mohd

    2012-01-01

    The purpose of this study was to examine the overarching framework of EFL (English as a Foreign Language) reading instructional approach reflected in an EFL secondary school curriculum in Malaysia. Based on such analysis, a comparison was made if Communicative Task-Based Language is the overarching instructional approach for the Malaysian EFL…

  13. Water models based on a single potential energy surface and different molecular degrees of freedom

    NASA Astrophysics Data System (ADS)

    Saint-Martin, Humberto; Hernández-Cobos, Jorge; Ortega-Blake, Iván

    2005-06-01

    Up to now it has not been possible to neatly assess whether a deficient performance of a model is due to poor parametrization of the force field or the lack of inclusion of enough molecular properties. This work compares several molecular models in the framework of the same force field, which was designed to include many-body nonadditive effects: (a) a polarizable and flexible molecule with constraints that account for the quantal nature of the vibration [B. Hess, H. Saint-Martin, and H. J. C. Berendsen, J. Chem. Phys. 116, 9602 (2002), H. Saint-Martin, B. Hess, and H. J. C. Berendsen, J. Chem. Phys. 120, 11133 (2004)], (b) a polarizable and classically flexible molecule [H. Saint-Martin, J. Hernández-Cobos, M. I. Bernal-Uruchurtu, I. Ortega-Blake, and H. J. C. Berendsen, J. Chem. Phys. 113, 10899 (2000)], (c) a polarizable and rigid molecule, and finally (d) a nonpolarizable and rigid molecule. The goal is to determine how significant the different molecular properties are. The results indicate that all factors—nonadditivity, polarizability, and intramolecular flexibility—are important. Still, approximations can be made in order to diminish the computational cost of the simulations with a small decrease in the accuracy of the predictions, provided that those approximations are counterbalanced by the proper inclusion of an effective molecular property, that is, an average molecular geometry or an average dipole. Hence instead of building an effective force field by parametrizing it in order to reproduce the properties of a specific phase, a building approach is proposed that is based on adequately restricting the molecular flexibility and/or polarizability of a model potential fitted to unimolecular properties, pair interactions, and many-body nonadditive contributions. In this manner, the same parental model can be used to simulate the same substance under a wide range of thermodynamic conditions. An additional advantage of this approach is that, as the force

  14. Application of molecular biology at the approach of Bartter's syndrome: case report.

    PubMed

    Reis, Geisilaine Soares Dos; Miranda, Débora Marques de; Pereira, Paula Cristina de Barros; Sarubi, Helena Cunha; Rodrigues, Luciana Bastos; Marco, Luiz Armando Cunha de; Silva, Ana Cristina Simões E

    2012-03-01

    This paper aims to show the utility of molecular biology for diagnose Bartter syndrome (BS) by the case report of two sisters and to propose a diagram for the molecular approach of this syndrome. The two reported cases presented prematurity, pregnancy complicated with polyhydramnio and low birth weight. During the first year of life, children exhibited polyuria, polydipsia and failure to thrive, leading to the investigation of renal tubular diseases and innate errors of metabolism. The laboratorial exams suggested BS, but the definitive diagnostic was only obtained by the detection of homozygous mutation on the exon 5 of the gene KCNJ1, resulting in a substitution of the aminoacid alanin for valin on codon 214 (A214V) in both DNA stripes in the two sisters and a heterozygous mutation in their parents. The definitive diagnostic of BS is frequently very difficult to be obtained. Consequently, considering the reported cases, we showed the utility of molecular techniques for the definitive diagnostic of BS and we proposed a diagram for the rational use of these techniques. PMID:22441188

  15. Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

    PubMed Central

    Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439

  16. A novel molecular approach for tracing terrigenous dissolved organic matter into the deep ocean

    NASA Astrophysics Data System (ADS)

    Medeiros, Patricia M.; Seidel, Michael; Niggemann, Jutta; Spencer, Robert G. M.; Hernes, Peter J.; Yager, Patricia L.; Miller, William L.; Dittmar, Thorsten; Hansell, Dennis A.

    2016-05-01

    Marine dissolved organic matter (DOM) contains one of the largest exchangeable organic carbon pools on Earth. Riverine input represents an important source of DOM to the oceans, yet much remains to be learned about the fate of the DOM linking terrestrial to oceanic carbon cycles through rivers at the global scale. Here we use ultrahigh-resolution mass spectrometry to identify 184 molecular formulae that are indicators of riverine inputs (referred to as t-Peaks) and to track their distribution in the deep North Atlantic and North Pacific Oceans. The t-Peaks were found to be enriched in the Amazon River, to be highly correlated with known tracers of terrigenous input, and to be observed in all samples from four different rivers characterized by vastly different landscapes and vegetation coverage spanning equatorial (Amazon and Congo), subtropical (Altamaha), and Arctic (Kolyma) regions. Their distribution reveals that terrigenous organic matter is injected into the deep ocean by the global meridional overturning circulation, indicating that a fraction of the terrigenous DOM introduced by rivers contributes to the DOM pool observed in the deep ocean and to the storage of terrigenous organic carbon. This novel molecular approach can be used to further constrain the transfer of DOM from land to sea, especially considering that Fourier transform ion cyclotron resonance mass spectrometer analysis is becoming increasingly frequent in studies characterizing the molecular composition of DOM in lakes, rivers, and the ocean.

  17. Molecular (PCR-DGGE) versus morphological approach: analysis of taxonomic composition of potentially toxic cyanobacteria in freshwater lakes

    PubMed Central

    2014-01-01

    Background The microscopic Utermöhl method is commonly used for the recognition of the presence and taxonomic composition of potentially toxic cyanobacteria and is especially useful for monitoring reservoirs used as drinking water, recreation and fishery resources. However, this method is time-consuming and does not allow potentially toxic and nontoxic cyanobacterial strains to be distinguished. We have developed a method based on denaturing gradient gel electrophoresis (DGGE) of the marker gene ITS and the mcy-gene cluster, and DNA sequencing. We have attempted to calibrate the DGGE-method with a microscopic procedure, using water samples taken in 2011 from four lakes of the Great Mazurian Lakes system. Results Results showed that the classic microscopic method was much more precise and allowed the classification of the majority of cyanobacterial taxa to the species or genus. Using the molecular approach, most of the sequences could only be assigned to a genus or family. The results of DGGE and microscopic analyses overlapped in the detection of the filamentous cyanobacteria. For coccoid cyanobacteria, we only found two taxa using the molecular method, which represented 17% of the total taxa identified using microscopic observations. The DGGE method allowed the identification of two genera of cyanobacteria (Planktothrix and Microcystis) in the studied samples, which have the potential ability to produce toxins from the microcystins group. Conclusions The results confirmed that the molecular approach is useful for the rapid detection and taxonomic distinction of potentially toxic cyanobacteria in lake-water samples, also in very diverse cyanobacterial communities. Such rapid detection is unattainable by other methods. However, with still limited nucleotide sequences deposited in the public databases, this method is currently not sufficient to evaluate the entire taxonomic composition of cyanobacteria in lakes. PMID:24517495

  18. Joint United States-European Union Theoretical and Practical Course on Molecular Approaches for In Situ Biogradation

    SciTech Connect

    Suflita, Joseph M.; Duncan, Kathleen E.

    2010-08-14

    The Joint United States - European Union Theoretical and Practical Course on Molecular Approaches for in situ Biodegradation was held May 24 through June 7 at The University of Oklahoma. Twenty-four graduate and postgraduate students from both the United States and the European Union attended the course. Nine states and ten European countries were represented. Students were assigned living quarters and laboratory partners to maximize interactions between US and EU participants as well as to mix people with different technical backgrounds together. The students used the latest methods in molecular biology to characterize beneficial microorganisms and genes involved in the biodegradation of pollutants at a nearby landfill as well as an active hydrocarbon-producing site, part of which is undergoing bioremediation. Seminars by distinguished scientists were organized to expose the students to the breadth of the environmental field, including field assay and engineering applications, laboratory scale bioreactors, microbiology, genetics, regulation, pathway analysis, design of recombinant bacteria, and application of the associated techniques to the field. Lectures were given by various OU faculty on the principles behind the techniques to be used in the laboratory. These lectures included troubleshooting hints and encouraged questions and comments from the audience. The laboratory experiments covered chemical, microbiological, and molecular genetic analyses of soils; bioavailability of contaminants; enrichment cultures; gene probing; PCR amplification of known genes and gene families; identification of microbes based traditional and nontraditional approaches, nutritional capabilities, and 16S rRNA sequence; mRNA detection; and enzyme assays. Field trips were made to the USGS landfill field sampling site, and to the Tall Grass Prairie Preserve, a Nature Conservancy site which also featured long-term studies of bioremediation of crude oil and brine spills by one of the

  19. Anisotropy induced Kondo splitting in a mechanically stretched molecular junction: A first-principles based study

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoli; Hou, Dong; Zheng, Xiao; Yan, YiJing

    2016-01-01

    The magnetic anisotropy and Kondo phenomena in a mechanically stretched magnetic molecular junction are investigated by combining the density functional theory (DFT) and hierarchical equations of motion (HEOM) approach. The system is comprised of a magnetic complex Co(tpy-SH)2 sandwiched between adjacent gold electrodes, which is mechanically stretched in experiments done by Parks et al. [Science 328, 1370 (2010)]. The electronic structure and mechanical property of the stretched system are investigated via the DFT calculations. The HEOM approach is then employed to characterize the Kondo resonance features, based on the Anderson impurity model parameterized from the DFT results. It is confirmed that the ground state prefers the S = 1 local spin state. The structural properties, the magnetic anisotropy, and corresponding Kondo peak splitting in the axial stretching process are systematically evaluated. The results reveal that the strong electron correlations and the local magnetic properties of the molecule magnet are very sensitive to structural distortion. This work demonstrates that the combined DFT+HEOM approach could be useful in understanding and designing mechanically controlled molecular junctions.

  20. Component design bases - A template approach

    SciTech Connect

    Pabst, L.F. ); Strickland, K.M. )

    1991-01-01

    A well-documented nuclear plant design basis can enhance plant safety and availability. Older plants, however, often lack historical evidence of the original design intent, particularly for individual components. Most plant documentation describes the actual design (what is) rather than the bounding limits of the design. Without knowledge of these design limits, information from system descriptions and equipment specifications is often interpreted as inviolate design requirements. Such interpretations may lead to unnecessary design conservatism in plant modifications and unnecessary restrictions on plant operation. In 1986, Florida Power and Light Company's (FP and L's) Turkey Point plant embarked on one of the first design basis reconstitution programs in the United States to catalog the true design requirements. As the program developed, design basis users expressed a need for additional information at the component level. This paper outlines a structured (template) approach to develop useful component design basis information (including the WHYs behind the design).

  1. Challenges to a molecular approach to prey identification in the Burmese python, Python molurus bivittatus

    USGS Publications Warehouse

    Falk, Bryan; Reed, Robert N.

    2015-01-01

    Molecular approaches to prey identification are increasingly useful in elucidating predator–prey relationships, and we aimed to investigate the feasibility of these methods to document the species identities of prey consumed by invasive Burmese pythons in Florida. We were particularly interested in the diet of young snakes, because visual identification of prey from this size class has proven difficult. We successfully extracted DNA from the gastrointestinal contents of 43 young pythons, as well as from several control samples, and attempted amplification of DNA mini-barcodes, a 130-bp region of COX1. Using a PNA clamp to exclude python DNA, we found that prey DNA was not present in sufficient quality for amplification of this locus in 86% of our samples. All samples from the GI tracts of young pythons contained only hair, and the six samples we were able to identify to species were hispid cotton rats. This suggests that young Burmese pythons prey predominantly on small mammals and that prey diversity among snakes of this size class is low. We discuss prolonged gastrointestinal transit times and extreme gastric breakdown as possible causes of DNA degradation that limit the success of a molecular approach to prey identification in Burmese pythons

  2. Molecular approaches for a better understanding of the epidemiology and population genetics of Leishmania.

    PubMed

    Schönian, G; Kuhls, K; Mauricio, I L

    2011-04-01

    Molecular approaches are being used increasingly for epidemiological studies of visceral and cutaneous leishmaniases. Several molecular markers resolving genetic differences between Leishmania parasites at species and strain levels have been developed to address key epidemiological and population genetic questions. The current gold standard, multilocus enzyme typing (MLEE), needs cultured parasites and lacks discriminatory power. PCR assays identifying species directly with clinical samples have proven useful in numerous field studies. Multilocus sequence typing (MLST) is potentially the most powerful phylogenetic approach and will, most probably, replace MLEE in the future. Multilocus microsatellite typing (MLMT) is able to discriminate below the zymodeme level and seems to be the best candidate for becoming the gold standard for distinction of strains. Population genetic studies by MLMT revealed geographical and hierarchic population structure in L. tropica, L. major and the L. donovani complex. The existence of hybrids and gene flow between Leishmania populations suggests that sexual recombination is more frequent than previously thought. However, typing and analytical tools need to be further improved. Accessible databases should be created and sustained for integrating data obtained by different researchers. This would allow for global analyses and help to avoid biases in analyses due to small sample sizes. PMID:21078222

  3. On the horns of a dilemma: molecular approaches refine ex situ conservation in crisis.

    PubMed

    Russello, Michael A; Amato, George

    2007-06-01

    Seven years into this new millennium, species and habitat loss continue at an accelerated rate. While there have been individual examples of conservation success, the trend towards catastrophic loss of biological diversity persists. If we are to be successful in saving even a handful of critically endangered species, it is clear that they will need to be intensively managed using a variety of in situ and ex situ approaches. The highest profile ex situ conservation strategy is captive breeding. Although its relative role in an overall conservation management plan varies, captive breeding may present the only viable option for propagating the future of a species once rendered extinct in the wild. The study of Iyengar et al. in this issue of Molecular Ecology on one such species, the scimitar-horned oryx (Oryx dammah), represents an important contribution to ex situ conservation, demonstrating how critical insights into demographic history and population genetic structure obtained using molecular approaches may significantly contribute to captive breeding and reintroduction strategies. PMID:17561901

  4. Challenges to a molecular approach to prey identification in the Burmese python, Python molurus bivittatus

    PubMed Central

    Reed, Robert N.

    2015-01-01

    Molecular approaches to prey identification are increasingly useful in elucidating predator–prey relationships, and we aimed to investigate the feasibility of these methods to document the species identities of prey consumed by invasive Burmese pythons in Florida. We were particularly interested in the diet of young snakes, because visual identification of prey from this size class has proven difficult. We successfully extracted DNA from the gastrointestinal contents of 43 young pythons, as well as from several control samples, and attempted amplification of DNA mini-barcodes, a 130-bp region of COX1. Using a PNA clamp to exclude python DNA, we found that prey DNA was not present in sufficient quality for amplification of this locus in 86% of our samples. All samples from the GI tracts of young pythons contained only hair, and the six samples we were able to identify to species were hispid cotton rats. This suggests that young Burmese pythons prey predominantly on small mammals and that prey diversity among snakes of this size class is low. We discuss prolonged gastrointestinal transit times and extreme gastric breakdown as possible causes of DNA degradation that limit the success of a molecular approach to prey identification in Burmese pythons. PMID:26623196

  5. A multi-scale approach to molecular dynamics simulations of shock waves

    SciTech Connect

    Reed, E J; Fried, L E; Manaa, M R; Joannopoulos, J D

    2004-09-03

    Study of the propagation of shock waves in condensed matter has led to new discoveries ranging from new metastable states of carbon [1] to the metallic conductivity of hydrogen in Jupiter, [2] but progress in understanding the microscopic details of shocked materials has been extremely difficult. Complications can include the unexpected formation of metastable states of matter that determine the structure, instabilities, and time-evolution of the shock wave. [1,3] The formation of these metastable states can depend on the time-dependent thermodynamic pathway that the material follows behind the shock front. Furthermore, the states of matter observed in the shock wave can depend on the timescale on which observation is made. [4,1] Significant progress in understanding these microscopic details has been made through molecular dynamics simulations using the popular non-equilibrium molecular dynamics (NEMD) approach to atomistic simulation of shock compression. [5] The NEMD method involves creating a shock at one edge of a large system by assigning some atoms at the edge a fixed velocity. The shock propagates across the computational cell to the opposite side. The computational work required by NEMD scales at least quadratically in the evolution time because larger systems are needed for longer simulations to prevent the shock wave from reflecting from the edge of the computational cell and propagating back into the cell. When quantum mechanical methods with poor scaling of computational effort with system size are employed, this approach to shock simulations rapidly becomes impossible.

  6. Challenges to a molecular approach to prey identification in the Burmese python, Python molurus bivittatus.

    PubMed

    Falk, Bryan G; Reed, Robert N

    2015-01-01

    Molecular approaches to prey identification are increasingly useful in elucidating predator-prey relationships, and we aimed to investigate the feasibility of these methods to document the species identities of prey consumed by invasive Burmese pythons in Florida. We were particularly interested in the diet of young snakes, because visual identification of prey from this size class has proven difficult. We successfully extracted DNA from the gastrointestinal contents of 43 young pythons, as well as from several control samples, and attempted amplification of DNA mini-barcodes, a 130-bp region of COX1. Using a PNA clamp to exclude python DNA, we found that prey DNA was not present in sufficient quality for amplification of this locus in 86% of our samples. All samples from the GI tracts of young pythons contained only hair, and the six samples we were able to identify to species were hispid cotton rats. This suggests that young Burmese pythons prey predominantly on small mammals and that prey diversity among snakes of this size class is low. We discuss prolonged gastrointestinal transit times and extreme gastric breakdown as possible causes of DNA degradation that limit the success of a molecular approach to prey identification in Burmese pythons. PMID:26623196

  7. Context-Based Chemistry: The Salters Approach

    ERIC Educational Resources Information Center

    Bennett, Judith; Lubben, Fred

    2006-01-01

    This paper describes briefly the development and key features of one of the major context-based courses for upper high school students, Salters Advanced Chemistry. It goes on to consider the research evidence on the impact of the course, focusing on teachers' views, and, in particular, on students' affective and cognitive responses. The research…

  8. PBL Approach in Web-Based Instruction

    ERIC Educational Resources Information Center

    ChanLin, Lih-Juan; Chan, Kung-Chi

    2004-01-01

    Web-Based Instruction is increasingly being recognized as a means of teaching and learning. In dietetics, the interactions between drugs and nutrients are complex due to the wide variety of drugs and their mechanism and interactions with nutrients. How to help student professionals acquired necessary skills and knowledge is important in a dietetic…

  9. A model-based multisensor data fusion knowledge management approach

    NASA Astrophysics Data System (ADS)

    Straub, Jeremy

    2014-06-01

    A variety of approaches exist for combining data from multiple sensors. The model-based approach combines data based on its support for or refutation of elements of the model which in turn can be used to evaluate an experimental thesis. This paper presents a collection of algorithms for mapping various types of sensor data onto a thesis-based model and evaluating the truth or falsity of the thesis, based on the model. The use of this approach for autonomously arriving at findings and for prioritizing data are considered. Techniques for updating the model (instead of arriving at a true/false assertion) are also discussed.

  10. A molecular approach to study the arbuscular mycorrhizal fungi community in a typical Piedmont grapevine cultivar

    NASA Astrophysics Data System (ADS)

    Magurno, F.; Bughi Peruglia, G.; Lumini, E.; Bianciotto, V.; Balestrini, R.

    2009-04-01

    Viticulture and wine production represent one of the most relevant agro-food sectors for the Piedmont Region (Italy) in terms of value, with more than 400 millions € a year (12 % of total agricultural production of the Region and the 10 % of the national grape and wine production). The soil where grapevines (Vitis spp.) grow is one of the first parameters influencing the complex grapevine-wine chain. Arbuscular mycorrhizal fungi (AMFs), a main component of soil microbiota in most agrosystems, are considered crucial biomarkers of soil quality because of their biofertilisers role. As mutualistic symbionts, they colonize the roots of the majority of plants. Benefits in symbiosis are well showed as an improvement in shoot/root growth, mineral transport, water-stress tolerance and resistance to certain diseases. Grapevines roots are often heavily colonized by AMFs under field conditions and in some cases AMFs appear to be necessary for their normal growth and survival. Even so, little information are until now available about composition of AMFs communities living in the vineyards soil and in associations with grapevine roots, mainly related to morphological characterization. Vineyard of Nebbiolo, one of the most important Piedmont cultivar, was selected in order to study the AMFs community using a molecular approach. Soil samples and roots from an experimental vineyard located in Lessona (Biella, Piedmont, Italy) were analyzed using AM fungal-specific primers to partially amplify the small subunit (SSU) of the ribosomal DNA genes. Much more than 650 clones were sequenced. Phylogenetic analyses identified 32 OTUs from soil, clustered into Glomus groups Aa, Ab, Ad and B, Diversisporaceae and Gigasporaceae families. Thirteen OTUs from roots were determined, clustered into Glomus groups Ab, Ad and B, and Gigasporaceae family. In particular, Glomus group Ad was the best represented in both compartments, suggesting a correlation between intra and extra radical communities

  11. A comparison of morphological and molecular-based surveys to estimate the species richness of Chaetoceros and Thalassiosira (bacillariophyta), in the Bay of Fundy.

    PubMed

    Hamsher, Sarah E; LeGresley, Murielle M; Martin, Jennifer L; Saunders, Gary W

    2013-01-01

    The goal of this study was to compare the ability of morphology and molecular-based surveys to estimate species richness for two species-rich diatom genera, Chaetoceros Ehrenb. and Thalassiosira Cleve, in the Bay of Fundy. Phytoplankton tows were collected from two sites at intervals over two years and subsampled for morphology-based surveys (2010, 2011), a culture-based DNA reference library (DRL; 2010), and a molecular-based survey (2011). The DRL and molecular-based survey utilized the 3' end of the RUBISCO large subunit (rbcL-3P) to identify genetic species groups (based on 0.1% divergence in rbcL-3P), which were subsequently identified morphologically to allow comparisons to the morphology-based survey. Comparisons were compiled for the year (2011) by site (n = 2) and by season (n = 3). Of the 34 taxa included in the comparisons, 50% of taxa were common to both methods, 35% were unique to the molecular-based survey, and 12% were unique to the morphology-based survey, while the remaining 3% of taxa were unidentified genetic species groups. The morphology-based survey excelled at identifying rare taxa in individual tow subsamples, which were occasionally missed with the molecular approach used here, while the molecular methods (the DRL and molecular-based survey), uncovered nine cryptic species pairs and four previously overlooked species. The last mentioned were typically difficult to identify and were generically assigned to Thalassiosira spp. during the morphology-based survey. Therefore, for now we suggest a combined approach encompassing routine morphology-based surveys accompanied by periodic molecular-based surveys to monitor for cryptic and difficult to identify taxa. As sequencing technologies improve, molecular-based surveys should become routine, leading to a more accurate representation of species composition and richness in monitoring programs. PMID:24130665

  12. GRID-based three-dimensional pharmacophores I: FLAPpharm, a novel approach for pharmacophore elucidation.

    PubMed

    Cross, Simon; Baroni, Massimo; Goracci, Laura; Cruciani, Gabriele

    2012-10-22

    Pharmacophore elucidation approaches are routinely used in drug discovery, primarily with the aim of determining the three-dimensional arrangement of common features shared by ligands interacting at the site of interest; these features can then be used to investigate the structure-activity relationship between the ligands and also to screen for other molecules possessing the relevant features. Here we present a novel approach based on GRID molecular interaction fields and the derivative method FLAP that has been previously described, which provides a common reference framework to compare both small molecule ligands and macromolecular protein targets. Unlike classical pharmacophore elucidation approaches that extract simplistic molecular features, determine those which are common across the data set, and use these features to align the structures, FLAPpharm first aligns the structures and subsequently extracts the common interacting features in terms of their molecular interaction fields, pseudofields, and atomic points, representing the common pharmacophore as a more comprehensive pharmacophoric pseudomolecule. The approach is applied to a number of data sets to investigate performance in terms of reproducing the X-ray crystallography-based alignment, in terms of its discriminatory ability when applied to virtual screening and also to illustrate its ability to explain alternative binding modes. In part two of this publication, a comprehensive benchmark data set for pharmacophore elucidation is presented and the performance of FLAPpharm discussed. PMID:22970894

  13. 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.

  14. Accurate vibrational spectra via molecular tailoring approach: A case study of water clusters at MP2 level

    NASA Astrophysics Data System (ADS)

    Sahu, Nityananda; Gadre, Shridhar R.

    2015-01-01

    In spite of the recent advents in parallel algorithms and computer hardware, high-level calculation of vibrational spectra of large molecules is still an uphill task. To overcome this, significant effort has been devoted to the development of new algorithms based on fragmentation methods. The present work provides the details of an efficient and accurate procedure for computing the vibrational spectra of large clusters employing molecular tailoring approach (MTA). The errors in the Hessian matrix elements and dipole derivatives arising due to the approximation nature of MTA are reduced by grafting the corrections from a smaller basis set. The algorithm has been tested out for obtaining vibrational spectra of neutral and charged water clusters at Møller-Plesset second order level of theory, and benchmarking them against the respective full calculation (FC) and/or experimental results. For (H2O)16 clusters, the estimated vibrational frequencies are found to differ by a maximum of 2 cm-1 with reference to the corresponding FC values. Unlike the FC, the MTA-based calculations including grafting procedure can be performed on a limited hardware, yet take a fraction of the FC time. The present methodology, thus, opens a possibility of the accurate estimation of the vibrational spectra of large molecular systems, which is otherwise impossible or formidable.

  15. Accurate vibrational spectra via molecular tailoring approach: a case study of water clusters at MP2 level.

    PubMed

    Sahu, Nityananda; Gadre, Shridhar R

    2015-01-01

    In spite of the recent advents in parallel algorithms and computer hardware, high-level calculation of vibrational spectra of large molecules is still an uphill task. To overcome this, significant effort has been devoted to the development of new algorithms based on fragmentation methods. The present work provides the details of an efficient and accurate procedure for computing the vibrational spectra of large clusters employing molecular tailoring approach (MTA). The errors in the Hessian matrix elements and dipole derivatives arising due to the approximation nature of MTA are reduced by grafting the corrections from a smaller basis set. The algorithm has been tested out for obtaining vibrational spectra of neutral and charged water clusters at Møller-Plesset second order level of theory, and benchmarking them against the respective full calculation (FC) and/or experimental results. For (H2O)16 clusters, the estimated vibrational frequencies are found to differ by a maximum of 2 cm(-1) with reference to the corresponding FC values. Unlike the FC, the MTA-based calculations including grafting procedure can be performed on a limited hardware, yet take a fraction of the FC time. The present methodology, thus, opens a possibility of the accurate estimation of the vibrational spectra of large molecular systems, which is otherwise impossible or formidable. PMID:25573553

  16. Structural Assembly of Molecular Complexes Based on Residual Dipolar Couplings

    PubMed Central

    Berlin, Konstantin; O’Leary, Dianne P.; Fushman, David

    2010-01-01

    We present and evaluate a rigid-body molecular docking method, called PATIDOCK, that relies solely on the three-dimensional structure of the individual components and the experimentally derived residual dipolar couplings (RDC) for the complex. We show that, given an accurate ab initio predictor of the alignment tensor from a protein structure, it is possible to accurately assemble a protein-protein complex by utilizing the RDC’s sensitivity to molecular shape to guide the docking. The proposed docking method is robust against experimental errors in the RDCs and computationally efficient. We analyze the accuracy and efficiency of this method using experimental or synthetic RDC data for several proteins, as well as synthetic data for a large variety of protein-protein complexes. We also test our method on two protein systems for which the structure of the complex and steric-alignment data are available (Lys48-linked diubiquitin and a complex of ubiquitin and a ubiquitin-associated domain) and analyze the effect of flexible unstructured tails on the outcome of docking. The results demonstrate that it is fundamentally possible to assemble a protein-protein complex based solely on experimental RDC data and the prediction of the alignment tensor from three-dimensional structures. Thus, despite the purely angular nature of residual dipolar couplings, they can be converted into intermolecular distance/translational constraints. Additionally we show a method for combining RDCs with other experimental data, such as ambiguous constraints from interface mapping, to further improve structure characterization of the protein complexes. PMID:20550109

  17. Molecular bases of proliferation of Francisella tularensis in Arthropod vectors

    PubMed Central

    Asare, Rexford; Akimana, Christine; Jones, Snake; Kwaik, Yousef Abu

    2010-01-01

    Summary Arthropod vectors are important vehicles for transmission of Francisella tularensis between mammals, but very little is known about the F. tularensis-arthropod vector interaction. Drosophila melanogaster has been recently developed as an arthropod vector model for F. tularensis. We have shown that intracellular trafficking of F. tularensis within human monocytes-derived macrophages and D. melanogaster-derived S2 cells is very similar. Within both evolutionarily distant host cells, the Francisella-containing phagosome matures to a late endosome-like phagosome with limited fusion to lysosomes followed by rapid bacterial escape into the cytosol where the bacterial proliferate. To decipher the molecular bases of intracellular proliferation of F. tularensis within arthropod-derived cells, we screened a comprehensive library of mutants of F. tularensis subsp novicida for their defect in intracellular proliferation within D. melanogaster-derived S2 cells. Our data show that 394 genes, representing 22% of the genome, are required for intracellular proliferation within D. melanogaster-derived S2 cells, including many of the Francisella Pathogenicity Island (FPI) genes that are also required for proliferation within mammalian macrophages. Functional gene classes that exhibit growth defect include metabolic (25%), FPI (2%), Type IV pili (1%), transport (16%) and DNA modification (5%). Among 168 most defective mutants in intracellular proliferation in S2 cells, 80 are defective in lethality and proliferation within adult D. melanogaster. The observation that only 135 of the 394 mutants that are defective in S2 cells are also defective in human macrophages indicates that F. tularensis utilize common as well as distinct mechanisms to proliferate within mammalian and arthropod cells. Our studies will facilitate deciphering the molecular aspects of F. tularensis-arthropod vector interaction and its patho-adaptation to infect mammals. PMID:20482589

  18. Molecular marker approaches for tracking redox damage and protection in keratins.

    PubMed

    Dyer, Jolon M; Cornellison, Charisa D; Grosvenor, Anita J; Clerens, Stefan; Deb-Choudhury, Santanu

    2014-01-01

    There is increasing awareness of the importance of reductive and oxidative (redox) protein damage in protein-based materials including, hair, wool, nails, and skin. Light-induced damage to protein-based materials is of particular concern because of its impact on age-related degradation and product life spans. Consequently, cosmetic applications frequently target hair and skin restoration, where the integrity of the constituent filamentous proteins is essential to a healthy appearance. The keratins constitute an important subset of the structural proteins within skin, hair, and wool. We will introduce a means to assess damage to this important group of proteins at the molecular level, utilizing proteomic techniques to track the formation or degradation of sensitive peptides within intermediate filament proteins. The degradation of three molecular markers of redox damage, the peptides SFGYR, LASDDFR, and DVEEWYIR, along with the formation of their oxidized products, is demonstrated after exposure to ultraviolet A, ultraviolet B, and blue light. The method is shown to be suitable for evaluating the protective effect of treatments, as lower levels of oxidative markers were observed after the application of a protective fiber treatment. Molecular-level redox tracking will allow more targeted design and evaluation of protection and repair treatments for protein systems. PMID:24602820

  19. Communication: Energy-dependent resonance broadening in symmetric and asymmetric molecular junctions from an ab initio non-equilibrium Green's function approach

    NASA Astrophysics Data System (ADS)

    Liu, Zhen-Fei; Neaton, Jeffrey B.

    2014-10-01

    The electronic structure of organic-inorganic interfaces often features resonances originating from discrete molecular orbitals coupled to continuum lead states. An example is molecular junction, individual molecules bridging electrodes, where the shape and peak energy of such resonances dictate junction conductance, thermopower, I-V characteristics, and related transport properties. In molecular junctions where off-resonance coherent tunneling dominates transport, resonance peaks in the transmission function are often assumed to be Lorentzian functions with an energy-independent broadening parameter Γ. Here we define a new energy-dependent resonance broadening function, Γ(E), based on diagonalization of non-Hermitian matrices, which can describe resonances of a more complex, non-Lorentzian nature and can be decomposed into components associated with the left and right leads, respectively. We compute this quantity via an ab initio non-equilibrium Green's function (NEGF) approach based on density functional theory (DFT) for both symmetric and asymmetric molecular junctions, and show that our definition of Γ(E), when combined with Breit-Wigner formula, reproduces the transmission calculated from DFT-NEGF. Through a series of examples, we illustrate how this approach can shed new light on experiments and understanding of junction transport properties in terms of molecular orbitals.

  20. Communication: energy-dependent resonance broadening in symmetric and asymmetric molecular junctions from an ab initio non-equilibrium Green's function approach.

    PubMed

    Liu, Zhen-Fei; Neaton, Jeffrey B

    2014-10-01

    The electronic structure of organic-inorganic interfaces often features resonances originating from discrete molecular orbitals coupled to continuum lead states. An example is molecular junction, individual molecules bridging electrodes, where the shape and peak energy of such resonances dictate junction conductance, thermopower, I-V characteristics, and related transport properties. In molecular junctions where off-resonance coherent tunneling dominates transport, resonance peaks in the transmission function are often assumed to be Lorentzian functions with an energy-independent broadening parameter Γ. Here we define a new energy-dependent resonance broadening function, Γ(E), based on diagonalization of non-Hermitian matrices, which can describe resonances of a more complex, non-Lorentzian nature and can be decomposed into components associated with the left and right leads, respectively. We compute this quantity via an ab initio non-equilibrium Green's function (NEGF) approach based on density functional theory (DFT) for both symmetric and asymmetric molecular junctions, and show that our definition of Γ(E), when combined with Breit-Wigner formula, reproduces the transmission calculated from DFT-NEGF. Through a series of examples, we illustrate how this approach can shed new light on experiments and understanding of junction transport properties in terms of molecular orbitals. PMID:25296777

  1. Communication: Energy-dependent resonance broadening in symmetric and asymmetric molecular junctions from an ab initio non-equilibrium Green's function approach

    SciTech Connect

    Liu, Zhen-Fei; Neaton, Jeffrey B.

    2014-10-07

    The electronic structure of organic-inorganic interfaces often features resonances originating from discrete molecular orbitals coupled to continuum lead states. An example is molecular junction, individual molecules bridging electrodes, where the shape and peak energy of such resonances dictate junction conductance, thermopower, I-V characteristics, and related transport properties. In molecular junctions where off-resonance coherent tunneling dominates transport, resonance peaks in the transmission function are often assumed to be Lorentzian functions with an energy-independent broadening parameter Γ. Here we define a new energy-dependent resonance broadening function, Γ(E), based on diagonalization of non-Hermitian matrices, which can describe resonances of a more complex, non-Lorentzian nature and can be decomposed into components associated with the left and right leads, respectively. We compute this quantity via an ab initio non-equilibrium Green's function (NEGF) approach based on density functional theory (DFT) for both symmetric and asymmetric molecular junctions, and show that our definition of Γ(E), when combined with Breit-Wigner formula, reproduces the transmission calculated from DFT-NEGF. Through a series of examples, we illustrate how this approach can shed new light on experiments and understanding of junction transport properties in terms of molecular orbitals.

  2. [Evidence-based medicine: an epistemological approach].

    PubMed

    Henao, Daniel Eduardo; Jaimes, Fabián Alberto

    2009-03-01

    Evidence-based medicine gathers physician's experience and the best scientific evidence to make medical decisions. This proposal has been widely promulgated by medical opinion leaders. Despite a large literature supporting this practice, a formal discussion has not been established regarding its epistemological consequences in daily medical work. The main proposal of evidence-based medicine consists of choosing the best medical decision according to the best available results from scientific studies. Herein, the goal was to highlight inappropriate application of the scientific method used by physics to clinical science. The inaccuracy resides in describing health and disease in strictly numeric equivalents that can be homogenized on a continuous scale. Finally, the authors consider each diseased human being as a complex system, unique and particular, and that this being is defined by an historical background as well as current actual context. Therefore, evidence-based medicine possesses certain limitations that must be recognized in order to to provide better health care to patients. PMID:19753837

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

    PubMed

    Lei, Beilei; Liu, Jiyuan; Yao, Xiaojun

    2015-12-01

    Brassinosteroid (BR) phytohormones play indispensable roles in plant growth and development. Brassinolide (BL) and 24-epibrassinolide (24-epiBL) are the most active ones among the BRs reported thus far. Unfortunately, the extremely low natural content and intricate synthesis process limit their popularization in agricultural production. Earlier reports to discover alternative compounds have resulted in molecules with nearly same scaffold structure and without diversity in chemical space. In the present study, receptors structure based BRs regulation mechanism was analyzed. First, we examined the detailed binding interactions and their dynamic stability between BL and its receptor BRI1 and co-receptor BAK1. Then, the binding modes and binding free energies for 24-epiBL and a series of representative BRs binding with BRI1 and BRI1-BAK1 were carried out by molecular docking, energy minimization and MM-PBSA free energy calculation. The obtained binding structures and energetic results provided vital insights into the structural factors affecting the activity from both receptors and BRs aspects. Subsequently, the obtained knowledge will serve as valuable guidance to build pharmacophore models for rational screening of new scaffold alternative BRs. PMID:26362600

  4. Maintain rigid structures in Verlet based Cartesian molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

    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.

  5. 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.

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

    PubMed

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

    2015-12-14

    This paper describes a method to fabricate a microfluidic top-electrode that can be utilized to generate arrays of self-assembled monolayer (SAM)-based junctions. The top-electrodes consist of a liquid-metal of GaOx/EGaIn mechanically stabilized in microchannels and through-holes in polydimethylsiloxane (PDMS); these top-electrodes form molecular junctions by directly placing them onto the SAM supported by template-stripped (TS) Ag or Au bottom-electrodes. Unlike conventional techniques to form multiple junctions, our method does not require lithography to pattern the bottom-electrode and is compatible with TS bottom-electrodes, which are ultra-flat with large grains, free from potential contamination of photoresist residues, and do not have electrode-edges where the molecules are unable to pack well. We formed tunneling junctions with n-alkanethiolate SAMs in yields of ∼80%, with good reproducibility and electrical stability. Temperature dependent J(V) measurements indicated that the mechanism of charge transport across the junction is coherent tunneling. To demonstrate the usefulness of these junctions, we formed molecular diodes based on SAMs with Fc head groups. These junctions rectify currents with a rectification ratio R of 45. These molecular diodes were incorporated in simple electronic circuitry to demonstrate molecular diode-based Boolean logic. PMID:26537895

  7. A novel approach in controlling the conductivity of thin films using molecular layer deposition

    NASA Astrophysics Data System (ADS)

    Lushington, Andrew; Liu, Jian; Bannis, Mohammad N.; Xiao, Biwei; Lawes, Stephen; Li, Ruying; Sun, Xueliang

    2015-12-01

    Here we present a novel way to grow aluminum alkoxide films with tunable conductivity with molecular level accuracy with the use of molecular layer deposition (MLD). Alternating exposures of trimethylaluminum (TMA), ethylene glycol (EG), and terephthaloyl chloride (TC) are used to grow the aluminium alkoxide films. Control over film composition was accomplished by alternating cycles of EG and TC between cycles of TMA and EG. In this fashion the aluminum to carbon ratio can be accurately controlled. These films were then pyrolyzed under a reducing atmosphere to yield a conductive Al2O3/carbon composite. Raman spectroscopy determined that nanocrystalline sp2-graphitic carbon was formed following pyrolysis while sheet resistance measurements determined that conductivity of the film is directly related to aluminium-carbon ratio. To further elucidate the origin of conductivity within the film, synchrotron based XPS was performed.

  8. Concepts for the Formation of Molecular Nanostructures: Self-Assembly and SPM Manipulation -- A Combined Approach.

    NASA Astrophysics Data System (ADS)

    Jung, Thomas A.

    1996-03-01

    We(Work performed in collaboration with J.K. Gimzewski and R. R. Schlittler, IBM Rüschlikon, and C. Joachim and Hao Tang, CNRS Toulouse,) (Supported by the BBW of Switzerland through the ESPRIT basic research program PRONANO (8523). ) demonstrate the controlled generation of molecular nanostructures based on specific chemical synthesis and well-controlled epitaxial growth. Such structures, assembled in parallel by growth kinetics, can be modified selectively by manipulating individual molecules using different modes of the scanning tunneling microscope. The influence of molecular structure on such properties as mobility, conformational adaptation to the substrate, and the current/voltage (I/V) characteristic are compared for porphyrin molecules with different substituents. Numerical simulations are related to experimentally accessible parameters. The resulting rules and concepts are to be generalized and applied to the design of nanostructures having more specific functional properties.

  9. Wavelet-based approach to character skeleton.

    PubMed

    You, Xinge; Tang, Yuan Yan

    2007-05-01

    Character skeleton plays a significant role in character recognition. The strokes of a character may consist of two regions, i.e., singular and regular regions. The intersections and junctions of the strokes belong to singular region, while the straight and smooth parts of the strokes are categorized to regular region. Therefore, a skeletonization method requires two different processes to treat the skeletons in theses two different regions. All traditional skeletonization algorithms are based on the symmetry analysis technique. The major problems of these methods are as follows. 1) The computation of the primary skeleton in the regular region is indirect, so that its implementation is sophisticated and costly. 2) The extracted skeleton cannot be exactly located on the central line of the stroke. 3) The captured skeleton in the singular region may be distorted by artifacts and branches. To overcome these problems, a novel scheme of extracting the skeleton of character based on wavelet transform is presented in this paper. This scheme consists of two main steps, namely: a) extraction of primary skeleton in the regular region and b) amendment processing of the primary skeletons and connection of them in the singular region. A direct technique is used in the first step, where a new wavelet-based symmetry analysis is developed for finding the central line of the stroke directly. A novel method called smooth interpolation is designed in the second step, where a smooth operation is applied to the primary skeleton, and, thereafter, the interpolation compensation technique is proposed to link the primary skeleton, so that the skeleton in the singular region can be produced. Experiments are conducted and positive results are achieved, which show that the proposed skeletonization scheme is applicable to not only binary image but also gray-level image, and the skeleton is robust against noise and affine transform. PMID:17491454

  10. Arts-based and creative approaches to dementia care.

    PubMed

    McGreevy, Jessica

    2016-02-01

    This article presents a review of arts-based and creative approaches to dementia care as an alternative to antipsychotic medications. While use of antipsychotics may be appropriate for some people, the literature highlights the success of creative approaches and the benefits of their lack of negative side effects associated with antipsychotics. The focus is the use of biographical approaches, music, dance and movement to improve wellbeing, enhance social networks, support inclusive practice and enable participation. Staff must be trained to use these approaches. A case study is presented to demonstrate how creative approaches can be implemented in practice and the outcomes that can be expected when used appropriately. PMID:26938607

  11. Differentiating between rights-based and relational ethical approaches.

    PubMed

    Trobec, Irena; Herbst, Majda; Zvanut, Bostjan

    2009-05-01

    When forced treatment in mental health care is under consideration, two approaches guide clinicians in their actions: the dominant rights-based approach and the relational ethical approach. We hypothesized that nurses with bachelor's degrees differentiate better between the two approaches than nurses without a degree. To test this hypothesis a survey was performed in major Slovenian health institutions. We found that nurses emphasize the importance of ethics and personal values, but 55.4% of all the nurse participants confused the two approaches. The results confirmed our hypothesis and indicate the importance of nurses' formal education, especially when caring for patients with mental illness. PMID:19372123

  12. Molecular dynamics as a foundation for flux prediction through nanoporous membranes: A vectorized, constraint-free approach to conservative simulations

    NASA Astrophysics Data System (ADS)

    Inman, Matthew Clay

    A novel, open-cathode direct methanol fuel cell (DMFC ) has been designed and built by researchers at the University of North Florida and University of Florida. Foremost among the advances of this system over previous DMFC architectures is a passive water recovery system which allows product water to replenish that consumed at the anode. This is enabled by a specially-designed water pathway combined with a liquid barrier layer (LBL ). The LBL membrane is positioned between the cathode catalyst layer and the cathode gas diffusion layer, and must exhibit high permeability and low diffusive resistance to both oxygen and water vapor, bulk hydrophobicity to hold back the product liquid water, and must remain electrically conductive. Maintaining water balance at optimum operating temperatures is problematic with the current LBL design, forcing the system to run at lower temperatures decreasing the overall system efficiency. This research presents a novel approach to nanoporous membrane design whereby flux of a given species is determined based upon the molecular properties of said species and those of the diffusing medium, the pore geometry, and the membrane thickness. A molecular dynamics (MD ) model is developed for tracking Knudsen regime flows of a Lennard-Jones (LJ ) fluid through an atomistic pore structure, hundreds of thousands of wall collision simulations are performed on the University of Florida HiPerGator supercomputer, and the generated trajectory information is used to develop number density and axial velocity profiles for use in a rigorous approach to total flux calculation absent in previously attempted MD models. Results are compared to other published approaches and diffusion data available in the literature. The impact of this study on various applications of membrane design is discussed and additional simulations and model improvements are outlined for future consideration.

  13. 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

  14. 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

    2016-01-01

    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

  15. A new approach to calculate charge carrier transport mobility in organic molecular crystals from imaginary time path integral simulations.

    PubMed

    Song, Linze; Shi, Qiang

    2015-05-01

    We present a new non-perturbative method to calculate the charge carrier mobility using the imaginary time path integral approach, which is based on the Kubo formula for the conductivity, and a saddle point approximation to perform the analytic continuation. The new method is first tested using a benchmark calculation from the numerical exact hierarchical equations of motion method. Imaginary time path integral Monte Carlo simulations are then performed to explore the temperature dependence of charge carrier delocalization and mobility in organic molecular crystals (OMCs) within the Holstein and Holstein-Peierls models. The effects of nonlocal electron-phonon interaction on mobility in different charge transport regimes are also investigated. PMID:25956086

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  17. Ameliorated GA approach for base station planning

    NASA Astrophysics Data System (ADS)

    Wang, Andong; Sun, Hongyue; Wu, Xiaomin

    2011-10-01

    In this paper, we aim at locating base station (BS) rationally to satisfy the most customs by using the least BSs. An ameliorated GA is proposed to search for the optimum solution. In the algorithm, we mesh the area to be planned according to least overlap length derived from coverage radius, bring into isometric grid encoding method to represent BS distribution as well as its number and develop select, crossover and mutation operators to serve our unique necessity. We also construct our comprehensive object function after synthesizing coverage ratio, overlap ratio, population and geographical conditions. Finally, after importing an electronic map of the area to be planned, a recommended strategy draft would be exported correspondingly. We eventually import HongKong, China to simulate and yield a satisfactory solution.

  18. Engineering application based on fuzzy approach

    NASA Astrophysics Data System (ADS)

    Pislaru, Marius; Avasilcai, Silvia; Trandabat, Alexandru

    2011-12-01

    The article focus on an application of chemical engineering. A fuzzy modeling methodology designed to determinate two relevant characteristics of a chemical compound (ferrocenylsiloxane polyamide) for self-assembling - surface tension and maximum UV absorbance measured as temperature and concentration functions. One of the most important parts of a fuzzy rule-based inference system for the polyamide solution characteristics determinations is that it allows to interpret the knowledge contained in the model and also to improve it with a-priori knowledge. The results obtained through proposed method are highly accurate and its can be optimized by utilizing the available information during the modeling process. The results showed that it is feasible in theory and reliable on calculation applying Mamdani fuzzy inference system to the estimation of optical and surface properties of a polyamide solution.

  19. Engineering application based on fuzzy approach

    NASA Astrophysics Data System (ADS)

    Pislaru, Marius; Avasilcai, Silvia; Trandabat, Alexandru

    2012-01-01

    The article focus on an application of chemical engineering. A fuzzy modeling methodology designed to determinate two relevant characteristics of a chemical compound (ferrocenylsiloxane polyamide) for self-assembling - surface tension and maximum UV absorbance measured as temperature and concentration functions. One of the most important parts of a fuzzy rule-based inference system for the polyamide solution characteristics determinations is that it allows to interpret the knowledge contained in the model and also to improve it with a-priori knowledge. The results obtained through proposed method are highly accurate and its can be optimized by utilizing the available information during the modeling process. The results showed that it is feasible in theory and reliable on calculation applying Mamdani fuzzy inference system to the estimation of optical and surface properties of a polyamide solution.

  20. Multiresolution approach based on projection matrices

    SciTech Connect

    Vargas, Javier; Quiroga, Juan Antonio

    2009-03-01

    Active triangulation measurement systems with a rigid geometric configuration are inappropriate for scanning large objects with low measuring tolerances. The reason is that the ratio between the depth recovery error and the lateral extension is a constant that depends on the geometric setup. As a consequence, measuring large areas with low depth recovery error requires the use of multiresolution techniques. We propose a multiresolution technique based on a camera-projector system previously calibrated. The method consists of changing the camera or projector's parameters in order to increase the system depth sensitivity. A subpixel retroprojection error in the self-calibration process and a decrease of approximately one order of magnitude in the depth recovery error can be achieved using the proposed method.