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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.

  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.

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

    PubMed

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

    2002-09-30

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

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

    PubMed

    Hartman, Joshua D; Beran, Gregory J O

    2014-11-11

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

  5. 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.

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

    PubMed

    Salmenkova, E A

    2013-01-01

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

  7. XML-based approaches for the integration of heterogeneous bio-molecular data

    PubMed Central

    Mesiti, Marco; Jiménez-Ruiz, Ernesto; Sanz, Ismael; Berlanga-Llavori, Rafael; Perlasca, Paolo; Valentini, Giorgio; Manset, David

    2009-01-01

    Background The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. Results In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. Conclusion XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources. PMID:19828083

  8. A molecular approach to the Kondo problem in Carbon based systems

    NASA Astrophysics Data System (ADS)

    Soriano, Maria; Jacob, David; Palacios, Juan Jose

    2014-03-01

    There has been a great effort in recent years to understand the emerging Kondo-like resonances in different magnetic molecules such as MnPc. Theoretical approaches based on atomic models have proven to be very useful for the study of this phenomenon when the magnetic moment is essentially localized on a magnetic atom. Nevertheless the Kondo effect can arise in pure carbon-based systems as has been demonstrated experimentally in fullerenes and carbon nanotubes. In this communication we present a multiorbital Anderson model where the orbitals are not atomic but molecular orbitals. This model is fully obtained from Density Functional Theory calculation in combination with Green's functions methodologies. Standard impurity solver techniques are used to solve the model which is applied to fullerenes and other nanographene structures.

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

    PubMed Central

    Pontes, Arthur H.; de Sousa, Marcelo V.

    2016-01-01

    The central nervous system is responsible for an array of cognitive functions such as memory, learning, language, and attention. These processes tend to take place in distinct brain regions; yet, they need to be integrated to give rise to adaptive or meaningful behavior. Since cognitive processes result from underlying cellular and molecular changes, genomics and transcriptomics assays have been applied to human and animal models to understand such events. Nevertheless, genes and RNAs are not the end products of most biological functions. In order to gain further insights toward the understanding of brain processes, the field of proteomics has been of increasing importance in the past years. Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS) have enabled the identification and quantification of thousands of proteins with high accuracy and sensitivity, fostering a revolution in the neurosciences. Herein, we review the molecular bases of explicit memory in the hippocampus. We outline the principles of mass spectrometry (MS)-based proteomics, highlighting the use of this analytical tool to study memory formation. In addition, we discuss MS-based targeted approaches as the future of protein analysis. PMID:27790611

  10. A molecular biology-based approach to resolve the subunit orientation of lipoprotein lipase

    PubMed Central

    Wong, Howard; Yang, Dawn; Hill, John S.; Davis, Richard C.; Nikazy, Judith; Schotz, Michael C.

    1997-01-01

    The subunit orientation of a dimeric enzyme influences the mechanism of action and function. To determine the subunit arrangement of lipoprotein lipase (LPL), a molecular biology-based approach was initiated. An eight amino acid linker region was engineered between two LPL monomers and expressed in COS-7 cells. The resultant tandem-repeat molecule (LPLTR) was lipolytically active and had kinetic parameters, salt inhibition, cofactor-dependent activity, heparin-binding characteristics, and a functional unit size very similar to the expressed native human enzyme. By these criteria, LPLTR was the functional equivalent of native LPL. Considering the length of the linker peptide (no more than 24 Å), monomers in the tethered molecule were restricted to a head-to-tail subunit arrangement. Since LPLTR demonstrated native enzyme-like properties while constrained to this subunit arrangement, these results provide the first compelling evidence that native LPL monomers are arranged in a head-to-tail subunit orientation within the active dimer. Thus, LPL function in physiology, lipolysis, and binding to cell-surface components must now be addressed with this subunit orientation in mind. The utility of the tandem-repeat approach to resolve the subunit arrangement of an obligate dimer has been demonstrated with LPL and could be generalized for use with other oligomeric enzymes. PMID:9159117

  11. 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

  12. The chemical evolution & physical properties of organic aerosol: A molecular structure based approach

    NASA Astrophysics Data System (ADS)

    Wei, Yiyi; Cao, Tingting; Thompson, Jonathan E.

    2012-12-01

    Global climate, atmospheric chemistry, and air quality are affected by tropospheric particulate matter. Recent measurements suggest organic compounds present in this haze comprise roughly half of total aerosol fine mass concentration globally. Unlike the well-constrained processes which result in formation of nitrate or sulfate aerosol, the oxidation of volatile organics in the atmosphere can lead to thousands of stable compounds in the aerosol phase. Development of a tractable framework to consider the chemical and physical evolution of the organic aerosol is crucial for modeling its effect on global climate. Here we show coupling a 3-dimensional coordinate system defined by the molecular descriptors of molecular weight, heteroatom mass, and double bond equivalents (D.B.E.) with high-resolution molecular mass spectrometry is a powerful approach for describing key properties of the organic aerosol. The scheme is conceptually simple, yet maintains sufficient complexity to be compatible with quantitative structure-property relationships (QSPRs) used to predict chemical and physical properties that govern aerosol behavior. From available data, both ambient organic aerosol and laboratory generated organic aerosol frequently occupy the region characterized by <10 D.B.E. <600 M.W. and <200 heteroatom mass. A QSPR analysis conducted illustrates spatial trends within the 3D space for volatility and Henry's law constants for 31,000 organic compounds considered.

  13. 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

  14. 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.

  15. 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.

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

    PubMed

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

    2013-10-01

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

  17. Diagnosing rejection in renal transplants: a comparison of molecular- and histopathology-based approaches.

    PubMed

    Reeve, J; Einecke, G; Mengel, M; Sis, B; Kayser, N; Kaplan, B; Halloran, P F

    2009-08-01

    The transcriptome has considerable potential for improving biopsy diagnoses. However, to realize this potential the relationship between the molecular phenotype of disease and histopathology must be established. We assessed 186 consecutive clinically indicated kidney transplant biopsies using microarrays, and built a classifier to distinguish rejection from nonrejection using predictive analysis of microarrays (PAM). Most genes selected by PAM were interferon-gamma-inducible or cytotoxic T-cell associated, for example, CXCL9, CXCL11, GBP1 and INDO. We then compared the PAM diagnoses to those from histopathology, which are based on the Banff diagnostic criteria. Disagreement occurred in approximately 20% of diagnoses, principally because of idiosyncratic limitations in the histopathology scoring system. The problematic diagnosis of 'borderline rejection' was resolved by PAM into two distinct classes, rejection and nonrejection. The diagnostic discrepancies between Banff and PAM in these cases were largely due to the Banff system's requirement for a tubulitis threshold in defining rejection. By examining the discrepancies between gene expression and histopathology, we provide external validation of the main features of the histopathology diagnostic criteria (the Banff consensus system), recommend improvements and outline a pathway for introducing molecular measurements.

  18. 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

  19. Predicting biological activity: computational approach using novel distance based molecular descriptors.

    PubMed

    Dutt, R; Madan, A K

    2012-10-01

    Four novel distance based molecular descriptors termed as superpendentic eccentric distance sum indices 1-4 (denoted by:∫P-1EDS, ∫P-2EDS, ∫P-3EDS and ∫P-4EDS) as well as their topochemical counterparts (denoted by:∫cP-1EDS, ∫cP-2EDS, ∫cP-3EDS and ∫cP-4EDS) have been conceptualized and developed in the present study. The sensitivity towards branching, discriminating power, and degeneracy of the proposed novel descriptors were investigated. Utility of these indices was investigated for development of models through decision tree and moving average analysis for the prediction of human corticotropin releasing factor-1 receptor binding affinity of substituted pyrazines. A wide variety of 46 2D and 3D molecular descriptors including proposed indices was employed for development of models through decision tree and moving average analysis. The calculation of most of these descriptors for each compound of the dataset was performed using online E-Dragon software (version 1.0). An in-house computer programme was also employed to calculate additional topological descriptors which did not figure in E-Dragon software. The decision tree classified and correctly predicted the input data with an impressive accuracy of 92% in the training set and 71% during cross-validation. A total of three descriptors, identified by decision tree, were subsequently utilized for development of suitable models using moving average analysis. These models predicted human corticotropin releasing factor-1 receptor binding affinity with an accuracy of ≥85%. The statistical significance of models was assessed through sensitivity, specificity and Matthew's correlation coefficient. High discriminating power, high sensitivity towards branching amalgamated with negligible degeneracy offer proposed descriptors a vast potential for use in the quantitative structure-activity/property/toxicity relationships so as to facilitate drug design.

  20. 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…

  1. Genetic and molecular bases of yield-associated traits: a translational biology approach between rice and wheat.

    PubMed

    Valluru, Ravi; Reynolds, Matthew P; Salse, Jerome

    2014-07-01

    Transferring the knowledge bases between related species may assist in enlarging the yield potential of crop plants. Being cereals, rice and wheat share a high level of gene conservation; however, they differ at metabolic levels as a part of the environmental adaptation resulting in different yield capacities. This review focuses on the current understanding of genetic and molecular regulation of yield-associated traits in both crop species, highlights the similarities and differences and presents the putative knowledge gaps. We focus on the traits associated with phenology, photosynthesis, and assimilate partitioning and lodging resistance; the most important drivers of yield potential. Currently, there are large knowledge gaps in the genetic and molecular control of such major biological processes that can be filled in a translational biology approach in transferring genomics and genetics informations between rice and wheat.

  2. 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

  3. 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)

  4. Molecular features related to HIV integrase inhibition obtained from structure- and ligand-based approaches.

    PubMed

    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 (r(2) = 0.908 and q(2)= 0.643 for 2D model; r(2)= 0.904 and q(2)= 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

  5. Screening and ranking of POPs for global half-life: QSAR approaches for prioritization based on molecular structure.

    PubMed

    Gramatica, Paola; Papa, Ester

    2007-04-15

    Persistence in the environment is an important criterion in prioritizing hazardous chemicals and in identifying new persistent organic pollutants (POPs). Degradation half-life in various compartments is among the more commonly used criteria for studying environmental persistence, but the limited availability of experimental data or reliable estimates is a serious problem. Available half-life data for degradation in air, water, sediment, and soil, for a set of 250 organic POP-type chemicals, were combined in a multivariate approach by principal component analysis to obtain a ranking of the studied organic pollutants according to their relative overall half-life. A global half-life index (GHLI) applicable for POP screening purposes is proposed. The reliability of this index was verified in comparison with multimedia model results. This global index was then modeled as a cumulative end-point using a QSAR approach based on few theoretical molecular descriptors, and a simple and robust regression model externally validated for its predictive ability was derived. The application of this model could allow a fast preliminary identification and prioritization of not yet known POPs, just from the knowledge of their molecular structure. This model can be applied a priori also in the chemical design of safer and alternative non-POP compounds.

  6. Mapping the Druggable Allosteric Space of G-Protein Coupled Receptors: a Fragment-Based Molecular Dynamics Approach

    PubMed Central

    Ivetac, Anthony; Andrew McCammon, J

    2010-01-01

    To address the problem of specificity in G-protein coupled receptor (GPCR) drug discovery, there has been tremendous recent interest in allosteric drugs that bind at sites topographically distinct from the orthosteric site. Unfortunately, structure-based drug design of allosteric GPCR ligands has been frustrated by the paucity of structural data for allosteric binding sites, making a strong case for predictive computational methods. In this work, we map the surfaces of the β1 (β1AR) and β2 (β2AR) adrenergic receptor structures to detect a series of five potentially druggable allosteric sites. We employ the FTMAP algorithm to identify ‘hot spots’ with affinity for a variety of organic probe molecules corresponding to drug fragments. Our work is distinguished by an ensemble-based approach, whereby we map diverse receptor conformations taken from molecular dynamics (MD) simulations totaling approximately 0.5 μs. Our results reveal distinct pockets formed at both solvent-exposed and lipid-exposed cavities, which we interpret in light of experimental data and which may constitute novel targets for GPCR drug discovery. This mapping data can now serve to drive a combination of fragment-based and virtual screening approaches for the discovery of small molecules that bind at these sites and which may offer highly selective therapies. PMID:20626410

  7. 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.

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

    PubMed

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

    2016-05-06

    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.

  9. 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

  10. Cyclodextrin-based molecular machines.

    PubMed

    Hashidzume, Akihito; Yamaguchi, Hiroyasu; Harada, Akira

    2014-01-01

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

  11. 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.

  12. A rapid PCR-based approach for molecular identification of filamentous fungi.

    PubMed

    Chen, Yuanyuan; Prior, Bernard A; Shi, Guiyang; Wang, Zhengxiang

    2011-08-01

    In this study, a novel rapid and efficient DNA extraction method based on alkaline lysis, which can deal with a large number of filamentous fungal isolates in the same batch, was established. The filamentous fungal genomic DNA required only 20 min to prepare and can be directly used as a template for PCR amplification. The amplified internal transcribed spacer regions were easy to identify by analysis. The extracted DNA also can be used to amplify other protein-coding genes for fungal identification. This method can be used for rapid systematic identification of filamentous fungal isolates.

  13. Approaching the alloy limit of thermal conductivity in single-crystalline Si-based thermoelectric nanocomposites: A molecular dynamics investigation

    PubMed Central

    Guo, Ruiqiang; Huang, Baoling

    2015-01-01

    Single-crystalline Si-based nanocomposites have become promising candidates for thermoelectric applications due to their prominent merits. Reducing the thermal conductivity κ without deteriorating the electrical properties is the key to improve their performance. Through non-equilibrium molecular dynamics simulations, we show that κ of single-crystalline Si-based nanocomposites can be reduced to the alloy limit by embedding various nanoinclusions of similar lattice constants but different lattice orientations or space symmetries with respect to the matrix. The surprisingly low κ is mainly due to the large acoustic phonon density of states mismatch caused by the destruction of lattice periodicity at the interfaces between the nanoinclusions and matrix, which leads to the substantial reduction of phonon group velocity and relaxation time, as well as the enhancement of phonon localization. The resulting κ is also temperature-insensitive due to the dominance of boundary scattering. The increase in thermal resistance induced by lattice structure mismatch mainly comes from the nanoinclusions and the channels between them and is caused by the enhanced boundary scattering at the interfaces parallel to the heat flux. Approaching the alloy limit of κ with potentially improved electrical properties by fillers will remarkably improve ZT of single-crystalline Si-based nanocomposites and extend their application. PMID:25851401

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Reactive Intermediates: Molecular and MS-Based Approaches to Assess the Functional Significance of Chemical:Protein Adducts1

    PubMed Central

    Monks, Terrence J.; Lau, Serrine S.

    2014-01-01

    Biologically reactive intermediates formed as endogenous products of various metabolic processes are considered important factors in a variety of human diseases, including Parkinson’s disease and other neurological disorders, diabetes and complications thereof, and other inflammatory-associated diseases. Chemical-induced toxicities are also frequently mediated via the bioactivation of relatively stable organic molecules to reactive electrophilic metabolites. Indeed, chemical-induced toxicities have long been known to be associated with the ability of electrophilic metabolites to react with a variety of targets within the cell, including their covalent adduction to nucleophilic residues in proteins, and nucleotides within DNA. Although we possess considerable knowledge of the various biochemical mechanisms by which chemicals undergo metabolic bioactivation, we understand far less about the processes that couple bioactivation to toxicity. Identifying specific sites within a protein that are targets for adduction can provide the initial information necessary to determine whether such adventitious post-translational modifications significantly alter either protein structure and/or function. To address this problem we have developed MS-based approaches to identify specific amino acid targets of electrophile adduction (electrophile-binding motifs), coupled with molecular modeling of such adducts, to determine the potential structural and functional consequences. Where appropriate, functional assays are subsequently conducted to assess protein function. PMID:23222993

  19. 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.

  20. A modular, energy-based approach to the development of nickel containing molecular electrocatalysts for hydrogen production and oxidation.

    PubMed

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

    2013-01-01

    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 donor abilities and other important thermodynamic parameters. The second coordination sphere includes functional groups such as pendent 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 providing a physical pathway for coupling proton and electron transfer reactions. By controlling both the hydride donor ability of the catalysts using the first coordination sphere and the proton donor abilities of the functional groups in the second coordination sphere, catalysts can be designed that are biased toward H2 production, oxidation, or bidirectional (catalyzing both H2 oxidation and production). The outer coordination sphere is defined as that portion of the catalytic system that is beyond the second coordination sphere. 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 these simple systems provide insights into enzyme function and reactivity that may be difficult to probe in enzymes. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems.

  1. 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.

  2. 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

  3. 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

  4. Assessing the microbiological risk to stored sixteenth century parchment manuscripts: a holistic approach based on molecular and environmental studies.

    PubMed

    Troiano, Federica; Polo, Andrea; Villa, Federica; Cappitelli, Francesca

    2014-01-01

    The microbial risk for the conservation of seven sixteenth century parchment manuscripts, which showed brown discolouration putatively caused by microorganisms, was evaluated using non-invasive sampling techniques, microscopy, studies of surface-associated and airborne microflora with culture-independent molecular methods, and by measuring repository thermo-hygrometric values. Microscopic observations and ATP assays demonstrated a low level of contamination, indicating that the discolouration was not related to currently active microbial colonisation. Nevertheless, a culture-independent molecular approach was adopted to fully characterise surface-associated communities searching for biodeteriogens that could grow under appropriate thermo-hygrometric conditions. Indeed, potential biodeteriogens and microorganisms that are ecologically related to humans were found, suggesting the need to control the conservation environment and improve handling procedures. Microbial loads of air and thermo-hygrometric measurements showed that the repository was not suitable for preventing the microbial deterioration of parchment. A holistic approach to the assessment of risk of microbial deterioration of documents and heritage preservation is proposed for the first time.

  5. Molecular modeling studies on series of Btk inhibitors using docking, structure-based 3D-QSAR and molecular dynamics simulation: a combined approach.

    PubMed

    Balasubramanian, Pavithra K; Balupuri, Anand; Cho, Seung Joo

    2016-03-01

    Bruton tyrosine kinase (Btk) is a non-receptor tyrosine kinase. It is a crucial component in BCR pathway and expressed only in hematopoietic cells except T cells and Natural killer cells. BTK is a promising target because of its involvement in signaling pathways and B cell diseases such as autoimmune disorders and lymphoma. In this work, a combined molecular modeling study of molecular docking, 3D-QSAR and molecular dynamic (MD) simulation were performed on a series of 2,5-diaminopyrimidine compounds as inhibitors targeting Btk kinase to understand the interaction and key residues involved in the inhibition. A structure based CoMFA (q (2) = 0.675, NOC = 5, r (2) = 0.961) and COMSIA (q (2) = 0.704, NOC = 6, r (2) = 0.962) models were developed from the conformation obtained by docking. The developed models were subjected to various validation techniques such as leave-five-out, external test set, bootstrapping, progressive sampling and rm (2) metrics and found to have a good predictive ability in both internal and external validation. Our docking results showed the important residues that interacts in the active site residues in inhibition of Btk kinase. Furthermore, molecular dynamics simulation was employed to study the stability of the docked conformation and to investigate the binding interactions in detail. The MD simulation analyses identified several important hydrogen bonds with Btk, including the gatekeeper residue Thr474 and Met477 at the hinge region. Hydrogen bond with active site residues Leu408 and Arg525 were also recognized. A good correlation between the MD results, docking studies and the contour map analysis are observed. This indicates that the developed models are reliable. Our results from this study can provide insights in the designing and development of more potent Btk kinase inhibitors.

  6. 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)

  7. Molecular approaches to field studies of malaria.

    PubMed

    Beck, Hans-Peter; Tetteh, Kevin

    2008-12-01

    The third 'Molecular Approaches to Malaria' conference was held in Lorne, Australia, in February 2008 and provided extensive information on the application of molecular tools in field studies on malaria. In recent years, technological advances and capacity building in malaria-endemic countries have permitted molecular tools to be applied much more frequently and successfully with exciting new findings. In this review, Hans-Peter Beck and Kevin Tetteh report on the most recent findings using molecular tools in field studies.

  8. 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

  9. Validation of potential inhibitors for SrtA against Bacillus anthracis by combined approach of ligand-based and molecular dynamics simulation.

    PubMed

    Selvaraj, Chandrabose; Singh, Sanjeev Kumar

    2014-01-01

    The development of SrtA inhibitors targeting the biothreat organism namely Bacillus anthracis was achieved by the combined approach of pharmacophore modeling, binding interactions, electron transferring capacity, ADME, and Molecular dynamics studies. In this study, experimentally reported Ba-SrtA inhibitors (pyridazinone and pyrazolethione derivatives) were considered for the development of enhanced pharmacophoric model. The obtained AAAHR hypothesis was a pure theoretical concept that accounts for common molecular interaction network present in experimentally active pyridazinone and pyrazolethione derivatives. Pharmacophore-based screening of AAAHR hypothesis provides several new compounds, and those compounds were treated with four phases of docking protocols with combined Glide-QPLD docking approach. In this approach, scoring and charge accuracy variations were seen to be dominated by QM/MM approach through the allocation of partial charges. Finally, we reported the best compounds from binding db, Chembridge db, and Toslab based on scoring values, energy parameters, electron transfer reaction, ADME, and cell adhesion inhibition activity. The dynamic state of interaction and binding energy assess that new compounds are more active inside the binding pocket and these compounds on experimental validations will survive as better inhibitors for targeting the cell adhesion mechanism of Ba-SrtA. PMID:23869520

  10. Development of a molecular recognition based approach for multi-residue extraction of estrogenic endocrine disruptors from biological fluids coupled to liquid chromatography-tandem mass spectrometry measurement.

    PubMed

    Bousoumah, Radia; Antignac, Jean Philippe; Camel, Valérie; Grimaldi, Marina; Balaguer, Patrick; Courant, Frederique; Bichon, Emmanuelle; Morvan, Marie-Line; Le Bizec, Bruno

    2015-11-01

    Multi-residue methods permitting the high-throughput and affordable simultaneous determination of an extended range of endocrine disrupting chemicals (EDCs) with reduced time and cost of analysis is of prime interest in order to characterize a whole set of bioactive compounds. Such a method based on UHPLC-MS/MS measurement and dedicated to 13 estrogenic EDCs was developed and applied to biological matrices. Two molecular recognition-based strategies, either molecular imprinted polymer (MIP) with phenolic template or estrogen receptors (ERα) immobilized on a sorbent, were assessed in terms of recovery and purification efficiency. Both approaches demonstrated their suitability to measure ultra-trace levels of estrogenic EDCs in aqueous samples. Applicability of the MIP procedure to urine and serum samples has also been demonstrated. PMID:26391401

  11. 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.

  12. 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

  13. 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.

  14. Microbial community analysis of a coastal hot spring in Kagoshima, Japan, using molecular- and culture-based approaches.

    PubMed

    Nishiyama, Minako; Yamamoto, Shuichi; Kurosawa, Norio

    2013-08-01

    Ibusuki hot spring is located on the coastline of Kagoshima Bay, Japan. The hot spring water is characterized by high salinity, high temperature, and neutral pH. The hot spring is covered by the sea during high tide, which leads to severe fluctuations in several environmental variables. A combination of molecular- and culture-based techniques was used to determine the bacterial and archaeal diversity of the hot spring. A total of 48 thermophilic bacterial strains were isolated from two sites (Site 1: 55.6°C; Site 2: 83.1°C) and they were categorized into six groups based on their 16S rRNA gene sequence similarity. Two groups (including 32 isolates) demonstrated low sequence similarity with published species, suggesting that they might represent novel taxa. The 148 clones from the Site 1 bacterial library included 76 operational taxonomy units (OTUs; 97% threshold), while 132 clones from the Site 2 bacterial library included 31 OTUs. Proteobacteria, Bacteroidetes, and Firmicutes were frequently detected in both clone libraries. The clones were related to thermophilic, mesophilic and psychrophilic bacteria. Approximately half of the sequences in bacterial clone libraries shared <92% sequence similarity with their closest sequences in a public database, suggesting that the Ibusuki hot spring may harbor a unique and novel bacterial community. By contrast, 77 clones from the Site 2 archaeal library contained only three OTUs, most of which were affiliated with Thaumarchaeota.

  15. 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.

  16. 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

  17. 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.

  18. An aptameric molecular beacon-based "Signal-on" approach for rapid determination of rHuEPO-alpha.

    PubMed

    Zhang, Zhaoyang; Guo, Lei; Tang, Jijun; Guo, Xingjie; Xie, Jianwei

    2009-12-15

    The aim of this work is to describe the first example of aptameric molecular beacon (MB)-based probe for the detection of recombinant human erythropoietin (rHuEPO-alpha) in physiological buffer, using a novel 35 nt ssDNA aptamer (807-35 nt) originally isolated by Systematic Evolution of Ligands by Exponential enrichment (SELEX) technique in our laboratory. Both "Signal-on" and "Signal-off" MB modes were developed, respectively, in which the conformational alteration of aptamer before and after binding to rHuEPO-alpha can be demonstrated in terms of the correspondingly fluorescent changes. Comparing with "Signal-off" mode, "Signal-on" mode provided higher sensitivity, while with the addition of target rHuEPO-alpha, quenching between fluorescent 807-35 nt aptamer (F-Apt) and a short quencher-labeled complementary sequence (QDNA) was disturbed by the specific binding between rHuEPO-alpha and F-Apt. QDNA was thus loosened and released from F-Apt, leading to a consequently full fluorescent restoration. Systematic optimization of parameters in "Signal-on" mode were carried out, the choice of QDNA length, the hybridization site of a small supplementary DNA (SDNA) stabilizer, and the existence of Mg(2+) cation played essential roles for the performance characterization. A convenient and sensitive determination of rHuEPO-alpha with a LOD of 0.4 nM was achieved.

  19. 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.

  20. Huntington Disease: Molecular Diagnostics Approach.

    PubMed

    Bastepe, Murat; Xin, Winnie

    2015-10-06

    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.

  1. An approach to molecular composites

    NASA Astrophysics Data System (ADS)

    Krigbaum, W. R.; Preston, J.

    1982-12-01

    One objective was to demonstrate that a nematogen can be made to exhibit a cholesteric phase by the incorporation of chiral centers into the polymer chain. The Yamazaki reaction was used to introduce 3 mole percent of chiral L-valine into poly(p-benzamide). This was shown to form a lyotropic cholesteric phase by circular dichroism and the induced circular dichroism of an achiral dye. A disadvantage of the use of lyotropic mesomorphism was that few solvents were available and the production costs were high. The early lattice model treatment of Flory indicated that a highly extended molecular conformation was essential to the formation of this type of mesophase. It has been demonstrated that the melting point depression of a crystalline polymer by this type of mesophase will be quite small unless the polymer-solvent interaction is very favorable. This implies that the polymer solubility will only be sufficient for the formation of a lyotropic mesaphase for those few polymer-solvent systems in which the interactions were very favorable. It was found that the Yamazaki phosphorylation reaction could be made to yield aromatic polyamides of higher inherent viscosity by using a monomer having pre-formed amide linkages. It is believed that this occurs due to reduction in the byproducts of the polymerization.

  2. 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...

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

    PubMed

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

    2014-10-28

    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.

  8. 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.

  9. 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

  10. Network Based Approach in the Establishment of the Relationship between Type 2 Diabetes Mellitus and Its Complications at the Molecular Level Coupled with Molecular Docking Mechanism

    PubMed Central

    Rampogu Lemuel, Mary

    2016-01-01

    Diabetes mellitus (DM) is one of the major metabolic disorders that is currently threatening the world. DM is seen associated with obesity and diabetic retinopathy (DR). In the present paper we tried to evaluate the relationship between the three aliments at the gene level and further performed the molecular docking to identify the common drug for all the three diseases. We have adopted several software programs such as Phenopedia, VennViewer, and CDOCKER to accomplish the objective. Our results revealed six genes that commonly associated and are involved in the signalling pathway. Furthermore, evaluation of common gene association from the selected set of genes projected the presence of SIRT1 in all the three aliments. Therefore, we targeted protein 4KXQ which was produced from the gene SIRT1 and challenged it with eight phytochemicals, adopting the CDOCKER. C1 compound has displayed highest -CDOCKER energy and -CDOCKER interaction energy of 43.6905 and 43.3953, respectively. Therefore, this compound is regarded as the most potential lead molecule.

  11. Network Based Approach in the Establishment of the Relationship between Type 2 Diabetes Mellitus and Its Complications at the Molecular Level Coupled with Molecular Docking Mechanism

    PubMed Central

    Rampogu Lemuel, Mary

    2016-01-01

    Diabetes mellitus (DM) is one of the major metabolic disorders that is currently threatening the world. DM is seen associated with obesity and diabetic retinopathy (DR). In the present paper we tried to evaluate the relationship between the three aliments at the gene level and further performed the molecular docking to identify the common drug for all the three diseases. We have adopted several software programs such as Phenopedia, VennViewer, and CDOCKER to accomplish the objective. Our results revealed six genes that commonly associated and are involved in the signalling pathway. Furthermore, evaluation of common gene association from the selected set of genes projected the presence of SIRT1 in all the three aliments. Therefore, we targeted protein 4KXQ which was produced from the gene SIRT1 and challenged it with eight phytochemicals, adopting the CDOCKER. C1 compound has displayed highest -CDOCKER energy and -CDOCKER interaction energy of 43.6905 and 43.3953, respectively. Therefore, this compound is regarded as the most potential lead molecule. PMID:27699170

  12. An artificial intelligence approach for modeling molecular self-assembly: agent-based simulations of rigid molecules.

    PubMed

    Fortuna, Sara; Troisi, Alessandro

    2009-07-23

    Agent-based simulations are rule-based models traditionally used for the simulations of complex systems. In this paper, an algorithm based on the concept of agent-based simulations is developed to predict the lowest energy packing of a set of identical rigid molecules. The agents are identified with rigid portions of the system under investigation, and they evolve following a set of rules designed to drive the system toward the lowest energy minimum. The algorithm is compared with a conventional Metropolis Monte Carlo algorithm, and it is applied on a large set of representative models of molecules. For all the systems studied, the agent-based method consistently finds a significantly lower energy minima than the Monte Carlo algorithm because the system evolution includes elements of adaptation (new configurations induce new types of moves) and learning (past successful choices are repeated).

  13. 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

  14. Approaches to airborne molecular contamination assessment

    NASA Astrophysics Data System (ADS)

    Riddle Vogt, Sarah; Landoni, Cristian

    2011-03-01

    Airborne molecular contamination (AMC) assessment approaches can vary greatly between different fabs and even between different divisions within a given company. Some companies have very rigorous testing schedules (such as those needed to maintain tool warranties) while others feel AMC testing is only necessary when they are having a problem. While choosing to only test for AMC when a trouble arises may be cost effective in the short term it can have significant impacts on tools, in particular tool optics, and product losses due to defects which can cost significantly more in the long term than the AMC testing would have. Another critical issue in assessing AMC is what species you should be testing for. Some volatile species may not cause an issue in your process while part-per-trillion volume (pptv) amounts of others can do serious damage to your tools and/or products. Knowledge of which volatile compounds can cause problems in your applications and at what levels is crucial in deciding what type of AMC assessment to perform and at what frequency. Typically four classes of AMC are routinely monitored in clean rooms and tool environments: acids, bases, hydrocarbons, and refractory compounds. Real world examples will be presented using the solely solid-state trap collection methods utilized by SAES Pure Gas.

  15. Combining Select Neuropsychological Assessment With Blood-Based Biomarkers to detect Mild Alzheimer’s disease: A Molecular Neuropsychology approach

    PubMed Central

    Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O’Bryant, Sid

    2015-01-01

    Background The current project sought to create combined biomarker-cognitive profile to detect mild Alzheimer’s disease. Methods Data was analyzed from 266 participants (129 AD cases [Early AD n=93; Very Early AD n=36]; 137 controls) enrolled in the Texas Alzheimer’s Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochmiluminescence (ECL). Logistic Regression was utilized to detect early AD using two serum biomarkers (TNFα and IL7), demographic information (age) and one neuropsychological measure (Clock-4 point) as predictor variable. Disease severity was determined via Clinical Dementia Rating scale global scores. Results In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90 and an overall accuracy of 0.92. When examining early AD cases (i.e. CDR=0.5-1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85 and an overall accuracy of 0.91. When restricted to very early AD cases (i.e CDR=0.5), the biomarker-cognitive profile yielded SN of 0.97, SP of 0.72 with an overall accuracy of 0.91. Conclusions The combination of demographics + 2 biomarkers + 1 cognitive test created a biomarker-cognitive profile that was highly accurate in detecting AD presence, even in the very early stages. This work demonstrates the complementary nature of each modality (blood biomarkers + neuropsychological assessment) and supports our previously proposed concept for Molecular Neuropsychology. PMID:24916542

  16. 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.

  17. 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…

  18. 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.

  19. 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

  20. Molecular approaches in the diagnosis of dermatophytosis.

    PubMed

    Kanbe, Toshio

    2008-01-01

    Dermatophytosis is one of the most common infectious diseases in the world and can be caused by several dermatophyte species. These species are closely related in genetic structure in spite of different phenotypic and ecological features. The morphological similarity, variability, and polymorphism of dermatophytes have meant that species identification for dermatophytes is time consuming and requires a significant degree of knowledge and technological expertise. Molecular biology-based techniques have solved problems concerning the morphology-based identification of dermatophytes and have improved our knowledge on the epidemiology of dermatophytosis. Further development of molecular diagnosis of dermatophytosis requires the investigation of additional molecular markers for diagnostic tools targeting multiple loci as well as the improvement of techniques.

  1. 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

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

    PubMed

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

    2016-02-01

    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.

  3. 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.

  4. 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).

  5. 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

  6. 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

  7. Molecular biology approaches in bioadhesion research

    PubMed Central

    Rodrigues, Marcelo; Lengerer, Birgit; Ostermann, Thomas

    2014-01-01

    Summary The use of molecular biology tools in the field of bioadhesion is still in its infancy. For new research groups who are considering taking a molecular approach, the techniques presented here are essential to unravelling the sequence of a gene, its expression and its biological function. Here we provide an outline for addressing adhesion-related genes in diverse organisms. We show how to gradually narrow down the number of candidate transcripts that are involved in adhesion by (1) generating a transcriptome and a differentially expressed cDNA list enriched for adhesion-related transcripts, (2) setting up a BLAST search facility, (3) perform an in situ hybridization screen, and (4) functional analyses of selected genes by using RNA interference knock-down. Furthermore, latest developments in genome-editing are presented as new tools to study gene function. By using this iterative multi-technologies approach, the identification, isolation, expression and function of adhesion-related genes can be studied in most organisms. These tools will improve our understanding of the diversity of molecules used for adhesion in different organisms and these findings will help to develop innovative bio-inspired adhesives. PMID:25161834

  8. 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

  9. 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

  10. Performance of plane-wave-based LDA+U and GGA+U approaches to describe magnetic coupling in molecular systems.

    PubMed

    Rivero, Pablo; Loschen, Christoph; Moreira, Ibério De P R; Illas, Francesc

    2009-11-15

    This work explores the performance of periodic plane wave density functional theory calculations with an on-site Coulomb correction to the standard LDA and GGA exchange-correlation potential--commonly used to describe strongly correlated solids--in describing the magnetic coupling constant of a series of molecular compounds representative of dinuclear Cu complexes and of organic diradicals. The resulting LDA+U or GGA+U formalisms, lead to results comparable to experiment and to those obtained by means of standard hybrid functionals provided that the value of the U parameter is adequately chosen. Hence, these methods offer an alternative efficient computational scheme to correct LDA and GGA approaches to adequately describe the electronic structure and magnetic coupling in large molecular magnetic systems, although at the expenses of introducing an empirical (U) parameter. For all investigated copper dinuclear systems, the LDA+U and GGA+U approaches lead to an improvement in the description of magnetic properties over the original LDA and GGA schemes with an accuracy similar to that arising from the hybrid B3LYP functional, by increasing the on-site Coulomb repulsion with a moderate U value. Nevertheless, the introduction of an arbitrary U value in the 0-10 eV range most often provides the correct ground-state spin distribution and the correct sign of the magnetic coupling constant.

  11. 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.

  12. Hydantoin-based molecular photoswitches.

    PubMed

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

    2015-04-17

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

  13. 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.

  14. Integrating docking and molecular dynamics approaches for a series of proline-based 2,5-diketopiperazines as novel αβ-tubulin inhibitors.

    PubMed

    Fani, Najmeh; Bordbar, Abdol-Khalegh; Ghayeb, Yousef; Sepehri, Saghi

    2015-01-01

    In this work, docking tools were utilized in order to study the binding properties of more than five hundred of proline-based 2,5-diketopiperazine in the binding site of αβ-tubulin. Results revealed that 20 compounds among them showed lower binding energies in comparison with Tryprostatin-A, a well known tubulin inhibitor and therefore could be potential inhibitors of tubulin. However, the precise evaluation of binding poses represents the similar binding modes for all of these compounds and Tryprostatin-A. Finally, the best docked complex was subjected to a 25 ns molecular dynamics simulation to further validate the proposed binding mode of this compound.

  15. 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

  16. 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.

  17. Molecular approaches to differentiate three species of Nematodirus in sheep and goats from China based on internal transcribed spacer rDNA sequences.

    PubMed

    Zhao, G H; Jia, Y Q; Bian, Q Q; Nisbet, A J; Cheng, W Y; Liu, Y; Fang, Y Q; Ma, X T; Yu, S K

    2015-05-01

    Internal transcribed spacer (ITS) rDNA sequences of three Nematodirus species from naturally infected goats or sheep in two endemic provinces of China were analysed to establish an effective molecular approach to differentiate Nematodirus species in small ruminants. The respective intra-specific genetic variations in ITS1 and ITS2 rDNA regions were 0.3-1.8% and 0-0.4% in N. spathiger, 0-6.5% and 0-5.4% in N. helvetianus, and 0-4.4% and 0-6.1% in N. oiratianus from China. The respective intra-specific variations of ITS1 and ITS2 were 1.8-4.4% and 1.6-6.1% between N. oiratianus isolates from China and Iran, 5.7-7.1% and 6.3-8.3% between N. helvetianus samples from China and America. For N. spathiger, compared with samples from China, sequence differences in ITS1 rDNA were 0.3-2.4% in isolates from America, 0.3-2.9% in New Zealand and 2.1-2.4% in Australia. Genetic variations in ITS2 rDNA of N. spathiger were 0-0.4% between samples from China and America, and 0-0.8% between samples from China and New Zealand. Using mutation sites, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and specific PCR techniques were developed to differentiate these three Nematodirus species. The specific PCR assay allowed the accurate identification of N. oiratianus from other common nematodes with a sensitivity of 0.69 pg and further examination of Nematodirus samples demonstrated the reliability of these two molecular methods.

  18. 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.

  19. Identification of dual Acetyl-CoA carboxylases 1 and 2 inhibitors by pharmacophore based virtual screening and molecular docking approach.

    PubMed

    Bhadauriya, Anuseema; Dhoke, Gaurao V; Gangwal, Rahul P; Damre, Mangesh V; Sangamwar, Abhay T

    2013-02-01

    Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme that plays a vital role in obesity-induced type 2 diabetes and fatty acid metabolism. To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed. The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features. The best pharmacophore hypotheses were validated by various methods such as test set, decoy set and Cat-Scramble methodology. The validated pharmacophore models were used to screen several small-molecule databases, including Specs, NCI, ChemDiv and Natural product databases to identify the potential dual ACC inhibitors. The virtual hits were then subjected to several filters such as estimated [Formula: see text] value, quantitative estimation of drug-likeness and molecular docking analysis. Finally, three novel compounds with diverse scaffolds were selected as potential starting points for the design of novel dual ACC inhibitors.

  20. 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

  1. Insight into the Structural Requirements of Theophylline-Based Aldehyde Dehydrogenase lAl (ALDHlAl) Inhibitors Through Multi-QSAR Modeling and Molecular Docking Approaches.

    PubMed

    Abdul Amin, Sk; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

    2016-01-01

    Over expression of aldehyde dehydrogenase (ALDH1A1) is one of the vital hallmarks of the self-renewal and differentiational cancer stem cells (CSCs). Till now, no selective ALDH1A1 inhibitor is commercially available in the market. So there is an urgent need to explore some novel molecules which can selectively inhibit ALDH1A1 to combat cancer. Presently, our work deals with the development of QSAR models of some theophylline-based molecules by conventional 2D-QSAR, hologram QSAR (HQSAR), and Bayesian classification modeling. The descriptors identified from these QSAR models give avenues to modulate the structure of theophylline-based compounds to a desirable biological end point. Molecular docking study reveals the selectivity of these molecules towards ALDH1A1 (PDB: 4WP7) and important binding residues (GLY 125, 458; THR 129; TRP 178; TYR 297; PHE 171, 466; VAL 174, 460; MET 175; HIS 293 etc.) for the interaction with the receptors. The current study may help to design novel compounds as selective ALDH1A1 inhibitors. PMID:27132720

  2. Highly sensitive DNA detection and point mutation identification: an electrochemical approach based on the combined use of ligase and reverse molecular beacon.

    PubMed

    Wu, Zai-Sheng; Jiang, Jian-Hui; Shen, Guo-Li; Yu, Ru-Qin

    2007-06-01

    A novel strategy is described for highly sensitive DNA detection and point mutation identification based on the combination of reverse molecular beacon with DNA ligase. A 5'-phosphoryl and 3'-ferrocene terminated DNA sequence is used as detection probe, which may be ligated to capture DNA immobilized on an electrode surface in the presence of a target DNA strand that is complementary to the ends of each DNA, since this allows formation of a nicked, double-stranded DNA. The ligation product may form a hairpin structure after the removal of target DNA. By this method, target DNA can be determined in the range from 3.4 x 10(-12) to 1.4 x 10(-7) M with a detection limit of 1.0 x 10(-12) M. In contrast to existing methods based on the conformation change of redox-labeled oligonucleotides, the proposed strategy offers several substantial advantages: first, the background peak current is eliminated as the ferrocene (Fc)-tagged oligonucleotide probe is specifically ligated to capture DNA; second, a "signal-on" mechanism makes the current intensity increase with increasing target DNA concentration; third, improved current signal is obtained due to the formation of the hairpin structure of ligation products. Additionally, the present system exhibits excellent capability to discriminate mutant target sequences from fully complementary target sequences.

  3. Imaging approaches to optimize molecular therapies.

    PubMed

    Weissleder, Ralph; Schwaiger, Markus C; Gambhir, Sanjiv Sam; Hricak, Hedvig

    2016-09-01

    Imaging, including its use for innovative tissue sampling, is slowly being recognized as playing a pivotal role in drug development, clinical trial design, and more effective delivery and monitoring of molecular therapies. The challenge is that, while a considerable number of new imaging technologies and new targeted tracers have been developed for cancer imaging in recent years, the technologies are neither evenly distributed nor evenly implemented. Furthermore, many imaging innovations are not validated and are not ready for widespread use in drug development or in clinical trial designs. Inconsistent and often erroneous use of terminology related to quantitative imaging biomarkers has also played a role in slowing their development and implementation. We examine opportunities for, and challenges of, the use of imaging biomarkers to facilitate development of molecular therapies and to accelerate progress in clinical trial design. In the future, in vivo molecular imaging, image-guided tissue sampling for mutational analyses ("high-content biopsies"), and noninvasive in vitro tests ("liquid biopsies") will likely be used in various combinations to provide the best possible monitoring and individualized treatment plans for cancer patients. PMID:27605550

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

    PubMed

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

    2007-01-01

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

  5. 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

  6. Interference-based molecular transistors

    PubMed Central

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

    2016-01-01

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

  7. Interference-based molecular transistors.

    PubMed

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

    2016-01-01

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

  8. Thermal force approach to molecular evolution.

    PubMed

    Braun, Dieter; Libchaber, Albert

    2004-06-01

    Recent experiments are discussed where temperature gradients across mesoscopic pores are shown to provide essential mechanisms for autonomous molecular evolution. On the one hand, laminar thermal convection can drive DNA replication as the molecules are continuously cycled between hot and cold regions of a chamber. On the other hand, thermophoresis can accumulate charged biopolymers in similar convection settings. The experiments show that temperature differences analogous to those across porous rocks present a robust nonequilibrium boundary condition to feed the replication and accumulation of evolving molecules. It is speculated that similar nonequilibrium conditions near porous submarine hydrothermal mounds could have triggered the origin of life. In such a scenario, the encapsulation of cells with membranes would be a later development. It is expected that detailed studies of mesoscopic boundary conditions under nonequilibrium conditions will reveal new connecting pieces in the fascinating puzzle of the origins of life. PMID:16204812

  9. [Molecular bases of prion diseases].

    PubMed

    Pokrovskiĭ, V I; Kiselev, O I

    1998-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Fusarium diversity in soil using a specific molecular approach and a cultural approach.

    PubMed

    Edel-Hermann, Véronique; Gautheron, Nadine; Mounier, Arnaud; Steinberg, Christian

    2015-04-01

    Fusarium species are ubiquitous in soil. They cause plant and human diseases and can produce mycotoxins. Surveys of Fusarium species diversity in environmental samples usually rely on laborious culture-based methods. In the present study, we have developed a molecular method to analyze Fusarium diversity directly from soil DNA. We designed primers targeting the translation elongation factor 1-alpha (EF-1α) gene and demonstrated their specificity toward Fusarium using a large collection of fungi. We used the specific primers to construct a clone library from three contrasting soils. Sequence analysis confirmed the specificity of the assay, with 750 clones identified as Fusarium and distributed among eight species or species complexes. The Fusarium oxysporum species complex (FOSC) was the most abundant one in the three soils, followed by the Fusarium solani species complex (FSSC). We then compared our molecular approach results with those obtained by isolating Fusarium colonies on two culture media and identifying species by sequencing part of the EF-1α gene. The 750 isolates were distributed into eight species or species complexes, with the same dominant species as with the cloning method. Sequence diversity was much higher in the clone library than in the isolate collection. The molecular approach proved to be a valuable tool to assess Fusarium diversity in environmental samples. Combined with high throughput sequencing, it will allow for in-depth analysis of large numbers of samples.

  12. Fusarium diversity in soil using a specific molecular approach and a cultural approach.

    PubMed

    Edel-Hermann, Véronique; Gautheron, Nadine; Mounier, Arnaud; Steinberg, Christian

    2015-04-01

    Fusarium species are ubiquitous in soil. They cause plant and human diseases and can produce mycotoxins. Surveys of Fusarium species diversity in environmental samples usually rely on laborious culture-based methods. In the present study, we have developed a molecular method to analyze Fusarium diversity directly from soil DNA. We designed primers targeting the translation elongation factor 1-alpha (EF-1α) gene and demonstrated their specificity toward Fusarium using a large collection of fungi. We used the specific primers to construct a clone library from three contrasting soils. Sequence analysis confirmed the specificity of the assay, with 750 clones identified as Fusarium and distributed among eight species or species complexes. The Fusarium oxysporum species complex (FOSC) was the most abundant one in the three soils, followed by the Fusarium solani species complex (FSSC). We then compared our molecular approach results with those obtained by isolating Fusarium colonies on two culture media and identifying species by sequencing part of the EF-1α gene. The 750 isolates were distributed into eight species or species complexes, with the same dominant species as with the cloning method. Sequence diversity was much higher in the clone library than in the isolate collection. The molecular approach proved to be a valuable tool to assess Fusarium diversity in environmental samples. Combined with high throughput sequencing, it will allow for in-depth analysis of large numbers of samples. PMID:25655778

  13. 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.

  14. Molecular approach to allergy diagnosis and therapy.

    PubMed

    Ferreira, Fatima; Wolf, Martin; Wallner, Michael

    2014-07-01

    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.

  15. 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

  16. 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.

  17. 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.

  18. Density based visualization for molecular simulation.

    PubMed

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

    2014-01-01

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

  19. 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.

  20. 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.

  1. 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.

  2. 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

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

    PubMed

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

    2016-09-20

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

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

    PubMed

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

    2016-09-20

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

  5. 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.

  6. 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

  7. Molecular bulk heterojunctions: an emerging approach to organic solar cells.

    PubMed

    Roncali, Jean

    2009-11-17

    The predicted exhaustion of fossil energy resources and the pressure of environmental constraints are stimulating an intensification of research on renewable energy sources, in particular, on the photovoltaic conversion of solar energy. In this context, organic solar cells are attracting increasing interest that is motivated by the possibility of fabricating large-area, lightweight, and flexible devices using simple techniques with low environmental impact. Organic solar cells are based on a heterojunction resulting from the contact of a donor (D) and an acceptor (A) material. Absorption of solar photons creates excitons, Coulombically bound electron-hole pairs, which diffuse to the D/A interface, where they are dissociated into free holes and electrons by the electric field. D/A heterojunctions can be created with two types of architectures, namely, bilayer heterojunction and bulk heterojunction (BHJ) solar cells. BHJ cells combine the advantages of easier fabrication and higher conversion efficiency due to the considerably extended D/A interface. Until now, the development of BHJ solar cells has been essentially based on the use of soluble pi-conjugated polymers as donor material. Intensive interdisciplinary research carried out in the past 10 years has led to an increase in the conversion efficiency of BHJ cells from 0.10 to more than 5.0%. These investigations have progressively established regioregular poly(3-hexylthiophene) (P3HT) as the standard donor material for BHJ solar cells, owing to a useful combination of optical and charge-transport properties. However, besides the limit imposed to the maximum conversion efficiency by its intrinsic electronic properties, P3HT and more generally polymers pose several problems related to the control of their structure, molecular weight, polydispersity, and purification. In this context, recent years have seen the emergence of an alternative approach based on the replacement of polydisperse polymers by soluble

  8. Molecular bulk heterojunctions: an emerging approach to organic solar cells.

    PubMed

    Roncali, Jean

    2009-11-17

    The predicted exhaustion of fossil energy resources and the pressure of environmental constraints are stimulating an intensification of research on renewable energy sources, in particular, on the photovoltaic conversion of solar energy. In this context, organic solar cells are attracting increasing interest that is motivated by the possibility of fabricating large-area, lightweight, and flexible devices using simple techniques with low environmental impact. Organic solar cells are based on a heterojunction resulting from the contact of a donor (D) and an acceptor (A) material. Absorption of solar photons creates excitons, Coulombically bound electron-hole pairs, which diffuse to the D/A interface, where they are dissociated into free holes and electrons by the electric field. D/A heterojunctions can be created with two types of architectures, namely, bilayer heterojunction and bulk heterojunction (BHJ) solar cells. BHJ cells combine the advantages of easier fabrication and higher conversion efficiency due to the considerably extended D/A interface. Until now, the development of BHJ solar cells has been essentially based on the use of soluble pi-conjugated polymers as donor material. Intensive interdisciplinary research carried out in the past 10 years has led to an increase in the conversion efficiency of BHJ cells from 0.10 to more than 5.0%. These investigations have progressively established regioregular poly(3-hexylthiophene) (P3HT) as the standard donor material for BHJ solar cells, owing to a useful combination of optical and charge-transport properties. However, besides the limit imposed to the maximum conversion efficiency by its intrinsic electronic properties, P3HT and more generally polymers pose several problems related to the control of their structure, molecular weight, polydispersity, and purification. In this context, recent years have seen the emergence of an alternative approach based on the replacement of polydisperse polymers by soluble

  9. Visual-size molecular recognition based on gels.

    PubMed

    Tu, Tao; Fang, Weiwei; Sun, Zheming

    2013-10-01

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

  10. 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.

  11. Prospecting Environmental Mycobacteria: Combined Molecular Approaches Reveal Unprecedented Diversity

    PubMed Central

    Pontiroli, Alessandra; Khera, Tanya T.; Oakley, Brian B.; Mason, Sam; Dowd, Scot E.; Travis, Emma R.; Erenso, Girum; Aseffa, Abraham; Courtenay, Orin; Wellington, Elizabeth M. H.

    2013-01-01

    Background Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in

  12. Molecular bases of protein halotolerance.

    PubMed

    Graziano, Giuseppe; Merlino, Antonello

    2014-04-01

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

  13. Carboplatin versus cisplatin: density functional approach to their molecular properties

    NASA Astrophysics Data System (ADS)

    Tornaghi, Elena; Andreoni, Wanda; Carloni, Paolo; Hutter, Jürg; Parrinello, Michele

    1995-12-01

    Carboplatin is a platinum-based drug in common clinical use. Here we present the first ab initio calculation of its molecular properties, namely structural, electronic and vibrational. Comparison of the calculated molecular structure with experimental data taken in the solid phase shows quite good agreement. Comparison of our results on its parent complex, cisplatin, is particularly instructive. Unlike the chlorine ligands in cisplatin, the substituting dicarboxylate strongly participates in the chemically active orbitals.

  14. 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...

  15. Carbon-based ion and molecular channels

    NASA Astrophysics Data System (ADS)

    Sint, Kyaw; Wang, Boyang; Kral, Petr

    2008-03-01

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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Molecularly guided therapy of neuroblastoma: a review of different approaches.

    PubMed

    Tonini, Gian Paolo; Pistoia, Vito

    2006-01-01

    Neuroblastoma (NB) is the most frequent extra-cranial solid tumor and the first cause of lethality in pre-school age children. NB accounts for 9-10% of pediatric tumors and affects more than ten thousand children a year. It originates from the sympathetic nervous system and is characterized by heterogeneous pathological and clinical presentation. Stage 4 NB represents approximately 50% of the cases and shows metastatic dissemination at onset; its prognosis is grim, with 20% of the patients surviving at 5 years from diagnosis in spite of aggressive chemotherapy with autologous hematopoietic stem cell support. Novel therapeutic strategies are urgently needed to improve the prognosis of stage 4 NB patients. Here we review the most promising approaches to NB treatment that have already reached clinical testing or have proved to be successful in preclinical models of the disease. All of these approaches are molecularly guided, since their rational development has benefited from the enormous amount of information on the biology of neuroblastoma gathered through molecular biology and genetics studies. The following topics are reviewed: MYCN oncogene amplification as parameter for therapeutic decision, minimal residual disease, immunotherapy, gene therapy, differentiation and apoptotic therapy, anti-angiogenic therapy, gene expression profiling as tool for generating novel therapeutic approaches. Although several efforts are still needed to reach a significant cure of patients with neuroblastoma, molecularly guided approaches have opened new ways to neuroblastoma treatment and can represent useful models for other cancers of either childhood or adulthood.

  3. Bioassays Based on Molecular Nanomechanics

    PubMed Central

    Majumdar, Arun

    2002-01-01

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

  4. Bioassays Based on Molecular Nanomechanics

    DOE PAGES

    Majumdar, Arun

    2002-01-01

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

  5. 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.

  6. 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.

  7. Molecular and genetic bases of pancreatic cancer.

    PubMed

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

    2012-06-01

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

  8. Modeling and simulation of molecular biology systems using petri nets: modeling goals of various approaches.

    PubMed

    Hardy, Simon; Robillard, Pierre N

    2004-12-01

    Petri nets are a discrete event simulation approach developed for system representation, in particular for their concurrency and synchronization properties. Various extensions to the original theory of Petri nets have been used for modeling molecular biology systems and metabolic networks. These extensions are stochastic, colored, hybrid and functional. This paper carries out an initial review of the various modeling approaches based on Petri net found in the literature, and of the biological systems that have been successfully modeled with these approaches. Moreover, the modeling goals and possibilities of qualitative analysis and system simulation of each approach are discussed.

  9. 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

  10. 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

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

    PubMed

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

    2016-06-16

    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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Molecular interactions and crystal packing in nematogen: Computational thermodynamic approach

    NASA Astrophysics Data System (ADS)

    Lakshmi Praveen, P.; Ojha, Durga P.

    2011-10-01

    A computational thermodynamic approach of molecular interactions in a nematogen p-n-alkyl benzoic acid ( nBAC) molecule with an alkyl group butyl (4BAC) has been carried out with respect to translational and orientational motion. The atomic net charge and dipole moment at each atomic center were evaluated using the complete neglect differential overlap (CNDO/2) method. The modified Rayleigh-Schrödinger perturbation theory along with multicentered-multipole expansion method were employed to evaluate long-range intermolecular interactions, while a 6-exp potential function was assumed for short-range interactions. Various possible geometrical arrangements of molecular pairs with regard to different energy components were considered, and the energetically favorable configuration was found to understand the crystal packing picture. Furthermore, these interaction energy values are taken as input to calculate the configurational entropy at room temperature (300 K), nematic-isotropic transition temperature (386 K) and above transition temperature (450 K) during different modes of interactions. An attempt has been made to describe interactions in a nematogen at molecular level, through which one can simplify the system to make the model computationally feasible in understanding the delicate interplay between energy and entropy, that accounts for mesomorphism and there by to analyze the molecular structure of a nematogen.

  17. Molecular beacons: a new approach to plant virus detection.

    PubMed

    Eun, A J; Wong, S M

    2000-03-01

    ABSTRACT Molecular beacons are single-stranded nucleic acid molecules with a stem-loop conformation. The stem portion consists of complementary sequences at the 5' and 3' terminals of the molecule, while the loop portion consists of probe sequences that are complementary to the target sequences of choice. A fluorescent moiety is attached to one end, while a quenching moiety is attached to the opposite end. Reverse transcription-polymerase chain reactions are carried out with primers that amplify specific genome sequences of interest, yielding targets complementary to their respective molecular beacons for subsequent detection. Here, we have designed four molecular beacons specific to the RNA-dependent RNA polymerase and coat protein genes of two orchid viruses, namely Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV). This technology is successfully applied to detect as little as 0.5 ng of viral RNA of both orchid viruses simultaneously in 100 mg of coinfected Oncidium orchid leaves. This rapid and specific technique is applicable to the orchid industry, which routinely carries out virus indexing and screening for virus-resistant cultivars. We belief that use of this molecular beacon approach can be extended to the detection of multiple plant viruses in various crops.

  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. 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.

  20. [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.

  1. [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

  2. Transport in molecular states language: Generalized quantum master equation approach

    NASA Astrophysics Data System (ADS)

    Esposito, Massimiliano; Galperin, Michael

    2009-05-01

    A simple scheme, capable of treating transport in molecular junctions in the language of many-body states, is presented. By introducing an ansatz in Liouville space, similar to the generalized Kadanoff-Baym approximation, a quantum master equation (QME)-like expression is derived starting from the exact equation of motion for Hubbard operators. Using an effective Liouville space propagation, a dressing similar to the standard diagrammatic one is proposed. The scheme is compared to the standard QME approach and its applicability to transport calculations is discussed.

  3. Multiple virtual screening approaches for finding new Hepatitis c virus RNA-dependent RNA polymerase inhibitors: Structure-based screens and molecular dynamics for the pursue of new poly pharmacological inhibitors

    PubMed Central

    2012-01-01

    The RNA polymerase NS5B of Hepatitis C virus (HCV) is a well-characterised drug target with an active site and four allosteric binding sites. This work presents a workflow for virtual screening and its application to Drug Bank screening targeting the Hepatitis C Virus (HCV) RNA polymerase non-nucleoside binding sites. Potential polypharmacological drugs are sought with predicted active inhibition on viral replication, and with proven positive pharmaco-clinical profiles. The approach adopted was receptor-based. Docking screens, guided with contact pharmacophores and neural-network activity prediction models on all allosteric binding sites and MD simulations, constituted our analysis workflow for identification of potential hits. Steps included: 1) using a two-phase docking screen with Surflex and Glide Xp. 2) Ranking based on scores, and important H interactions. 3) a machine-learning target-trained artificial neural network PIC prediction model used for ranking. This provided a better correlation of IC50 values of the training sets for each site with different docking scores and sub-scores. 4) interaction pharmacophores-through retrospective analysis of protein-inhibitor complex X-ray structures for the interaction pharmacophore (common interaction modes) of inhibitors for the five non-nucleoside binding sites were constructed. These were used for filtering the hits according to the critical binding feature of formerly reported inhibitors. This filtration process resulted in identification of potential new inhibitors as well as formerly reported ones for the thumb II and Palm I sites (HCV-81) NS5B binding sites. Eventually molecular dynamics simulations were carried out, confirming the binding hypothesis and resulting in 4 hits. PMID:23282180

  4. Challenges and novel approaches for investigating molecular mediation

    PubMed Central

    Richmond, R.C.; Hemani, G.; Tilling, K.; Davey Smith, G.; Relton, C.L.

    2016-01-01

    Understanding mediation is useful for identifying intermediates lying between an exposure and an outcome which, when intervened upon, will block (some or all of) the causal pathway between the exposure and outcome. Mediation approaches used in conventional epidemiology have been adapted to understanding the role of molecular intermediates in situations of high-dimensional omics data with varying degrees of success. In particular, the limitations of observational epidemiological study including confounding, reverse causation and measurement error can afflict conventional mediation approaches and may lead to incorrect conclusions regarding causal effects. Solutions to analysing mediation which overcome these problems include the use of instrumental variable methods such as Mendelian randomization, which may be applied to evaluate causality in increasingly complex networks of omics data. PMID:27439390

  5. 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.

  6. 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

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

    PubMed

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

    2015-07-22

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

  8. 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.

  9. Molecular/cell engineering approach to autocrine ligand control of cell function.

    PubMed

    Lauffenburger, D A; Forsten, K E; Will, B; Wiley, H S

    1995-01-01

    Tissue engineering, along with other modern cell- and tissue-based health care technologies, depends on successful regulation of cell function by molecular means, including pharmacological agents, materials, and genetics. This regulation is generally mediated by cell receptor/ligand interactions providing primary targets for molecular intervention. While regulatory ligands may often be exogenous in nature, in the categories of endocrine and paracrine hormone systems, they are being increasingly appreciated as crucial in local control of cell and tissue function. Improvements in design of health care technologies involving autocrine ligand interactions with cell receptors should benefit from increased qualitative and quantitative understanding of the kinetic and transport processes governing these interactions. In this symposium paper we offer a concise overview of our recent efforts combining molecular cell biology and engineering approaches to increase the understanding of how molecular and cellular parameters may be manipulated for improved control of cell and tissue function regulated by autocrine ligands.

  10. Molecular approaches in pig breeding to improve meat quality.

    PubMed

    Davoli, Roberta; Braglia, Silvia

    2007-12-01

    This article reviews the advances in molecular genetics that have led to the identification of genes and markers associated with meat quality in pig. The development of a considerable number of annotated livestock genome sequences represents an incredibly rich source of information that can be used to identify candidate genes responsible for complex traits and quantitative trait loci effects. In pig, the huge amount of information emerging from the study of the genome has helped in the acquisition of new knowledge concerning biological systems and it is opening new opportunities for the genetic selection of this specie. Among the new fields of genomics recently developed, functional genomics and proteomics that allow considering many genes and proteins at the same time are very useful tools for a better understanding of the function and regulation of genes, and how these participate in complex networks controlling the phenotypic characteristics of a trait. In particular, global gene expression profiling at the mRNA and protein level can provide a better understanding of gene regulation that underlies biological functions and physiology related to the delivery of a better pig meat quality. Moreover, the possibility to realize an integrated approach of genomics and proteomics with bioinformatics tools is essential to obtain a complete exploitation of the available molecular genetics information. The development of this knowledge will benefit scientists, industry and breeders considering that the efficiency and accuracy of the traditional pig selection schemes will be improved by the implementation of molecular data into breeding programs. PMID:18208864

  11. 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

  12. 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

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

    PubMed

    Ternovyĭ, K S

    1995-01-01

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

  14. 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

  15. A systematic molecular genetic approach to study mammalian germline development

    PubMed Central

    Abe, Kuniya; Ko, Minoru S. H.; MacGregor, Grant R.

    2011-01-01

    It is difficult to study gene expression in mammalian embryonic germ cells as PGCs constitute only a minor proportion of the mouse embryo. We have overcome this problem by using a novel combination of established molecular and transgenic approaches. A line of mice has been generated in which the cells of the germ lineage express the β-galactosidase reporter gene during embryogenesis. Using this line, germ cells have been purified to near homogeneity from embryos at discrete stages during germline development by use of a stain for β-gal activity and a fluorescence activated cell sorter. Subsequently, cDNA libraries have been constructed from each germ cell population using a modified lone-linker PCR strategy. These combined cDNA libraries represent genes expressed in PGCs during mammalian germline development. To facilitate a molecular genetic approach to studying mammalian germline development, these cDNA libraries will be pooled to form an arrayed, addressed reference embryonic germ cell cDNA library. In parallel with large-scale cDNA sequencing efforts, genes that are differentially expressed in germ cells will be identified by screening the reference library with probes generated by subtractive hybridization. Complementary DNAs identified using this approach will be analyzed by sequencing, database comparison, genomic mapping and in situ hybridization to ascertain the potential functional importance of each gene to germline development. In addition to providing a wealth of novel information regarding patterns of gene expression during mammalian germline development, these results will form the basis for future experiments to determine the function of these genes in this process. PMID:9853837

  16. [Modern evolutional developmental biology: mechanical and molecular genetic or phenotypic approaches?].

    PubMed

    Vorob'eva, É I

    2010-01-01

    Heightened interest in the evolutionary problems of developmental biology in the 1980s was due to the success of molecular genetics and disappointment in the synthetic theory of evolution, where the chapters of embryology and developmental biology seem to have been left out. Modern evo-devo, which turned out to be antipodean to the methodology of the synthetic theory of evolution, propagandized in the development of evolutionary problems only the mechanical and molecular genetic approach to the evolution of ontogenesis, based on cellular and intercellular interactions. The phonotypical approach to the evaluation of evolutionary occurrences in ontogenesis, which aids in the joining of the genetic and epigenetic levels of research, the theory of natural selection, the nomogenetic conception, and the problem of the wholeness of the organism in onto- and phylogenesis may be against this. The phenotypic approach to ontogenesis is methodologically the most perspective for evolutionary developmental biology.

  17. 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…

  18. Photoswitchable gel assembly based on molecular recognition.

    PubMed

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

    2012-01-03

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

  19. Photoswitchable gel assembly based on molecular recognition

    PubMed Central

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

    2012-01-01

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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. In search of molecular approaches to improving cancer therapy efficacy.

    PubMed

    Cherepenko, E; Telegeev, G

    2014-03-01

    The study of genome rearrangement sites using full genome sequences is an important approach to revealing the nature of cancer and finding effective ways for cancer treatment. The progress in DNA sequencing could make the procedure of whole genome reading close to routine procedure of lower cost. The personal analysis of rearranged ends (PARE) method used for rearrangement study is reviewed. PARE allows identifying of individual cancer biomarkers making personal medicine possible. Also, the progress in "liquid biopsy" technology based on detection of circulating tumor cells in the patient's blood is shortly summarized. Another important approach is the discovered phenomenon of synthetic lethality causing cancer cell death due to appropriate combination of mutations in different genes or inhibitors of their protein products. Studies of genome rearrangements and synthetic lethality are considered promising for the development of effective cancer treatment approaches.

  8. Organic-based molecular switches for molecular electronics.

    PubMed

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

    2011-10-01

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

  9. Genetic engineered molecular imaging probes for applications in cell therapy: emphasis on MRI approach

    PubMed Central

    Cho, In K; Wang, Silun; Mao, Hui; Chan, Anthony WS

    2016-01-01

    Recent advances in stem cell-based regenerative medicine, cell replacement therapy, and genome editing technologies (i.e. CRISPR-Cas 9) have sparked great interest in in vivo cell monitoring. Molecular imaging promises a unique approach to noninvasively monitor cellular and molecular phenomena, including cell survival, migration, proliferation, and even differentiation at the whole organismal level. Several imaging modalities and strategies have been explored for monitoring cell grafts in vivo. We begin this review with an introduction describing the progress in stem cell technology, with a perspective toward cell replacement therapy. The importance of molecular imaging in reporting and assessing the status of cell grafts and their relation to the local microenvironment is highlighted since the current knowledge gap is one of the major obstacles in clinical translation of stem cell therapy. Based on currently available imaging techniques, we provide a brief discussion on the pros and cons of each imaging modality used for monitoring cell grafts with particular emphasis on magnetic resonance imaging (MRI) and the reporter gene approach. Finally, we conclude with a comprehensive discussion of future directions of applying molecular imaging in regenerative medicine to emphasize further the importance of correlating cell graft conditions and clinical outcomes to advance regenerative medicine. PMID:27766183

  10. 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

  11. Improving structure-based function prediction using molecular dynamics

    PubMed Central

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

    2009-01-01

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

  12. Detection of selection utilizing molecular phylogenetics: a possible approach.

    PubMed

    Yang, Ming; Wyckoff, Gerald J

    2011-05-01

    The neutral theory of molecular evolution (Kimura 1985) is the basis for most current statistical tests for detecting selection, mainly using polymorphism data within species, divergence data between species, and/or genomic structures like linkage disequilibrium (Wang et al. 2006). In most cases informative tests can only be constructed with ample variations within these parameters and many common tests are difficult to formulate when identity-by-descent is not clear, for example in gene families or repetitive elements. With the current progress being made toward whole-genome sequencing and re-sequencing efforts, as well as protein sequencing via tandem mass spectrometry where genomic sequencing is lacking, we felt it was necessary to re-visit possible methods for rapid screening and detection of evolutionary outliers. These outliers might be of interest for other research, such as candidate gene association studies or genome annotations, drug- and disease-target searches, and functional studies. We focused on methods that would work on both protein and nucleotide data, could be used on large gene or protein domain families, and could be generated quickly in order for "first pass" annotation of large scale data. For these reasons, we chose properties of trees generated routinely in molecular phylogenetic studies; genetic distance, tree shape and balance, and internal node statistics (Heard 1992). Our current research looking at protein domain family data and phylogenetic trees from PFAM (Finn et al. 2008) suggests this approach towards detecting evolutionary outliers is feasible, but additional work will be necessary to determine the parameters that suggest either positive or negative selection is occurring in specific gene families. This is particularly true when other factors such as rapid duplication and deletion of genes containing these domains is taking place, and we suggest phylogenetic statistics may be useful in combination with existing methodologies for

  13. 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 .

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. Molecular approaches to improve rice abiotic stress tolerance.

    PubMed

    Mizoi, Junya; Yamaguchi-Shinozaki, Kazuko

    2013-01-01

    Abiotic stress is a major factor limiting productivity of rice crops in large areas of the world. Because plants cannot avoid abiotic stress by moving, they have acquired various mechanisms for stress tolerance in the course of their evolution. Enhancing or introducing such mechanisms in rice is one effective way to develop stress-tolerant cultivars. Based on physiological studies on stress responses, recent progress in plant molecular biology has enabled discovery of many genes involved in stress tolerance. These genes include regulatory genes, which regulate stress response (e.g., transcription factors and protein kinases), and functional genes, which protect the cell (e.g., enzymes for generating protective metabolites and proteins). Both kinds of genes are used to increase stress tolerance in rice. In addition, several quantitative trait loci (QTLs) associated with higher stress tolerance have been cloned, contributing to the discovery of significantly important genes for stress tolerance.

  19. 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)

  20. 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

  1. 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.

  2. Rational approaches to design of therapeutics targeting molecular markers.

    PubMed

    Klasa, R J; List, A F; Cheson, B D

    2001-01-01

    This paper introduces novel therapeutic strategies focusing on a molecular marker relevant to a particular hematologic malignancy. Four different approaches targeting specific molecules in unique pathways will be presented. The common theme will be rational target selection in a strategy that has reached the early phase of human clinical trial in one malignancy, but with a much broader potential applicability to the technology. In Section I Dr. Richard Klasa presents preclinical data on the use of antisense oligonucleotides directed at the bcl-2 gene message to specifically downregulate Bcl-2 protein expression in non-Hodgkin's lymphomas and render the cells more susceptible to the induction of apoptosis. In Section II Dr. Alan List reviews the targeting of vascular endothelial growth factor (VEGF) and its receptor in anti-angiogenesis strategies for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In Section III Dr. Bruce Cheson describes recent progress in inhibiting cell cycle progression by selectively disrupting cyclin D1 with structurally unique compounds such as flavopiridol in mantle cell lymphoma as well as describing a new class of agents that affect proteasome degradation pathways.

  3. 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.

  4. 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

  5. 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

  6. 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

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2015-03-01

    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 A1 symmetry on the 9a1 momentum profile, which can be unravelled from considerations on the symmetry characteristics of orbitals and their energy spacing.

  10. 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.

  11. Feature activated molecular dynamics: an efficient approach for atomistic simulation of solid-state aggregation phenomena.

    PubMed

    Prasad, Manish; Sinno, Talid

    2004-11-01

    An efficient approach is presented for performing efficient molecular dynamics simulations of solute aggregation in crystalline solids. The method dynamically divides the total simulation space into "active" regions centered about each minority species, in which regular molecular dynamics is performed. The number, size, and shape of these regions is updated periodically based on the distribution of solute atoms within the overall simulation cell. The remainder of the system is essentially static except for periodic rescaling of the entire simulation cell in order to balance the pressure between the isolated molecular dynamics regions. The method is shown to be accurate and robust for the Environment-Dependant Interatomic Potential (EDIP) for silicon and an Embedded Atom Method potential (EAM) for copper. Several tests are performed beginning with the diffusion of a single vacancy all the way to large-scale simulations of vacancy clustering. In both material systems, the predicted evolutions agree closely with the results of standard molecular dynamics simulations. Computationally, the method is demonstrated to scale almost linearly with the concentration of solute atoms, but is essentially independent of the total system size. This scaling behavior allows for the full dynamical simulation of aggregation under conditions that are more experimentally realizable than would be possible with standard molecular dynamics.

  12. Understanding polycaroboxylate interactions with counterions: A molecular modeling approach

    SciTech Connect

    Fitzwater, S.; Freeman, M.B.

    1993-12-31

    Low molecular weight polycarboyxlates, such as poly(acrylic acid), have utility as dispersants in a variety of commercial applications including home laundry detergents, mineral processing and water treatment. In general, counterions (Ca, Mg, Fe, etc.) are unavoidable in these applications and often dictate the polymer composition and molecular weight necessary for successful performance. The authors have been investigating the interaction of polycarboxylates with counterions in order to better understand how that interaction impacts on the dispersant properties of a polymer. Using computer modeling, it can be seen how molecular geometry, molecular dynamics, and the shape/polarity of the molecular surface are affected by counterion binding and polymer composition. The authors can then combine information from the modeling with experimental information and literature concepts to provide a direction toward the synthesis of improved low molecular weight polycarboxylate dispersants.

  13. 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

  14. Molecular Approaches to Studying Microbial Communities: Targeting the 16S Ribosomal RNA Gene.

    PubMed

    Fukuda, Kazumasa; Ogawa, Midori; Taniguchi, Hatsumi; Saito, Mitsumasa

    2016-09-01

    Culture-independent methods to detect microorganisms have been developed in parallel with traditional culture-based methods ever since the classification of bacteria based on 16S rRNA gene sequences was advocated in the 1970s. The development and the prevalence of culture-independent molecular technologies have provided revolutionary progress in microbial studies. The development of these technologies contributes significantly to the research of microorganisms that cannot be detected by traditional methods such as culture-dependent methods.Many molecular methods targeting the 16S rRNA gene, such as fluorescence in situ hybridization (FISH), quantitative PCR, terminal restriction fragment length polymorphism (T-RFLP), denaturing-gradient gel electrophoresis (DGGE), clone library analysis, and next-generation DNA sequencing (NGS) technologies, have been applied to various microbial studies. Notably, the advent of NGS technologies enabled a large-scale research of the bacterial community. Many recent studies using the NGS technologies have revealed that a larger number of bacteria and taxa than previously thought inhabit various parts of the human body and various places on the earth. The principles and characteristics of each molecular method are different, and each method possesses individual advantages; for example target specificity, comprehensiveness, rapidness, and cost efficiency. Therefore it is important that the methods used in studies are suitable for the objective and materials. Herein, we highlights molecular approaches targeting the 16S rRNA gene in bacterial community analysis, and focuses on the advantages and limitations of each technology. PMID:27627970

  15. [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.

  16. [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

  17. 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…

  18. 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

  19. Understanding molecular identification and polyphasic taxonomic approaches for genetic relatedness and phylogenetic relationships of microorganisms.

    PubMed

    Das, Surajit; Dash, Hirak R; Mangwani, Neelam; Chakraborty, Jaya; Kumari, Supriya

    2014-08-01

    The major proportion of earth's biological diversity is inhabited by microorganisms and they play a useful role in diversified environments. However, taxonomy of microorganisms is progressing at a snail's pace, thus less than 1% of the microbial population has been identified so far. The major problem associated with this is due to a lack of uniform, reliable, advanced, and common to all practices for microbial identification and systematic studies. However, recent advances have developed many useful techniques taking into account the house-keeping genes as well as targeting other gene catalogues (16S rRNA, rpoA, rpoB, gyrA, gyrB etc. in case of bacteria and 26S, 28S, β-tubulin gene in case of fungi). Some uncultivable approaches using much advanced techniques like flow cytometry and gel based techniques have also been used to decipher microbial diversity. However, all these techniques have their corresponding pros and cons. In this regard, a polyphasic taxonomic approach is advantageous because it exploits simultaneously both conventional as well as molecular identification techniques. In this review, certain aspects of the merits and limitations of different methods for molecular identification and systematics of microorganisms have been discussed. The major advantages of the polyphasic approach have also been described taking into account certain groups of bacteria as case studies to arrive at a consensus approach to microbial identification.

  20. Molecular basis of glyphosate resistance-different approaches through protein engineering.

    PubMed

    Pollegioni, Loredano; Schonbrunn, Ernst; Siehl, Daniel

    2011-08-01

    Glyphosate (N-phosphonomethyl-glycine) is the most widely 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 attributable to the high specificity of glyphosate for the plant enzyme enolpyruvyl shikimate-3-phosphate synthase in the shikimate pathway, leading to the biosynthesis of aromatic amino acids. Starting in 1996, transgenic glyphosate-resistant plants were introduced, thus allowing application of the herbicide to the crop (post-emergence) to remove emerged weeds without crop damage. This review focuses on 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 a rationale for the means by which the modifications made have had their intended effect.

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

    PubMed

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

    2013-06-27

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

  2. 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

  3. 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

  4. Toxin-Based Therapeutic Approaches

    PubMed Central

    Shapira, Assaf; Benhar, Itai

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

  5. 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.

  6. 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…

  7. [Transnasal endoscopic approaches to the cranial base].

    PubMed

    Lysoń, Tomasz; Sieśkiewicz, Andrzej; Rutkowski, Robert; Kochanowicz, Jan; Turek, Grzegorz; Rogowski, Marek; Mariak, Zenon

    2013-01-01

    Recent advances in surgical endoscopy have made it possible to reach nearly the whole cranial base through a transnasal approach. These 'expanded approaches' lead to the frontal sinuses, the cribriform plate and planum sphenoidale, the suprasellar space, the clivus, odontoid and atlas. By pointing the endoscope laterally, the surgeon can explore structures in the coronal plane such as the cavernous sinuses, the pyramid and Meckel cave, the sphenopalatine and subtemporal fossae, and even the middle fossa and the orbit. The authors of this contribution use most of these approaches in their endoscopic skull base surgery. The purpose of this contribution is to review the hitherto established endoscopic approaches to the skull base and to illustrate them with photographs obtained during self-performed procedures and/or cadaver studies. PMID:23487296

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

    PubMed

    Chen, Z Jeffrey

    2013-07-01

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

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

    PubMed

    Chen, Z Jeffrey

    2013-07-01

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

  10. Optical materials based on molecular nanoparticles.

    PubMed

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

    2012-01-21

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

  11. Fragment-based approaches and computer-aided drug discovery.

    PubMed

    Rognan, Didier

    2012-01-01

    Fragment-based design has significantly modified drug discovery strategies and paradigms in the last decade. Besides technological advances and novel therapeutic avenues, one of the most significant changes brought by this new discipline has occurred in the minds of drug designers. Fragment-based approaches have markedly impacted rational computer-aided design both in method development and in applications. The present review illustrates the importance of molecular fragments in many aspects of rational ligand design, and discusses how thinking in "fragment space" has boosted computational biology and chemistry. PMID:21710380

  12. Molecular approaches for inferring evolutionary relationships among protistan parasites.

    PubMed

    Barta, J R

    2001-11-22

    Within the diverse group of parasites broadly recognized as protists, there are limited morphological characters that can be used to distinguish species and even fewer characters that can infer evolutionary relationships among species. For this reason, molecular data are commonly used to infer relationships among species and strains. These studies most commonly rely on sequences associated with the ribosomal RNA genes but increasingly other nuclear, mitochondrial or plastid genes are contributing data. Molecular systematics has been invaluable in expanding the range of characters that are available for inferring relationships among protistan taxa. As an adjunct to morphological characters, sequence data allow us to better understand the evolutionary history of this group of parasites and thereby erect a well-supported taxonomic framework that reflects these historical relationships. Importantly, the predictive nature of such a framework can aid the search for therapeutic compounds (e.g. via shared biochemical pathways) and highlight organisms that should be tested for cross-reactivity in immunological or molecular diagnostic methods (e.g. use of the closest relatives to assess test specificity). For emergent and poorly known parasites, molecular characterization and placement within the broader phylogenetic framework can help predict likely life history traits, including possible or likely definitive hosts.

  13. 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

  14. Integrating Survey and Molecular Approaches to Better Understand Wildlife Disease Ecology

    PubMed Central

    Cowled, Brendan D.; Ward, Michael P.; Laffan, Shawn W.; Galea, Francesca; Garner, M. Graeme; MacDonald, Anna J.; Marsh, Ian; Muellner, Petra; Negus, Katherine; Quasim, Sumaiya; Woolnough, Andrew P.; Sarre, Stephen D.

    2012-01-01

    Infectious wildlife diseases have enormous global impacts, leading to human pandemics, global biodiversity declines and socio-economic hardship. Understanding how infection persists and is transmitted in wildlife is critical for managing diseases, but our understanding is limited. Our study aim was to better understand how infectious disease persists in wildlife populations by integrating genetics, ecology and epidemiology approaches. Specifically, we aimed to determine whether environmental or host factors were stronger drivers of Salmonella persistence or transmission within a remote and isolated wild pig (Sus scrofa) population. We determined the Salmonella infection status of wild pigs. Salmonella isolates were genotyped and a range of data was collected on putative risk factors for Salmonella transmission. We a priori identified several plausible biological hypotheses for Salmonella prevalence (cross sectional study design) versus transmission (molecular case series study design) and fit the data to these models. There were 543 wild pig Salmonella observations, sampled at 93 unique locations. Salmonella prevalence was 41% (95% confidence interval [CI]: 37–45%). The median Salmonella DICE coefficient (or Salmonella genetic similarity) was 52% (interquartile range [IQR]: 42–62%). Using the traditional cross sectional prevalence study design, the only supported model was based on the hypothesis that abundance of available ecological resources determines Salmonella prevalence in wild pigs. In the molecular study design, spatial proximity and herd membership as well as some individual risk factors (sex, condition score and relative density) determined transmission between pigs. Traditional cross sectional surveys and molecular epidemiological approaches are complementary and together can enhance understanding of disease ecology: abundance of ecological resources critical for wildlife influences Salmonella prevalence, whereas Salmonella transmission is driven by

  15. 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

  16. Molecular Nanocapsules Based on Amphiphilic Hyperbranched Polyglycerols.

    PubMed

    Sunder; Krämer; Hanselmann; Mülhaupt; Frey

    1999-12-01

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

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

    PubMed

    Diaz-Cano, Salvador J

    2015-01-01

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

  18. 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

  19. 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

  20. 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.

  1. Polarizing properties of molecular ensembles: new approaches to calculations

    NASA Astrophysics Data System (ADS)

    Bokarev, Andrey N.; Plastun, Inna L.

    2016-04-01

    Polarizing properties of molecular ensembles with different structures are investigated by numerical simulation. Carbon nanotubes with zigzag configuration and nucleobases are considered. By numerical simulation total polarizability is investigated for different structures of molecules ensembles. New semi-analytical procedure for calculation of total polarizability for ensembles with different configuration is offered and tested by its application to ensembles which contain single-wall carbon nanotubes and nucleobases.

  2. 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}

  3. 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.

  4. 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.

  5. A fully first-principles approach to the Molecular Kondo problem

    NASA Astrophysics Data System (ADS)

    Soriano, Maria; Jacob, David; Palacios, Juan José; Atomelix Team

    2015-03-01

    There has been a great effort in recent years to understand the emerging Kondo-like resonances in different magnetic molecules such as MnPc. Theoretical approaches based on atomic models have proven to be very useful for the study of this phenomenon when the magnetic moment is essentially localized on a magnetic atom. Nevertheless the Kondo effect can arise in pure carbon-based systems as has been demonstrated experimentally in fullerenes and carbon nanotubes. In this communication we present a multiorbital Anderson model where the orbitals are not atomic but molecular orbitals. This model is fully obtained from Density Functional Theory calculation in combination with Green's functions methodologies. Standard impurity solver techniques are used to solve the model which is applied to fullerenes and other nanographene structures.

  6. 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''.

  7. 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.

  8. 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.

  9. Molecular Bases of Cutaneous and Uveal Melanomas

    PubMed Central

    Gaudi, Sudeep; Messina, Jane L.

    2011-01-01

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

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

    SciTech Connect

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

    2008-03-28

    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(H{sub 2}O){sub 6}{sup 2+/3+} and Ru(H{sub 2}O){sub 6}{sup 2+/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.

  11. 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.

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

    PubMed

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

    2015-02-01

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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Quantum mechanics-molecular dynamics approach to the interpretation of x-ray absorption spectra.

    PubMed

    Kuzmin, A; Evarestov, R A

    2009-02-01

    The quantum mechanics-molecular dynamics approach to the simulation of configuration-averaged EXAFS spectra is proposed, and its application is discussed for the example of the Ti K-edge EXAFS spectrum in cubic perovskite SrTiO(3). Proper use of ab initio quantum mechanics allows a number of empirical parameters, used in the molecular dynamics simulation, to be reduced, whereas the molecular dynamics allows us to account for temperature effects. All together, the approach provides a way of accounting for static and dynamic disorder in EXAFS signals from the coordination shells above the first one, where many-atom (multiple-scattering) effects are often important.

  2. 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)

  3. 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…

  4. Ugi-based approaches to quinoxaline libraries.

    PubMed

    Azuaje, Jhonny; El Maatougui, Abdelaziz; García-Mera, Xerardo; Sotelo, Eddy

    2014-08-11

    An expedient and concise Ugi-based unified approach for the rapid assembly of quinoxaline frameworks has been developed. This convergent and versatile method uses readily available commercial reagents, does not require advanced intermediates, and exhibits excellent bond-forming efficiency, thus exemplifying the operationally simple synthesis of quinoxaline libraries.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. A dual input DNA-based molecular switch.

    PubMed

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

    2014-11-01

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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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)

  20. 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…

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. New approach to energy transfer and quantum correlations in a molecular dimer

    NASA Astrophysics Data System (ADS)

    Saberi, M.; Bagheri Harouni, M.; Roknizadeh, R.; Latifi, H.

    2016-09-01

    The dynamics of single-excitation energy transfer in a molecular dimer interacting with a phonon bath is studied. Although there are exact numerical solutions for this system, we propose an approach that provides exact analytical results with few electronic degrees of freedom. This approach is based on considering the phonon subsystem in the coherent state representation. Applying this approach, the long-lived coherence time is evaluated in the weak and strong coupling regimes. Moreover, by calculating the quantum entanglement and global quantum discord, the time evolution of quantum correlations is examined. The effects of two parameters, electronic coupling strength and bath temperature, on the energy transfer and quantum correlations are studied. It is shown, in agreement with previous results, that the long-lived coherence time in the weak coupling regime is longer than in the strong coupling regime. Also, the increasing bath temperature gives rise to faster delocalization of energy transfer. Furthermore, it is illustrated that the bath temperature has a significant effect on the quantum entanglement with respect to the global quantum discord.

  6. 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.

  7. 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...

  8. Molecular weight enlargement--a molecular approach to continuous homogeneous catalysis.

    PubMed

    Janssen, Michèle; Müller, Christian; Vogt, Dieter

    2010-09-28

    Molecular weight enlargement (MWE) is an attractive method for homogeneous catalyst recycling. Applications of MWE in combination with either catalyst precipitation or nanofiltration have demonstrated their great potential as a method for process intensification in homogeneous catalysis. Selected, recent advances in MWE in combination with catalyst recovery are discussed, together with their implication for future developments. These examples demonstrate that this strategy is applicable in many different homogeneously catalyzed transformations.

  9. New vaccines for Mammalian allergy using molecular approaches.

    PubMed

    van Hage, Marianne; Pauli, Gabrielle

    2014-01-01

    Allergen-specific immunotherapy (SIT) offers a disease specific causative treatment by modifying the allergen-specific immune response allowing tolerance to higher doses of allergen and preventing progression of allergic diseases. It may be considered in patients allergic to furry animals. Current mammalian allergy vaccines are still prepared from relatively poorly defined allergen extracts and may induce immediate and late phase side effects. Although the mechanisms of SIT are still not fully understood, the more recent approaches report different strategies to reduce both allergen-specific IgE as well as T cell reactivity. The availability of recombinant allergens and synthetic peptides from the mammalian species has contributed to formulating new allergy vaccines to improve SIT for furry animal allergy. The majority of studies have focused on the major cat allergen Fel d 1 due to its extensive characterization in terms of IgE and T cell epitopes and to its dominant role in cat allergy. Here we review the most recent approaches, e.g., synthetic peptides, recombinant allergen derivatives, different hypoallergenic molecules, and recombinant allergens coupled to virus-like particles or immunomodulatory substances as well as strategies targeting the allergen to Fcγ receptors and the MHC class II pathway using a new route for administration. Many of the new vaccines hold promise but only a few of them have been investigated in clinical trials which will be the gold standard for evaluation of safety and efficacy in allergic patients.

  10. New Vaccines for Mammalian Allergy Using Molecular Approaches

    PubMed Central

    van Hage, Marianne; Pauli, Gabrielle

    2014-01-01

    Allergen-specific immunotherapy (SIT) offers a disease specific causative treatment by modifying the allergen-specific immune response allowing tolerance to higher doses of allergen and preventing progression of allergic diseases. It may be considered in patients allergic to furry animals. Current mammalian allergy vaccines are still prepared from relatively poorly defined allergen extracts and may induce immediate and late phase side effects. Although the mechanisms of SIT are still not fully understood, the more recent approaches report different strategies to reduce both allergen-specific IgE as well as T cell reactivity. The availability of recombinant allergens and synthetic peptides from the mammalian species has contributed to formulating new allergy vaccines to improve SIT for furry animal allergy. The majority of studies have focused on the major cat allergen Fel d 1 due to its extensive characterization in terms of IgE and T cell epitopes and to its dominant role in cat allergy. Here we review the most recent approaches, e.g., synthetic peptides, recombinant allergen derivatives, different hypoallergenic molecules, and recombinant allergens coupled to virus-like particles or immunomodulatory substances as well as strategies targeting the allergen to Fcγ receptors and the MHC class II pathway using a new route for administration. Many of the new vaccines hold promise but only a few of them have been investigated in clinical trials which will be the gold standard for evaluation of safety and efficacy in allergic patients. PMID:24672521

  11. 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.

  12. 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.

  13. 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

  14. Frame-Based Approach To Database Management

    NASA Astrophysics Data System (ADS)

    Voros, Robert S.; Hillman, Donald J.; Decker, D. Richard; Blank, Glenn D.

    1989-03-01

    Practical knowledge-based systems need to reason in terms of knowledge that is already available in databases. This type of knowledge is usually represented as tables acquired from external databases and published reports. Knowledge based systems provide a means for reasoning about entities at a higher level of abstraction. What is needed in many of today's expert systems is a link between the knowledge base and external databases. One such approach is a frame-based database management system. Package Expert (PEx) designs packages for integrated circuits. The thrust of our work is to bring together diverse technologies, data and design knowledge in a coherent system. PEx uses design rules to reason about properties of chips and potential packages, including dimensions, possible materials and packaging requirements. This information is available in existing databases. PEx needs to deal with the following types of information consistently: material databases which are in several formats; technology databases, also in several formats; and parts files which contain dimensional information. It is inefficient and inelegant to have rules access the database directly. Instead, PEx uses a frame-based hierarchical knowledge management approach to databases. Frames serve as the interface between rule-based knowledge and databases. We describe PEx and the use of frames in database retrieval. We first give an overview and the design evolution of the expert system. Next, we describe the system implementation. Finally, we describe how the rules in the expert system access the databases via frames.

  15. 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

  16. 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.

  17. 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

  18. Biotechnological and molecular approaches for vanillin production: a review.

    PubMed

    Kaur, Baljinder; Chakraborty, Debkumar

    2013-02-01

    Vanillin is one of the most widely used flavoring agents in the world. As the annual world market demand of vanillin could not be met by natural extraction, chemical synthesis, or tissue culture technology, thus biotechnological approaches may be replacement routes to make production of bio-vanillin economically viable. This review's main focus is to highlight significant aspects of biotechnology with emphasis on the production of vanillin from eugenol, isoeugenol, lignin, ferulic acid, sugars, phenolic stilbenes, vanillic acid, aromatic amino acids, and waste residues by applying fungi, bacteria, and plant cells. Production of biovanillin using GRAS lactic acid bacteria and metabolically engineered microorganisms, genetic organization of vanillin biosynthesis operons/gene cassettes and finally the stability of biovanillin generated through various biotechnological procedures are also critically reviewed in the later sections of the review.

  19. 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

  20. Molecular based treatment of oral cancer.

    PubMed

    Sudbø, Jon; Bryne, Magne; Mao, Li; Lotan, Reuben; Reith, Albrecht; Kildal, Wanja; Davidson, Ben; Søland, Tine M; Lippman, Scott M

    2003-12-01

    Given the increase in the age distribution of the population, an increase in cancer incidence rates are to be expected. Oral cancer is a disfiguring disease that continues to increase in incidence, particularly in the young, and to an extent that cannot be fully explained by increased exposure to known risk factors. Despite extensive research on treatment modalities towards oral cancer, the 5-year survival rate of this disease has not been improved over the last 4-5 decades. These facts strongly favour chemoprevention-systemic medication to revert, stop, or delay the carcinogenic process-as an approach to treating oral cancer. A chemopreventive approach to oral cancer most likely should encompass a combination of drugs targeting metabolic pathways relevant to oral carcinogenesis. Candidate drugs are retinoids and selective inhibitors of cyclooxygenase-2, epidermal growth factor receptor (EGFR), and peroxisome proliferator activated receptors (PPARs). Chemopreventive trials so far have used surrogate intermediate biomarkers as measurement of treatment effect. However, the efficiency of any drug for chemopreventive use should be assessed through a prospective randomized trial and evaluated by the only definitive end point for prevention of cancer, the incidence rates of new carcinomas. PMID:13679198

  1. 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...

  2. Prospecting Environmental Mycobacteria: combined molecular approaches reveal unprecedented diversity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmental mycobacteria (EM) include species commonly found in a variety of terrestrial and aquatic environments and encompass animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differen...

  3. New approaches to addiction treatment based on learning and memory.

    PubMed

    Kiefer, Falk; Dinter, Christina

    2013-01-01

    Preclinical studies suggest that physiological learning processes are similar to changes observed in addicts at the molecular, neuronal, and structural levels. Based on the importance of classical and instrumental conditioning in the development and maintenance of addictive disorders, many have suggested cue-exposure-based extinction training of conditioned, drug-related responses as a potential new treatment of addiction. It may also be possible to facilitate this extinction training with pharmacological compounds that strengthen memory consolidation during cue exposure. Another potential therapeutic intervention would be based on the so-called reconsolidation theory. According to this hypothesis, already-consolidated memories return to a labile state when reactivated, allowing them to undergo another phase of consolidation-reconsolidation, which can be pharmacologically manipulated. These approaches suggest that the extinction of drug-related memories may represent a viable treatment strategy in the future treatment of addiction.

  4. New approaches to addiction treatment based on learning and memory.

    PubMed

    Kiefer, Falk; Dinter, Christina

    2013-01-01

    Preclinical studies suggest that physiological learning processes are similar to changes observed in addicts at the molecular, neuronal, and structural levels. Based on the importance of classical and instrumental conditioning in the development and maintenance of addictive disorders, many have suggested cue-exposure-based extinction training of conditioned, drug-related responses as a potential new treatment of addiction. It may also be possible to facilitate this extinction training with pharmacological compounds that strengthen memory consolidation during cue exposure. Another potential therapeutic intervention would be based on the so-called reconsolidation theory. According to this hypothesis, already-consolidated memories return to a labile state when reactivated, allowing them to undergo another phase of consolidation-reconsolidation, which can be pharmacologically manipulated. These approaches suggest that the extinction of drug-related memories may represent a viable treatment strategy in the future treatment of addiction. PMID:21735361

  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. Endometriosis: a new cellular and molecular genetic approach for understanding the pathogenesis and evolutivity.

    PubMed

    Bouquet De Jolinière, Jean; Ayoubi, Jean Marc Bernard; Gianaroli, Luca; Dubuisson, Jean Bernard; Gogusev, Jean; Feki, Anis

    2014-01-01

    Endometriosis is a benign disease with high prevalence in women of reproductive age estimated between 10 and 15% and is associated with considerable morbidity. Its etiology and pathogenesis are controversial but it is believed to involve multiple genetic, environmental, immunological, angiogenic, and endocrine processes. Altered expressions of growth factors, cytokines, adhesion molecules, matrix metalloproteinases, and enzymes for estrogen synthesis and metabolism have been frequently observed in this condition. The possibility of genetic basis of endometriosis is demonstrated in studies of familial disease, in which the incidence of endometriosis is higher for first-degree relatives of probands as compared to controls. This review describes mainly the cellular, cytochemical, cytogenetic, and molecular genetic features of endometriotic lesions and cultured endometriotic cells. In attempts to identify candidate gene (s) involved in the pathogenesis of endometriosis, a tissue-based approaches including conventional cytogenetics (RHG-banding), loss of heterozygosity (LOH), and comparative genomic hybridization (CGH) were employed. In addition to the karyotypic anomalies, consistent chromosome instability was confirmed by CGH and fluorescence in situ hybridization (FISH). The nature and significance of the molecular genetic aberrations in relation to the locations and function of oncogenes and tumor suppressor genes will be discussed. At last, a possible pathogenic role of embryonic duct remnants was observed in seven female fetal reproductive tract in endometriosis and may induce a discussion about the beginning of ovarian tumors and malignant proliferations. PMID:25593940

  7. Endometriosis: A New Cellular and Molecular Genetic Approach for Understanding the Pathogenesis and Evolutivity

    PubMed Central

    Bouquet De Jolinière, Jean; Ayoubi, Jean Marc Bernard; Gianaroli, Luca; Dubuisson, Jean Bernard; Gogusev, Jean; Feki, Anis

    2014-01-01

    Endometriosis is a benign disease with high prevalence in women of reproductive age estimated between 10 and 15% and is associated with considerable morbidity. Its etiology and pathogenesis are controversial but it is believed to involve multiple genetic, environmental, immunological, angiogenic, and endocrine processes. Altered expressions of growth factors, cytokines, adhesion molecules, matrix metalloproteinases, and enzymes for estrogen synthesis and metabolism have been frequently observed in this condition. The possibility of genetic basis of endometriosis is demonstrated in studies of familial disease, in which the incidence of endometriosis is higher for first-degree relatives of probands as compared to controls. This review describes mainly the cellular, cytochemical, cytogenetic, and molecular genetic features of endometriotic lesions and cultured endometriotic cells. In attempts to identify candidate gene (s) involved in the pathogenesis of endometriosis, a tissue-based approaches including conventional cytogenetics (RHG-banding), loss of heterozygosity (LOH), and comparative genomic hybridization (CGH) were employed. In addition to the karyotypic anomalies, consistent chromosome instability was confirmed by CGH and fluorescence in situ hybridization (FISH). The nature and significance of the molecular genetic aberrations in relation to the locations and function of oncogenes and tumor suppressor genes will be discussed. At last, a possible pathogenic role of embryonic duct remnants was observed in seven female fetal reproductive tract in endometriosis and may induce a discussion about the beginning of ovarian tumors and malignant proliferations. PMID:25593940

  8. 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

  9. Molecular approaches to solar energy conversion: the energetic cost of charge separation from molecular-excited states.

    PubMed

    Durrant, James R

    2013-08-13

    This review starts with a brief overview of the technological potential of molecular-based solar cell technologies. It then goes on to focus on the core scientific challenge associated with using molecular light-absorbing materials for solar energy conversion, namely the separation of short-lived, molecular-excited states into sufficiently long-lived, energetic, separated charges capable of generating an external photocurrent. Comparisons are made between different molecular-based solar cell technologies, with particular focus on the function of dye-sensitized photoelectrochemical solar cells as well as parallels with the function of photosynthetic reaction centres. The core theme of this review is that generating charge carriers with sufficient lifetime and a high quantum yield from molecular-excited states comes at a significant energetic cost-such that the energy stored in these charge-separated states is typically substantially less than the energy of the initially generated excited state. The role of this energetic loss in limiting the efficiency of solar energy conversion by such devices is emphasized, and strategies to minimize this energy loss are compared and contrasted.

  10. 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

  11. 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

  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. 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.

  14. 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.

  15. Alcoholism: a systems approach from molecular physiology to addictive behavior.

    PubMed

    Spanagel, Rainer

    2009-04-01

    Alcohol consumption is an integral part of daily life in many societies. The benefits associated with the production, sale, and use of alcoholic beverages come at an enormous cost to these societies. The World Health Organization ranks alcohol as one of the primary causes of the global burden of disease in industrialized countries. Alcohol-related diseases, especially alcoholism, are the result of cumulative responses to alcohol exposure, the genetic make-up of an individual, and the environmental perturbations over time. This complex gene x environment interaction, which has to be seen in a life-span perspective, leads to a large heterogeneity among alcohol-dependent patients, in terms of both the symptom dimensions and the severity of this disorder. Therefore, a reductionistic approach is not very practical if a better understanding of the pathological processes leading to an addictive behavior is to be achieved. Instead, a systems-oriented perspective in which the interactions and dynamics of all endogenous and environmental factors involved are centrally integrated, will lead to further progress in alcohol research. This review adheres to a systems biology perspective such that the interaction of alcohol with primary and secondary targets within the brain is described in relation to the behavioral consequences. As a result of the interaction of alcohol with these targets, alterations in gene expression and synaptic plasticity take place that lead to long-lasting alteration in neuronal network activity. As a subsequent consequence, alcohol-seeking responses ensue that can finally lead via complex environmental interactions to an addictive behavior.

  16. 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

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

    PubMed

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

    2008-01-01

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

  18. 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

  19. 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

  20. Molecular approaches to understand biomineralization of shell nacreous layer.

    PubMed

    Xie, Li-Ping; Zhu, Fang-Jie; Zhou, Yu-Juan; Yang, Chao; Zhang, Rong-Qing

    2011-01-01

    The nacreous layer of molluskan shells, which consists of highly oriented aragonitic crystals and an organic matrix (including chitin and proteins), is a product of biomineralization. This paper briefly introduces the recent research advances on nacre biomineralization of shells from bivalves and gastropods, which mainly focus on analysis of the micro- and nano-structure and components of shell nacreous layers, and investigations of the characteristics and functions of matrix proteins from nacre. Matrix proteins not only participate in construction of the organic nacre framework, but also control the nucleation and growth of aragonitic crystals, as well as determine the polymorph specificity of calcium carbonate in nacre. Moreover, the inorganic aragonite phase also plays an active role in organizing nacre microstructure. Based on these studies, several models to illustrate the formation mechanism related to lamellar nacre in bivalves, and columnar nacre in gastropods are introduced.

  1. Matched filter based iterative adaptive approach

    NASA Astrophysics Data System (ADS)

    Nepal, Ramesh; Zhang, Yan Rockee; Li, Zhengzheng; Blake, William

    2016-05-01

    Matched Filter sidelobes from diversified LPI waveform design and sensor resolution are two important considerations in radars and active sensors in general. Matched Filter sidelobes can potentially mask weaker targets, and low sensor resolution not only causes a high margin of error but also limits sensing in target-rich environment/ sector. The improvement in those factors, in part, concern with the transmitted waveform and consequently pulse compression techniques. An adaptive pulse compression algorithm is hence desired that can mitigate the aforementioned limitations. A new Matched Filter based Iterative Adaptive Approach, MF-IAA, as an extension to traditional Iterative Adaptive Approach, IAA, has been developed. MF-IAA takes its input as the Matched Filter output. The motivation here is to facilitate implementation of Iterative Adaptive Approach without disrupting the processing chain of traditional Matched Filter. Similar to IAA, MF-IAA is a user parameter free, iterative, weighted least square based spectral identification algorithm. This work focuses on the implementation of MF-IAA. The feasibility of MF-IAA is studied using a realistic airborne radar simulator as well as actual measured airborne radar data. The performance of MF-IAA is measured with different test waveforms, and different Signal-to-Noise (SNR) levels. In addition, Range-Doppler super-resolution using MF-IAA is investigated. Sidelobe reduction as well as super-resolution enhancement is validated. The robustness of MF-IAA with respect to different LPI waveforms and SNR levels is also demonstrated.

  2. Electrochemical Approaches to Aptamer-Based Sensing

    NASA Astrophysics Data System (ADS)

    Xiao, Yi; Plaxco, Kevin W.

    Motivated by the potential convenience of electronic detection, a wide range of electrochemical, aptamer-based sensors have been reported since the first was described only in 2005. Although many of these are simply electrochemical, aptamer-based equivalents of traditional immunochemical approaches (e.g., sandwich and competition assays employing electroactive signaling moieties), others exploit the unusual physical properties of aptamers, properties that render them uniquely well suited for application to impedance and folding-based electrochemical sensors. In particular, the ability of electrode-bound aptamers to undergo reversible, binding-induced folding provides a robust, reagentless means of transducing target binding into an electronic signal that is largely impervious to nonspecific signals arising from contaminants. This capability enables the direct detection of specific proteins at physiologically relevant, picomolar concentrations in blood serum and other complex, contaminant-ridden sample matrices.

  3. 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

  4. 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.

  5. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  7. Implementation of a molecular epidemiology approach to human pleural malignant mesothelioma.

    PubMed

    Puntoni, Riccardo; Filiberti, Rosangela; Cerrano, Paolo G; Neri, Monica; Andreatta, Rossana; Bonassi, Stefano

    2003-11-01

    The carcinogenic effect of asbestos has been reported in the literature since 40 years, and early studies describing the epidemic occurrence of malignant mesothelioma (MM) in asbestos workers, have become a paradigm of occupational cancer research. Research on MM was abandoned for many years since MM was considered as an asbestos-related disease, interesting only from a perspective of disease control and preventive policies. The introduction of new biological endpoints in the epidemiological studies has boosted research in the field, providing new tools for the study of emerging priority in cancer research and in public health. This approach, known as molecular epidemiology has a great potential in the study of MM, contributing to the understanding of susceptibility factors, to the evaluation of cancer risk in people occupationally or environmentally exposed to carcinogens, and to the enhancement of diagnosis and therapy. A comprehensive approach based on the use of banks of biological samples is presented and its advantages discussed here. The application of innovative endpoints, such as oncoproteins in biologic fluids, genetic polimorphisms, or gene function is discussed, and relevant literature reviewed.

  8. Advances in conservation endocrinology: the application of molecular approaches to the conservation of endangered species.

    PubMed

    Tubbs, Christopher; McDonough, Caitlin E; Felton, Rachel; Milnes, Matthew R

    2014-07-01

    Among the numerous societal benefits of comparative endocrinology is the application of our collective knowledge of hormone signaling towards the conservation of threatened and endangered species - conservation endocrinology. For several decades endocrinologists have used longitudinal hormone profiles to monitor reproductive status in a multitude of species. Knowledge of reproductive status among individuals has been used to assist in the management of captive and free-ranging populations. More recently, researchers have begun utilizing molecular and cell-based techniques to gain a more complete understanding of hormone signaling in wildlife species, and to identify potential causes of disrupted hormone signaling. In this review we examine various in vitro approaches we have used to compare estrogen receptor binding and activation by endogenous hormones and phytoestrogens in two species of rhinoceros; southern white and greater one-horned. We have found many of these techniques valuable and practical in species where access to research subjects and/or tissues is limited due to their conservation status. From cell-free, competitive binding assays to full-length receptor activation assays; each technique has strengths and weaknesses related to cost, sensitivity, complexity of the protocols, and relevance to in vivo signaling. We then present a novel approach, in which receptor activation assays are performed in primary cell lines derived from the species of interest, to minimize the artifacts of traditional heterologous expression systems. Finally, we speculate on the promise of next generation sequencing and transcriptome profiling as tools for characterizing hormone signaling in threatened and endangered species.

  9. 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

  10. 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.

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

    PubMed

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

    2006-11-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Bifurcation-based approach reveals synergism and optimal combinatorial perturbation.

    PubMed

    Liu, Yanwei; Li, Shanshan; Liu, Zengrong; Wang, Ruiqi

    2016-06-01

    Cells accomplish the process of fate decisions and form terminal lineages through a series of binary choices in which cells switch stable states from one branch to another as the interacting strengths of regulatory factors continuously vary. Various combinatorial effects may occur because almost all regulatory processes are managed in a combinatorial fashion. Combinatorial regulation is crucial for cell fate decisions because it may effectively integrate many different signaling pathways to meet the higher regulation demand during cell development. However, whether the contribution of combinatorial regulation to the state transition is better than that of a single one and if so, what the optimal combination strategy is, seem to be significant issue from the point of view of both biology and mathematics. Using the approaches of combinatorial perturbations and bifurcation analysis, we provide a general framework for the quantitative analysis of synergism in molecular networks. Different from the known methods, the bifurcation-based approach depends only on stable state responses to stimuli because the state transition induced by combinatorial perturbations occurs between stable states. More importantly, an optimal combinatorial perturbation strategy can be determined by investigating the relationship between the bifurcation curve of a synergistic perturbation pair and the level set of a specific objective function. The approach is applied to two models, i.e., a theoretical multistable decision model and a biologically realistic CREB model, to show its validity, although the approach holds for a general class of biological systems.

  17. 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.

  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. Recent advances in molecular recognition based on nanoengineered platforms.

    PubMed

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

    2014-04-15

    Nanoparticles and nanoengineered platforms have great potential for technologies involving biomoleuclar detection or cell-related biosensing, and have provided effective chemical interfaces for molecular recognition. Typically, chemists work on the modification of synthetic polymers or macromolecules, which they link to the nanoparticles by covalent or noncovalent approaches. The motivation for chemical modification is to enhance the selectivity and sensitivity, and to improve the biocompatibility for the in vivo applications. In this Account, we present recent advances in the development and application of chemical interfaces for molecular recognition for nanoparticles and nanoengineered platforms, in particular single-walled carbon nanotubes (SWNTs). We discuss emerging approaches for recognizing small molecules, glycosylated proteins, and serum biomarkers. For example, we compare and discuss detection methods for ATP, NO, H2O2, and monosaccharides for recent nanomaterials. Fluorometric detection appears to have great potential for quantifying concentration gradients and determining their location in living cells. For macromolecular detection, new methods for glycoprofiling using such interfaces appear promising, and benefit specifically from the potential elimination of cumbersome labeling and liberation steps during conventional analysis of glycans, augmenting the currently used mass spectrometry (MS), capillary electrophoresis (CE), and liquid chromatography (LC) methods. In particular, we demonstrated the great potential of fluorescent SWNTs for glycan-lectin interactions sensing. In this case, SWNTs are noncovalently functionalized to introduce a chelated nickel group. This group provides a docking site for the His-tagged lectin and acts as the signal modulator. As the nickel proximity to the SWNT surface changes, the fluorescent signal is increased or attenuated. When a free glycan or glycosylated probe interacts with the lectin, the signal increases and

  20. Quantum wavepacket ab initio molecular dynamics: an approach for computing dynamically averaged vibrational spectra including critical nuclear quantum effects.

    PubMed

    Sumner, Isaiah; Iyengar, Srinivasan S

    2007-10-18

    We have introduced a computational methodology to study vibrational spectroscopy in clusters inclusive of critical nuclear quantum effects. This approach is based on the recently developed quantum wavepacket ab initio molecular dynamics method that combines quantum wavepacket dynamics with ab initio molecular dynamics. The computational efficiency of the dynamical procedure is drastically improved (by several orders of magnitude) through the utilization of wavelet-based techniques combined with the previously introduced time-dependent deterministic sampling procedure measure to achieve stable, picosecond length, quantum-classical dynamics of electrons and nuclei in clusters. The dynamical information is employed to construct a novel cumulative flux/velocity correlation function, where the wavepacket flux from the quantized particle is combined with classical nuclear velocities to obtain the vibrational density of states. The approach is demonstrated by computing the vibrational density of states of [Cl-H-Cl]-, inclusive of critical quantum nuclear effects, and our results are in good agreement with experiment. A general hierarchical procedure is also provided, based on electronic structure harmonic frequencies, classical ab initio molecular dynamics, computation of nuclear quantum-mechanical eigenstates, and employing quantum wavepacket ab initio dynamics to understand vibrational spectroscopy in hydrogen-bonded clusters that display large degrees of anharmonicities.

  1. 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

  2. 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.

  3. 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.

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

    PubMed

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

    2014-10-16

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

  5. 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-...

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

    PubMed

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

    2015-06-01

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

  7. DNA signature-based approaches for bacterial detection and identification.

    PubMed

    Albuquerque, Pedro; Mendes, Marta V; Santos, Catarina L; Moradas-Ferreira, Pedro; Tavares, Fernando

    2009-06-01

    During the late eighties, environmental microbiologists realized the potential of the polymerase chain reaction (PCR) for the design of innovative approaches to study microbial communities or to detect and identify microorganisms in diverse and complex environments. In contrast to long-established methods of cultivation-based microbial identification, PCR-based techniques allow for the identification of microorganisms regardless of their culturability. A large number of reports have been published that describe PCR-inspired methods, frequently complemented by sequencing or hybridization profiling, to infer taxonomic and clonal microbial diversity or to detect and identify microorganisms using taxa-specific genomic markers. Typing methods have been particularly useful for microbial ecology-driven studies; however, they are not suitable for diagnostic purposes, such as the detection of specific species, strains or clones. Recently, comprehensive reviews have been written describing the panoply of typing methods available and describing their advantages and limitations; however, molecular approaches for bacterial detection and identification were either not considered or only vaguely discussed. This review focuses on DNA-based methods for bacterial detection and identification, highlighting strategies for selecting taxa-specific loci and emphasizing the molecular techniques and emerging technological solutions for increasing the detection specificity and sensitivity. The massive and increasing number of available bacterial sequences in databases, together with already employed bioinformatics tools, hold promise of more reliable, fast and cost-effective methods for bacterial identification in a wide range of samples in coming years. This tendency will foster the validation and certification of these methods and their routine implementation by certified diagnostic laboratories.

  8. 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…

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

    PubMed

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

    2012-11-11

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

  10. 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…

  11. 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.

  12. 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.

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

    PubMed

    Khavinson, V Kh; Lin'kova, N S

    2012-01-01

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

  14. 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.

  15. Theory of zwitterionic molecular-based organic magnets

    NASA Astrophysics Data System (ADS)

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

    2011-08-01

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

  16. 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

  17. 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

  18. 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

  19. Nanotechnology-based approaches in anticancer research.

    PubMed

    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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  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. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

    PubMed

    Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

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

    PubMed

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

    2012-09-01

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

  7. 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.

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

    PubMed

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

    2014-04-01

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

  9. Optically induced transport through semiconductor-based molecular electronics

    SciTech Connect

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

    2015-04-21

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

  10. 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.

  11. [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.

  12. 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

  13. [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

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

    PubMed

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

    2014-07-30

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

  15. Molecular imaging of cell-based cancer immunotherapy

    PubMed Central

    Liu, Gang; Swierczewska, Magdalena; Zhang, Xiaoming

    2011-01-01

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

  16. 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

  17. 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.

  18. Interactions between polymers and single-walled boron nitride nanotubes: a molecular dynamics simulation approach.

    PubMed

    Nasrabadi, Amir Taghavi; Foroutan, Masumeh

    2010-12-01

    In this work, we used a molecular dynamics (MD) simulation approach to investigate the interfacial binding of boron nitride nanotubes (BNNTs) with poly[m-phenylenevinylene-co-(2,5-dioctyloxy-p-phenylenevinylene)] (PmPV), polystyrene (PS), and polythiophene (PT). Quantum partial charges of BNNT-polymer composites were determined by density functional theory (DFT) calculations and then included in MD simulations. The interaction energy between nanotubes and polymer molecules was computed, and the morphology of polymers stacked onto the surface of the nanotubes was investigated based on the dihedral angle (θ). Our results confirm that the interaction energy is strongly influenced by the specific monomer structure of polymer and nanotube radius, but the influence of temperature is likely negligible. Among the investigated polymers, PT possesses the strongest adhesion to the BNNTs, followed by PmPV and PS. Moreover, the comparison of our results for BNNT-polymer composities with those of the similar carbon nanotube (CNT)-polymer composites reveals that the BNNT-polymer interactions are much stronger, which is the most important result of this work. This finding is also in good agreement with recent experimental observations. The higher values of interaction energy of BNNT-polymer composites suggest that the BNNTs could be more efficient nanofillers than the CNTs for nanocomposite reinforcement applications.

  19. A New Maximum Likelihood Approach for Free Energy Profile Construction from Molecular Simulations.

    PubMed

    Lee, Tai-Sung; Radak, Brian K; Pabis, Anna; York, Darrin M

    2013-01-01

    A novel variational method for construction of free energy profiles from molecular simulation data is presented. The variational free energy profile (VFEP) method uses the maximum likelihood principle applied to the global free energy profile based on the entire set of simulation data (e.g from multiple biased simulations) that spans the free energy surface. The new method addresses common obstacles in two major problems usually observed in traditional methods for estimating free energy surfaces: the need for overlap in the re-weighting procedure and the problem of data representation. Test cases demonstrate that VFEP outperforms other methods in terms of the amount and sparsity of the data needed to construct the overall free energy profiles. For typical chemical reactions, only ~5 windows and ~20-35 independent data points per window are sufficient to obtain an overall qualitatively correct free energy profile with sampling errors an order of magnitude smaller than the free energy barrier. The proposed approach thus provides a feasible mechanism to quickly construct the global free energy profile and identify free energy barriers and basins in free energy simulations via a robust, variational procedure that determines an analytic representation of the free energy profile without the requirement of numerically unstable histograms or binning procedures. It can serve as a new framework for biased simulations and is suitable to be used together with other methods to tackle with the free energy estimation problem.

  20. 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

  1. 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.

  2. 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

  3. Molecular approach and bacterial quality of drinking water of urban and rural communities in Egypt.

    PubMed

    Abo-Amer, Aly E; Soltan, El-Sayed M; Abu-Gharbia, Magdy A

    2008-09-01

    Water is necessary to life so when supplied as drinking water to consumers, a satisfactory quality must be maintained. In Egypt, infectious intestinal diseases are the major cause of hospitalization in almost all regions. The purpose of this study was to evaluate the microbiological quality of treated and untreated water samples from urban and rural communities. Thirty-five samples of treated (chlorinated) water from taps, 25 samples of bottled water and 15 samples of hand pump (untreated) water collected from different cities alongside the River Nile during the winter of 2007 were bacteriologically tested for safety as drinking water. This study indicated good quality of tap water and bottled water. The untreated water samples (hand pumps) were, however, slightly contaminated by faecal coliforms, faecal enterococci, Clostridium perfringens, Salmonella and Shigella. Consequently, the consumers in the villages receiving water through hand pumps are often exposed to the risk of water-borne diseases due to inadequate treatment of the raw water. Therefore, there are guidelines necessary to protect groundwater quality. Moreover, PCR-amplified by some functional gene fragments such as dctA, dcuB, frdA, dcuS and dcuR genes of the E. coli was adapted for use as a non-cultivation-based molecular approach for detection of E. coli populations from water samples without the need for pure and identified cultures.

  4. 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.

  5. 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.

  6. 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.

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

    DOE PAGES

    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

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

    PubMed Central

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-01-01

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

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

    PubMed

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-12-01

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

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

    PubMed

    Pickup, Barry T; Fowler, Patrick W; 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.

  11. 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.

  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.

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

    PubMed

    Zhou, Shunye; Li, Youyong; Hou, Tingjun

    2013-04-22

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

  14. Molecular Target Approaches in Head and Neck Cancer: EGFR and Beyond

    PubMed Central

    Harari, Paul M.; Wheeler, Deric L.; Grandis, Jennifer R.

    2011-01-01

    Approximately 50,000 new cases of head and neck squamous cell carcinoma (HNSCC) will be diagnosed in the United States (US) in 2009. Whereas the gradual decline in smoking rates in the US is a highly favorable trend, future global HNSCC incidence will likely reflect the increased marketing and penetration of tobacco products across several of our most populous countries. Although modern surgery, radiation and conventional chemotherapy strategies for HNSCC continue to provide gradual improvement in outcome, the first molecular targeting approach to demonstrate a survival advantage for HNSCC patients has recently emerged in the context of EGFR biology. The scientific background and current challenges accompanying this recent advance are described in this article as are several additional promising molecular targets for HNSCC. There is cautious anticipation that the logical advancement of molecular targeting agents in conjunction with radiation may afford increased cure rates and diminished normal tissue toxicity profiles for HNSCC patients over the years to come. PMID:19028347

  15. 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.

  16. 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.

  17. 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

  18. [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

  19. Transcriptomic and metabolomic approaches to investigate the molecular responses of human cell lines exposed to the flame retardant hexabromocyclododecane (HBCD).

    PubMed

    Zhang, Jinkang; Williams, Timothy D; Abdallah, Mohamed Abou-Elwafa; Harrad, Stuart; Chipman, James K; Viant, Mark R

    2015-12-01

    The potential for human exposure to the brominated flame retardant, hexabromocyclododecane (HBCD) has given rise to health concerns, yet there is relatively limited knowledge about its possible toxic effects and the underlying molecular mechanisms that may mediate any impacts on health. In this study, unbiased transcriptomic and metabolomic approaches were employed to investigate the potential molecular changes that could lead to the toxicity of HBCD under concentrations relevant to human exposure conditions using in vitro models. A concentration-dependent cytotoxic effect of HBCD to A549 and HepG2/C3A cells was observed based on MTT assays or CCK-8 assays with EC50 values of 27.4 μM and 63.0 μM, respectively. Microarray-based transcriptomics and mass spectrometry-based metabolomics revealed few molecular changes in A549 cells or HepG2/C3A cells following a 24-hour exposure to several sub-lethal concentrations (2 to 4000 nM) of HBCD. Quantification of the level of HBCD in the HepG2/C3A exposed cells suggested that the flame retardant was present at concentrations several orders of magnitude higher than those reported to occur in human tissues. We conclude that at the concentrations known to be achievable following exposure in humans, HBCD exhibits no detectable acute toxicity in A549 cells, representative of the lung, or in HepG2/C3A cells, that are hepatocytes with some xenobiotic metabolic capacity.

  20. 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.

  1. 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

  2. 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

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

    NASA Astrophysics Data System (ADS)

    Xiao, Tiejun; Song, Xueyu

    2013-03-01

    The reorganization energy of electron transfer processes in ionic fluids is studied under the linear response approximation using a molecule Debye-Hückel theory. Reorganization energies of some model reactants of electron transfer reactions in molten salts are obtained from molecular simulations and a molecule Debye-Hückel 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.

  4. 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

  5. Evaluating face trustworthiness: a model based approach.

    PubMed

    Todorov, Alexander; Baron, Sean G; Oosterhof, Nikolaas N

    2008-06-01

    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

  6. 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.

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

    PubMed

    Richters, Dorothee; Kühne, Thomas D

    2014-04-01

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

  8. Modelling of molecular phase transitions in pharmaceutical inhalation compounds: an in silico approach.

    PubMed

    Abdel-Halim, Heba; Traini, Daniela; Hibbs, David; Gaisford, Simon; Young, Paul

    2011-05-01

    Molecular dynamic simulations have been successfully utilised with molecular modelling to estimate the glass transition temperature (T(g)) of polymers. In this paper, we use a similar approach to predict the T(g) of a small pharmaceutical molecule, beclomethasone dipropionate (BDP). Amorphous beclomethasone dipropionate was prepared by spray-drying. The amorphous nature of the spray-dried material was confirmed with scanning electron microscopy, differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). Molecular models for amorphous BDP were constructed using the amorphous cell module in Discovery studio™. These models were used in a series of molecular dynamic simulations to predict the glass transition temperature. The T(g) of BDP was determined by isothermal-isobaric molecular dynamic simulations, and different thermodynamic parameters were obtained in the temperature range of -150 to 400°C. The discontinuity at a specific temperature in the plot of temperature versus amorphous cell volume (V) and density (ρ) was considered to be the simulated T(g.) The predicted T(g) from four different simulation runs was 63.8°C ± 2.7°C. The thermal properties of amorphous BDP were experimentally determined by DSC and the experimental T(g) was found to be ∼ 65°C, in good agreement with computational simulations.

  9. Translating clinical research of Molecular Biology into a personalized, multidisciplinary approach of colorectal cancer patients.

    PubMed

    Strambu, V; Garofil, D; Pop, F; Radu, P; Bratucu, M; Popa, F

    2014-03-15

    Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.

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

    PubMed

    Lin, Jia-Hui; Tseng, Wei-Lung

    2014-03-21

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

  11. 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.

  12. 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.

  13. 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.

  14. Paper-based molecular diagnostic for Chlamydia trachomatis

    PubMed Central

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

    2014-01-01

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

  15. 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.

  16. Kinetic modeling based probabilistic segmentation for molecular images.

    PubMed

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

    2008-01-01

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

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

    PubMed

    Jain, Ajay N

    2003-02-13

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

  18. Mating types in Paramecium and a molecular approach to their determination.

    PubMed

    Sawka, Natalia

    2012-01-01

    Mating types are expressed in ciliates for the duration of the mature period of their clonal cycle. During cell conjugation the reciprocal fertilization of complementary mating types takes place. Models of mating type determination in the Paramecium aurelia species complex based on classical genetics are reviewed including molecular aspects of the studies. PMID:22428300

  19. Molecular approaches to the photocatalytic reduction of carbon dioxide for solar fuels.

    PubMed

    Morris, Amanda J; Meyer, Gerald J; Fujita, Etsuko

    2009-12-21

    The scientific community now agrees that the rise in atmospheric CO(2), the most abundant green house gas, comes from anthropogenic sources such as the burning of fossil fuels. This atmospheric rise in CO(2) results in global climate change. Therefore methods for photochemically transforming CO(2) into a source of fuel could offer an attractive way to decrease atmospheric concentrations. One way to accomplish this conversion is through the light-driven reduction of carbon dioxide to methane (CH(4(g))) or methanol (CH(3)OH((l))) with electrons and protons derived from water. Existing infrastructure already supports the delivery of natural gas and liquid fuels, which makes these possible CO(2) reduction products particularly appealing. This Account focuses on molecular approaches to photochemical CO(2) reduction in homogeneous solution. The reduction of CO(2) by one electron to form CO(2)(*-) is highly unfavorable, having a formal reduction potential of -2.14 V vs SCE. Rapid reduction requires an overpotential of up to 0.6 V, due at least in part to the kinetic restrictions imposed by the structural difference between linear CO(2) and bent CO(2)(*-). An alternative and more favorable pathway is to reduce CO(2) though proton-assisted multiple-electron transfer. The development of catalysts, redox mediators, or both that efficiently drive these reactions remains an important and active area of research. We divide these reactions into two class types. In Type I photocatalysis, a molecular light absorber and a transition metal catalyst work in concert. We also consider a special case of Type 1 photocatalysis, where a saturated hydrocarbon links the catalyst and the light absorber in a supramolecular compound. In Type II photocatalysis, the light absorber and the catalyst are the same molecule. In these reactions, transition-metal coordination compounds often serve as catalysts because they can absorb a significant portion of the solar spectrum and can promote activation

  20. Molecular modeling for screening environmental chemicals for estrogenicity: use of the toxicant-target approach.

    PubMed

    Rabinowitz, James R; Little, Stephen B; Laws, Susan C; Goldsmith, Michael-Rock

    2009-09-01

    There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the preliminary evaluation of risk and the establishment of priorities for obtaining missing data for environmental chemicals. The differential step in many mechanisms of toxicity may be generalized as the interaction between a small molecule (a potential toxicant) and one or more macromolecular targets. An approach based on computation of the interaction between a potential molecular toxicant and a library of macromolecular targets of toxicity has been proposed for preliminary chemical screening. In the current study, the interaction between a series of environmentally relevant chemicals and models of the rat estrogen receptors (ER) was computed and the results compared to an experimental data set of their relative binding affinities. The experimental data set consists of 281 chemicals, selected from the U.S. EPA's Toxic Substances Control Act (TSCA) inventory, that were initially screened using the rat uterine cytosolic ER-competitive binding assay. Secondary analysis, using Lineweaver-Burk plots and slope replots, was applied to confirm that only 15 of these test chemicals were true competitive inhibitors of ER binding with experimental inhibition constants (K(i)) less than 100 microM. Two different rapid computational docking methods have been applied. Each provides a score that is a surrogate for the strength of the interaction between each ligand-receptor pair. Using the score that indicates the strongest interaction for each pair, without consideration of the geometry of binding between the toxicant and the target, all of the active molecules were discovered in the first 16% of the chemicals. When a filter is applied on the basis of the geometry of a simplified pharmacophore for binding to

  1. Molecular modeling for screening environmental chemicals for estrogenicity: use of the toxicant-target approach.

    PubMed

    Rabinowitz, James R; Little, Stephen B; Laws, Susan C; Goldsmith, Michael-Rock

    2009-09-01

    There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the preliminary evaluation of risk and the establishment of priorities for obtaining missing data for environmental chemicals. The differential step in many mechanisms of toxicity may be generalized as the interaction between a small molecule (a potential toxicant) and one or more macromolecular targets. An approach based on computation of the interaction between a potential molecular toxicant and a library of macromolecular targets of toxicity has been proposed for preliminary chemical screening. In the current study, the interaction between a series of environmentally relevant chemicals and models of the rat estrogen receptors (ER) was computed and the results compared to an experimental data set of their relative binding affinities. The experimental data set consists of 281 chemicals, selected from the U.S. EPA's Toxic Substances Control Act (TSCA) inventory, that were initially screened using the rat uterine cytosolic ER-competitive binding assay. Secondary analysis, using Lineweaver-Burk plots and slope replots, was applied to confirm that only 15 of these test chemicals were true competitive inhibitors of ER binding with experimental inhibition constants (K(i)) less than 100 microM. Two different rapid computational docking methods have been applied. Each provides a score that is a surrogate for the strength of the interaction between each ligand-receptor pair. Using the score that indicates the strongest interaction for each pair, without consideration of the geometry of binding between the toxicant and the target, all of the active molecules were discovered in the first 16% of the chemicals. When a filter is applied on the basis of the geometry of a simplified pharmacophore for binding to

  2. 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.

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

    PubMed

    Ioannidis, J P A

    2007-05-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. 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.

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

    PubMed

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

    2004-06-18

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

  8. Resolving self-association of a therapeutic antibody by formulation optimization and molecular approaches.

    PubMed

    Casaz, Paul; Boucher, Elisabeth; Wollacott, Rachel; Pierce, Brian G; Rivera, Rachel; Sedic, Maja; Ozturk, Sadettin; Thomas, William D; Wang, Yang

    2014-01-01

    A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association, formation of a semi-solid gel or "gelation." Therapeutic monoclonal antibody C4 was isolated from human B cells based on its strong potency in neutralizing bacterial toxin in animal models. The purified antibody possessed the unusual property of forming a firm, opaque white gel when it was formulated at concentrations >30 mg/mL and the temperature was <6°C. Gel formation was reversible with temperature. Gelation was affected by salt concentration or pH, suggesting an electrostatic interaction between IgG monomers. A comparison of the C4 amino acid sequences to consensus germline sequences revealed differences in framework regions. A C4 variant in which the framework sequence was restored to the consensus germline sequence did not gel at 100 mg/mL at temperatures as low as 1°C. Additional genetic analysis was used to predict the key residue(s) involved in the gelation. Strikingly, a single substitution in the native antibody, replacing heavy chain glutamate 23 with lysine (E23K), was sufficient to prevent gelation. These results indicate that the framework region is involved in intermolecular interactions. The temperature dependence of gelation may be related to conformational changes near glutamate 23 or the regions it interacts with. Molecular engineering of the framework can be an effective approach to resolve the solubility issues of therapeutic antibodies. PMID:25484044

  9. A synthetic approach to a molecular crank mechanism: toward intramolecular motion transformation between rotation and translation.

    PubMed

    Okuno, Erika; Hiraoka, Shuichi; Shionoya, Mitsuhiko

    2010-05-01

    A molecular crank mechanism that enables transformation between rotational and translational motions was designed and synthesized. This molecule consists of a molecular ball bearing as the rotational part in which two disk-shaped rotors can rotate relative to each other through ligand exchange and flipping motion, and a [2]rotaxane as a translational part in which an axle molecule can move back-and-forth through the cavity of a crown ether-based macrocycle. (1)H NMR analysis revealed that these two motions influence each other.

  10. Free Energy Calculations using a Swarm-Enhanced Sampling Molecular Dynamics Approach.

    PubMed

    Burusco, Kepa K; Bruce, Neil J; Alibay, Irfan; Bryce, Richard A

    2015-10-26

    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.

  11. 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.

  12. 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.

  13. 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

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

    PubMed

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

    2014-06-01

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

  15. 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.

  16. A molecular approach to Cu doped ZnO nanorods with tunable dopant content.

    PubMed

    Pashchanka, Mikhail; Hoffmann, Rudolf C; Gurlo, Aleksander; Swarbrick, Janine C; Khanderi, Jayaprakash; Engstler, Jörg; Issanin, Alexander; Schneider, Jörg J

    2011-04-28

    A novel molecular approach to the synthesis of polycrystalline Cu-doped ZnO rod-like nanostructures with variable concentrations of introduced copper ions in ZnO host matrix is presented. Spectroscopic (PLS, variable temperature XRD, XPS, ELNES, HERFD) and microscopic (HRTEM) analysis methods reveal the +II oxidation state of the lattice incorporated Cu ions. Photoluminescence spectra show a systematic narrowing (tuning) of the band gap depending on the amount of Cu(II) doping. The advantage of the template assembly of doped ZnO nanorods is that it offers general access to doped oxide structures under moderate thermal conditions. The doping content of the host structure can be individually tuned by the stoichiometric ratio of the molecular precursor complex of the host metal oxide and the molecular precursor complex of the dopant, Di-aquo-bis[2-(methoxyimino)-propanoato]zinc(II) 1 and -copper(II) 2. Moreover, these keto-dioximato complexes are accessible for a number of transition metal and lanthanide elements, thus allowing this synthetic approach to be expanded into a variety of doped 1D metal oxide structures.

  17. 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

  18. 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

  19. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

    PubMed

    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.

  20. 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

  1. Practical approach to implementation of neural nets at the molecular level.

    PubMed

    Rambidi, N G

    1995-01-01

    Potentialities for implementing simple neural net information processing devices based on chemical and biochemical dynamic media are discussed. This approach gives an opportunity to construct efficient systems capable of performing some primitive operations important for imaging processing.

  2. A dual molecular beacon approach for fast detection of Mycobacterium tuberculosis.

    PubMed

    Yu, Chuan-Xing; Zhao, Zi-Yun; Lv, Jian-Xin; Zhu, Ling

    2013-02-01

    The main objectives of this study were to assess a dual molecular beacon approach for fast detection of Mycobacterium tuberculosis (MT). MT beacon (Tb-B) was designed to target the unique IS6110 (114 bp) and rpoB (215 bp) fragment of the MT (H37Ra) genome, and the two fragments were inserted into the PMD-19T vector after purification, by PCR and sequencing, to construct plasmids. Different dilutions of positive plasmid standards were used for dual molecular beacon RT-PCR of rpoB and IS6110, and standard curves were established.The results show that the dual molecular beacon of rpoB and IS6110 detecting MT was stable (CV is 1.91-2.68 %) with a high amplification efficiency (95.6 %). In addition, the strains of non MT did not generate fluorescence signals, while strains of MT did, indicating that the primers and molecular beacons were specific, and only MT complex was amplified. The linear range was wide (10(3)-10(11) copies/mL), and clinical specimens presenting different bacterial counts can be detected.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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).

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Sugioka, Hideyuki

    2016-09-01

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

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

    PubMed

    Song, Yu-Fei; Tsunashima, Ryo

    2012-11-21

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

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

    PubMed

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

    2014-04-21

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

  12. 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

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

    PubMed

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

    2016-03-01

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

  14. 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.

  15. Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

    SciTech Connect

    Rajagopalan, Raghavan

    2006-01-30

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

  16. 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.

  17. 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

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

    PubMed

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

    2015-01-01

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

  19. A New Approach: Competency-Based Education

    ERIC Educational Resources Information Center

    Hall, Katherine B.

    1976-01-01

    Describes competency-based education, discusses the alleged strenghts and weaknesses as presented by its supporters and critics, and points up the impact of competency-based education on the home economist, particularly the home economics educator. (TA)

  20. 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

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

    PubMed

    Müller, Klaus

    2014-01-01

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

  2. 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.

  3. 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.

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  6. 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

  7. Development of Two Molecular Approaches for Differentiation of Clinically Relevant Yeast Species Closely Related to Candida guilliermondii and Candida famata

    PubMed Central

    Feng, Xiaobo; Wu, Jingsong; Ling, Bo; Yang, Xianwei; Liao, Wanqing

    2014-01-01

    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

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

    PubMed

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

    2008-05-15

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

  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. 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…

  11. Sideline emergencies: an evidence-based approach.

    PubMed

    Fitch, R Warne; Cox, Charles L; Hannah, Gene A; Diamond, Alex B; Gregory, Andrew J M; Wilson, Kristina M

    2011-01-01

    As participation in athletics continues to increase, so too will the occurrence of on-field injuries and medical emergencies. The field of sports medicine continues to advance and many events will have on-site medical staff present. This article reviews the most catastrophic injuries and medical emergencies that are encountered in sports and presents the highest level evidence in regards to on-field approach and management of the athlete.

  12. Deciphering molecular determinants of chemotherapy in gastrointestinal malignancy using systems biology approaches.

    PubMed

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2014-09-01

    Gastrointestinal cancers are asymptomatic in early tumor development, leading to high mortality rates. Peri- or postoperative chemotherapy is a common strategy used to prolong the life expectancy of patients with these diseases. Understanding the molecular mechanisms by which anticancer drugs exert their effect is crucial to the development of anticancer therapies, especially when drug resistance occurs and an alternative drug is needed. By integrating high-throughput techniques and computational modeling to explore biological systems at different levels, from gene expressions to networks, systems biology approaches have been successfully applied in various fields of cancer research. In this review, we highlight chemotherapy studies that reveal potential signatures using microarray analysis, next-generation sequencing (NGS), proteomic and metabolomic approaches for the treatment of gastrointestinal cancers.

  13. 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

  14. 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.

  15. 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.

  16. Molecular approaches to trematode systematics: 'best practice' and implications for future study.

    PubMed

    Blasco-Costa, Isabel; Cutmore, Scott C; Miller, Terrence L; Nolan, Matthew J

    2016-03-01

    To date, morphological analysis has been the cornerstone to trematode systematics. However, since the late-1980s we have seen an increased integration of genetic data to overcome problems encountered when morphological data are considered in isolation. Here, we provide advice regarding the 'best molecular practice' for trematode taxonomy and systematic studies, in an attempt to help unify the field and provide a solid foundation to underpin future work. Emphasis is placed on defining the study goals and recommendations are made regarding sample preservation, extraction methods, and the submission of molecular vouchers. We advocate generating sequence data from all parasite species/host species/geographic location combinations and stress the importance of selecting two independently evolving loci (one ribosomal and one mitochondrial marker). We recommend that loci should be chosen to provide genetic variation suitable to address the question at hand and for which sufficient 'useful' comparative sequence data already exist. Quality control of the molecular data via using proof-reading Taq polymerase, sequencing PCR amplicons using both forward and reverse primers, ensuring that a minimum of 85% overlap exists when constructing consensus sequences, and checking electropherograms by eye is stressed. We advise that all genetic results are best interpreted using a holistic biological approach, which considers morphology, host identity, collection locality, and ecology. Finally, we consider what advances next-generation sequencing holds for trematode taxonomy and systematics. PMID:26898592

  17. 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

  18. Meiotic chromosome synapsis and recombination in Arabidopsis thaliana: new ways of integrating cytological and molecular approaches.

    PubMed

    Sanchez-Moran, E; Armstrong, S J

    2014-06-01

    Meiosis is an evolutionary conserved mechanism that produces haploid gametes and is essential for the sexual reproduction of higher eukaryotes. Since the late nineteenth century, meiosis has been studied in plants due their large chromosomes compared with other organisms and due to advances in microscopy and cytological approaches. On the other hand, non-plant model organisms like budding yeast have been widely used recently in order to characterise the molecular and functional aspects of meiosis. Arabidopsis arose as a new meiotic model for plants during the last decade of the twentieth century. This emergence was sustained by different molecular and genetic advances, mainly by completing the full genome sequence in 2000. Since then, further development of molecular technologies and the cytological methodologies to analyse the meiotic dynamics in Arabidopsis have permitted researchers to establish plant meiosis at the forefront of international research. Some key plant meiotic recombination events have been established in Arabidopsis. These advances have placed researchers into the position to transfer their knowledge from this plant meiotic model to crops and are likely to have an impact on plant breeding and the development of agriculture in future years. PMID:24941912

  19. 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

  20. Application of combined morphological-molecular approaches to the identification of planktonic protists from environmental samples.

    PubMed

    Duff, Robert Joel; Ball, Hope; Lavrentyev, Peter J

    2008-01-01

    The value of molecular databases for unicellular eukaryotic identification and phylogenetic reconstruction is predicated on the availability of sequences and accuracy of taxonomic identifications that accompany those sequences. Biased representation of sequences is due in part to the differing ability to isolate and culture various groups of protists. Techniques that allow for parallel single-cell morphological and molecular identifications have been reported for a few groups of unicellular protists. We have sought to explore how those techniques can be adapted to work across a greater phylogenetic diversity of taxa. Twelve morphologically diverse and abundant members of limnetic microplankton, including ciliates, dinoflagellates, cryptophytes, stramenopiles, and synurophytes, were targeted for analysis. These cells were captured directly from environmental samples, identified, and prepared for sequence analyses using variations of single-cell extraction techniques depending on their size, mobility, and the absence or presence of the cell wall. The application of these techniques yielded a strong congruence between the morphological and molecular identifications of the targeted taxa. Challenges to the single-cell approach in some groups are discussed. The general ability to obtain DNA sequences and morphological descriptions from individual cells should open new avenues to studying either rare or difficult to culture taxa, even directly at the point of collection (e.g. remote locations or shipboard).

  1. Molecular approaches to trematode systematics: 'best practice' and implications for future study.

    PubMed

    Blasco-Costa, Isabel; Cutmore, Scott C; Miller, Terrence L; Nolan, Matthew J

    2016-03-01

    To date, morphological analysis has been the cornerstone to trematode systematics. However, since the late-1980s we have seen an increased integration of genetic data to overcome problems encountered when morphological data are considered in isolation. Here, we provide advice regarding the 'best molecular practice' for trematode taxonomy and systematic studies, in an attempt to help unify the field and provide a solid foundation to underpin future work. Emphasis is placed on defining the study goals and recommendations are made regarding sample preservation, extraction methods, and the submission of molecular vouchers. We advocate generating sequence data from all parasite species/host species/geographic location combinations and stress the importance of selecting two independently evolving loci (one ribosomal and one mitochondrial marker). We recommend that loci should be chosen to provide genetic variation suitable to address the question at hand and for which sufficient 'useful' comparative sequence data already exist. Quality control of the molecular data via using proof-reading Taq polymerase, sequencing PCR amplicons using both forward and reverse primers, ensuring that a minimum of 85% overlap exists when constructing consensus sequences, and checking electropherograms by eye is stressed. We advise that all genetic results are best interpreted using a holistic biological approach, which considers morphology, host identity, collection locality, and ecology. Finally, we consider what advances next-generation sequencing holds for trematode taxonomy and systematics.

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

    PubMed

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

    2011-10-01

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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Eukaryotic molecular biodiversity: systematic approaches for the assessment of symbiotic associations.

    PubMed

    Hackstein, J H

    1997-07-01

    'Biodiversity' addresses the wealth of species that constitute the biosphere. Notwithstanding that they have been regarded as mental constructs in the past, species are really existing entities that form and disappear in the course of evolution. Molecular techniques allow to trace the dynamics of speciation and to determine the relatedness of species and the genetic diversity within populations. These techniques also permit to recognize the incredible diversity of protists: their importance for the global conversion of biomass and energy had been greatly underestimated until recently. Because it is not possible to 'count' all species living on earth, a variety of approaches have been used to estimate global biodiversity. Such estimations are extrapolations of historical trends or of punctual assessments of the biodiversity of selected ecosystems. Therefore, new concepts are required to calculate global biodiversity. Systematic approaches that evaluate small, complex biotopes exhaustively, or that calculate the number of symbionts or parasites on the basis of their potential hosts have already led to a substantial revision of earlier estimations. Here, an evaluation of potential animal hosts for methanogenic archaea and intestinal protists is described that reveals the importance of host taxonomy for the assessments. If molecular techniques can confirm the presumed specificity of symbiotic and parasitic associations a substantial revision of the current assumptions about the biodiversity of such organisms will be necessary.

  11. 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

  12. 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.

  13. Investigative Primary Science: A Problem-Based Learning Approach

    ERIC Educational Resources Information Center

    Etherington, Matthew B.

    2011-01-01

    This study reports on the success of using a problem-based learning approach (PBL) as a pedagogical mode of learning open inquiry science within a traditional four-year undergraduate elementary teacher education program. In 2010, a problem-based learning approach to teaching primary science replaced the traditional content driven syllabus. During…

  14. 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…

  15. 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…

  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.

  17. 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

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

    PubMed

    Watanabe, Satoshi; Harada, Kyuya; Abe, Jun

    2012-01-01

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

  19. 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

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

    1995-03-01

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