[The interpretation and integration of traditional Chinese phytotherapy into Western-type medicine with the possession of knowledge of the human genome].

PubMed

Blázovics, Anna

2018-05-01

The terminology of traditional Chinese medicine (TCM) is hardly interpretable in the context of human genome, therefore the human genome program attracted attention towards the Western practice of medicine in China. In the last two decades, several important steps could be observed in China in relation to the approach of traditional Chinese and Western medicine. The Chinese government supports the realization of information databases for research in order to clarify the molecular biology level to detect associations between gene expression signal transduction pathways and protein-protein interactions, and the effects of bioactive components of Chinese drugs and their effectiveness. The values of TCM are becoming more and more important for Western medicine as well, because molecular biological therapies did not redeem themselves, e.g., in tumor therapy. Orv Hetil. 2018; 159(18): 696-702.

Semi-Automated Curation Allows Causal Network Model Building for the Quantification of Age-Dependent Plaque Progression in ApoE-/- Mouse.

PubMed

Szostak, Justyna; Martin, Florian; Talikka, Marja; Peitsch, Manuel C; Hoeng, Julia

2016-01-01

The cellular and molecular mechanisms behind the process of atherosclerotic plaque destabilization are complex, and molecular data from aortic plaques are difficult to interpret. Biological network models may overcome these difficulties and precisely quantify the molecular mechanisms impacted during disease progression. The atherosclerosis plaque destabilization biological network model was constructed with the semiautomated curation pipeline, BELIEF. Cellular and molecular mechanisms promoting plaque destabilization or rupture were captured in the network model. Public transcriptomic data sets were used to demonstrate the specificity of the network model and to capture the different mechanisms that were impacted in ApoE -/- mouse aorta at 6 and 32 weeks. We concluded that network models combined with the network perturbation amplitude algorithm provide a sensitive, quantitative method to follow disease progression at the molecular level. This approach can be used to investigate and quantify molecular mechanisms during plaque progression.

Using yeast to determine the functional consequences of mutations in the human p53 tumor suppressor gene: An introductory course-based undergraduate research experience in molecular and cell biology.

PubMed

Hekmat-Scafe, Daria S; Brownell, Sara E; Seawell, Patricia Chandler; Malladi, Shyamala; Imam, Jamie F Conklin; Singla, Veena; Bradon, Nicole; Cyert, Martha S; Stearns, Tim

2017-03-04

The opportunity to engage in scientific research is an important, but often neglected, component of undergraduate training in biology. We describe the curriculum for an innovative, course-based undergraduate research experience (CURE) appropriate for a large, introductory cell and molecular biology laboratory class that leverages students' high level of interest in cancer. The course is highly collaborative and emphasizes the analysis and interpretation of original scientific data. During the course, students work in teams to characterize a collection of mutations in the human p53 tumor suppressor gene via expression and analysis in yeast. Initially, student pairs use both qualitative and quantitative assays to assess the ability of their p53 mutant to activate expression of reporter genes, and they localize their mutation within the p53 structure. Through facilitated discussion, students suggest possible molecular explanations for the transactivation defects displayed by their p53 mutants and propose experiments to test these hypotheses that they execute during the second part of the course. They use a western blot to determine whether mutant p53 levels are reduced, a DNA-binding assay to test whether recognition of any of three p53 target sequences is compromised, and fluorescence microscopy to assay nuclear localization. Students studying the same p53 mutant periodically convene to discuss and interpret their combined data. The course culminates in a poster session during which students present their findings to peers, instructors, and the greater biosciences community. Based on our experience, we provide recommendations for the development of similar large introductory lab courses. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):161-178, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

Modeling molecular mechanisms in the axon

NASA Astrophysics Data System (ADS)

de Rooij, R.; Miller, K. E.; Kuhl, E.

2017-03-01

Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena—both in isolation and in interaction—to explore emergent cellular-level features under physiological and pathological conditions.

Structural Interpretation of the Large Slowdown of Water Dynamics at Stacked Phospholipid Membranes for Decreasing Hydration Level: All-Atom Molecular Dynamics

DOE PAGES

Calero, Carles; Stanley, H.; Franzese, Giancarlo

2016-04-27

Hydration water determines the stability and function of phospholipid membranes as well as the interaction of membranes with other molecules. Experiments and simulations have shown that water dynamics slows down dramatically as the hydration decreases, suggesting that the interfacial water that dominates the average dynamics at low hydration is slower than water away from the membrane. Here, based on all-atom molecular dynamics simulations, we provide an interpretation of the slowdown of interfacial water in terms of the structure and dynamics of water–water and water–lipid hydrogen bonds (HBs). We calculate the rotational and translational slowdown of the dynamics of water confinedmore » in stacked phospholipid membranes at different levels of hydration, from completely hydrated to poorly hydrated membranes. For all hydrations, we analyze the distribution of HBs and find that water–lipids HBs last longer than water–water HBs and that at low hydration most of the water is in the interior of the membrane. We also show that water–water HBs become more persistent as the hydration is lowered. We attribute this effect (i) to HBs between water molecules that form, in turn, persistent HBs with lipids; (ii) to the hindering of the H-bonding switching between water molecules due to the lower water density at the interface; and (iii) to the higher probability of water–lipid HBs as the hydration decreases. Lastly, our interpretation of the large dynamic slowdown in water under dehydration is potentially relevant in understanding membrane biophysics at different hydration levels.« less

Impact of anisotropy on the structure and dynamics of ionic liquids: A computational study of 1-butyl-3-methyl-imidazolium trifluoroacetate

NASA Astrophysics Data System (ADS)

Schröder, C.; Rudas, T.; Neumayr, G.; Gansterer, W.; Steinhauser, O.

2007-07-01

The complex ionic network of 1-butyl-3-methyl-imidazolium trifluoroacetate was simulated by means of the molecular dynamics methods over a time period of 100ns. The influence of the anisotropy of the shape and charge distribution of both the cations and the anions on the local (molecular) and global (collective) structure and dynamics is analyzed. The distance-dependent g coefficients of the orientational probability function g(r,Ω) were found to be an excellent way to interpret local structure. Thereby, the combination and interrelation of individual g coefficients elucidate the mutual orientation. Dynamics at the molecular level is characterized by the time correlation function of the center-of-mass corrected molecular dipole moment μcm. Upon uniting the set of molecular dipoles to a single collective rotational dipole moment, MD, dynamics on a global level is studied. Decomposing into subsets of cations and anions respective self terms as well as the prominent cross term can be extracted. This decomposition also enables a detailed peak assignment in dielectric spectra.

Impact of anisotropy on the structure and dynamics of ionic liquids: a computational study of 1-butyl-3-methyl-imidazolium trifluoroacetate.

PubMed

Schröder, C; Rudas, T; Neumayr, G; Gansterer, W; Steinhauser, O

2007-07-28

The complex ionic network of 1-butyl-3-methyl-imidazolium trifluoroacetate was simulated by means of the molecular dynamics methods over a time period of 100 ns. The influence of the anisotropy of the shape and charge distribution of both the cations and the anions on the local (molecular) and global (collective) structure and dynamics is analyzed. The distance-dependent g coefficients of the orientational probability function g(r,Omega) were found to be an excellent way to interpret local structure. Thereby, the combination and interrelation of individual g coefficients elucidate the mutual orientation. Dynamics at the molecular level is characterized by the time correlation function of the center-of-mass corrected molecular dipole moment mucm. Upon uniting the set of molecular dipoles to a single collective rotational dipole moment, MD, dynamics on a global level is studied. Decomposing into subsets of cations and anions respective self terms as well as the prominent cross term can be extracted. This decomposition also enables a detailed peak assignment in dielectric spectra.

Method Designed to Respect Molecular Heterogeneity Can Profoundly Correct Present Data Interpretations for Genome-Wide Expression Analysis

PubMed Central

Chen, Chih-Hao; Hsu, Chueh-Lin; Huang, Shih-Hao; Chen, Shih-Yuan; Hung, Yi-Lin; Chen, Hsiao-Rong; Wu, Yu-Chung

2015-01-01

Although genome-wide expression analysis has become a routine tool for gaining insight into molecular mechanisms, extraction of information remains a major challenge. It has been unclear why standard statistical methods, such as the t-test and ANOVA, often lead to low levels of reproducibility, how likely applying fold-change cutoffs to enhance reproducibility is to miss key signals, and how adversely using such methods has affected data interpretations. We broadly examined expression data to investigate the reproducibility problem and discovered that molecular heterogeneity, a biological property of genetically different samples, has been improperly handled by the statistical methods. Here we give a mathematical description of the discovery and report the development of a statistical method, named HTA, for better handling molecular heterogeneity. We broadly demonstrate the improved sensitivity and specificity of HTA over the conventional methods and show that using fold-change cutoffs has lost much information. We illustrate the especial usefulness of HTA for heterogeneous diseases, by applying it to existing data sets of schizophrenia, bipolar disorder and Parkinson’s disease, and show it can abundantly and reproducibly uncover disease signatures not previously detectable. Based on 156 biological data sets, we estimate that the methodological issue has affected over 96% of expression studies and that HTA can profoundly correct 86% of the affected data interpretations. The methodological advancement can better facilitate systems understandings of biological processes, render biological inferences that are more reliable than they have hitherto been and engender translational medical applications, such as identifying diagnostic biomarkers and drug prediction, which are more robust. PMID:25793610

Molecular Origin of the Vibrational Structure of Ice Ih.

PubMed

Moberg, Daniel R; Straight, Shelby C; Knight, Christopher; Paesani, Francesco

2017-06-15

An unambiguous assignment of the vibrational spectra of ice I h remains a matter of debate. This study demonstrates that an accurate representation of many-body interactions between water molecules, combined with an explicit treatment of nuclear quantum effects through many-body molecular dynamics (MB-MD), leads to a unified interpretation of the vibrational spectra of ice I h in terms of the structure and dynamics of the underlying hydrogen-bond network. All features of the infrared and Raman spectra in the OH stretching region can be unambiguously assigned by taking into account both the symmetry and the delocalized nature of the lattice vibrations as well as the local electrostatic environment experienced by each water molecule within the crystal. The high level of agreement with experiment raises prospects for predictive MB-MD simulations that, complementing analogous measurements, will provide molecular-level insights into fundamental processes taking place in bulk ice and on ice surfaces under different thermodynamic conditions.

Molecular genetic testing for cystic fibrosis: laboratory performance on the College of American Pathologists external proficiency surveys.

PubMed

Lyon, Elaine; Schrijver, Iris; Weck, Karen E; Ferreira-Gonzalez, Andrea; Richards, C Sue; Palomaki, Glenn E

2015-03-01

Molecular testing for cystic fibrosis mutations is widespread and routine in reproductive decision making and diagnosis. Our objective was to assess the level of performance of laboratories for this test. The College of American Pathologists administers external proficiency testing with multiple DNA samples distributed biannually. RESULTS are analyzed, reviewed, and graded by the joint College of American Pathologists/American College of Medical Genetics and Genomics Biochemical and Molecular Genetics Committee. Assessment is based on genotype and associated clinical interpretation. Overall, 357 clinical laboratories participated in the proficiency testing survey between 2003 and 2013 (322 in the United States and 35 international). In 2013, US participants reported performing nearly 120,000 tests monthly. Analytical sensitivity and specificity of US laboratories were 98.8% (95% confidence interval: 98.4-99.1%) and 99.6% (95% confidence interval: 99.4-99.7%), respectively. Analytical sensitivity improved between 2003 and 2008 (from 97.9 to 99.3%; P = 0.007) and remained steady thereafter. Clinical interpretation matched the intended response for 98.8, 86.0, and 91.0% of challenges with no, one, or two mutations, respectively. International laboratories performed similarly. Laboratory testing for cystic fibrosis in the United States has improved since 2003, and these data demonstrate a high level of quality. Neither the number of samples tested nor test methodology affected performance.

Let's get honest about sampling.

PubMed

Mobley, David L

2012-01-01

Molecular simulations see widespread and increasing use in computation and molecular design, especially within the area of molecular simulations applied to biomolecular binding and interactions, our focus here. However, force field accuracy remains a concern for many practitioners, and it is often not clear what level of accuracy is really needed for payoffs in a discovery setting. Here, I argue that despite limitations of today's force fields, current simulation tools and force fields now provide the potential for real benefits in a variety of applications. However, these same tools also provide irreproducible results which are often poorly interpreted. Continued progress in the field requires more honesty in assessment and care in evaluation of simulation results, especially with respect to convergence.

Decoding molecular interactions in microbial communities

PubMed Central

Abreu, Nicole A.; Taga, Michiko E.

2016-01-01

Microbial communities govern numerous fundamental processes on earth. Discovering and tracking molecular interactions among microbes is critical for understanding how single species and complex communities impact their associated host or natural environment. While recent technological developments in DNA sequencing and functional imaging have led to new and deeper levels of understanding, we are limited now by our inability to predict and interpret the intricate relationships and interspecies dependencies within these communities. In this review, we highlight the multifaceted approaches investigators have taken within their areas of research to decode interspecies molecular interactions that occur between microbes. Understanding these principles can give us greater insight into ecological interactions in natural environments and within synthetic consortia. PMID:27417261

Differences in the molecular biology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third.

PubMed

Lehmann, Kuno; Schneider, Paul M

2010-01-01

Adenocarcinoma of the distal esophagus, gastric cardia, and upper gastric third are grouped in type I-III by the Siewert classification. This classification is based on the endoscopic localisation of the tumor center, and is the most important diagnostic tool to group these tumors. On a molecular level, there is currently no marker that would allow to differentiate the three different types. Furthermore, the Siewert classification was not uniformly used in the recent literature, making interpretation and generalization of these results difficult. However, several potential targets have been identified that may help to separate these tumors by molecular markers, and are summarized in this chapter.

New physicochemical interpretations for the adsorption of food dyes on chitosan films using statistical physics treatment.

PubMed

Dotto, G L; Pinto, L A A; Hachicha, M A; Knani, S

2015-03-15

In this work, statistical physics treatment was employed to study the adsorption of food dyes onto chitosan films, in order to obtain new physicochemical interpretations at molecular level. Experimental equilibrium curves were obtained for the adsorption of four dyes (FD&C red 2, FD&C yellow 5, FD&C blue 2, Acid Red 51) at different temperatures (298, 313 and 328 K). A statistical physics formula was used to interpret these curves, and the parameters such as, number of adsorbed dye molecules per site (n), anchorage number (n'), receptor sites density (NM), adsorbed quantity at saturation (N asat), steric hindrance (τ), concentration at half saturation (c1/2) and molar adsorption energy (ΔE(a)) were estimated. The relation of the above mentioned parameters with the chemical structure of the dyes and temperature was evaluated and interpreted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Counterion adsorption theory of dilute polyelectrolyte solutions: Apparent molecular weight, second virial coefficient, and intermolecular structure factor

PubMed Central

Muthukumar, M.

2012-01-01

Polyelectrolyte chains are well known to be strongly correlated even in extremely dilute solutions in the absence of additional strong electrolytes. Such correlations result in severe difficulties in interpreting light scattering measurements in the determination of the molecular weight, radius of gyration, and the second virial coefficient of charged macromolecules at lower ionic strengths from added strong electrolytes. By accounting for charge-regularization of the polyelectrolyte by the counterions, we present a theory of the apparent molecular weight, second virial coefficient, and the intermolecular structure factor in dilute polyelectrolyte solutions in terms of concentrations of the polymer and the added strong electrolyte. The counterion adsorption of the polyelectrolyte chains to differing levels at different concentrations of the strong electrolyte can lead to even an order of magnitude discrepancy in the molecular weight inferred from light scattering measurements. Based on counterion-mediated charge regularization, the second virial coefficient of the polyelectrolyte and the interchain structure factor are derived self-consistently. The effect of the interchain correlations, dominating at lower salt concentrations, on the inference of the radius of gyration and on molecular weight is derived. Conditions for the onset of nonmonotonic scattering wave vector dependence of scattered intensity upon lowering the electrolyte concentration and interpretation of the apparent radius of gyration are derived in terms of the counterion adsorption mechanism. PMID:22830728

Electron impact ionization dynamics of para-benzoquinone

NASA Astrophysics Data System (ADS)

Jones, D. B.; Ali, E.; Ning, C. G.; Colgan, J.; Ingólfsson, O.; Madison, D. H.; Brunger, M. J.

2016-10-01

Triple differential cross sections (TDCSs) for the electron impact ionization of the unresolved combination of the 4 highest occupied molecular orbitals (4b3g, 5b2u, 1b1g, and 2b3u) of para-benzoquinone are reported. These were obtained in an asymmetric coplanar geometry with the scattered electron being observed at the angles -7.5°, -10.0°, -12.5° and -15.0°. The experimental cross sections are compared to theoretical calculations performed at the molecular 3-body distorted wave level, with a marginal level of agreement between them being found. The character of the ionized orbitals, through calculated momentum profiles, provides some qualitative interpretation for the measured angular distributions of the TDCS.

Polymer-surfactant complex formation and its effect on turbulent wall shear stress.

PubMed

Suksamranchit, Siriluck; Sirivat, Anuvat; Jamieson, Alexander M

2006-02-01

Turbulent drag reduction in Couette flow was investigated in terms of a decrease in wall shear stress for aqueous solutions of a nonionic polymer, poly(ethylene oxide) (PEO), a cationic surfactant, hexadecyltrimethylammonium chloride (HTAC), and their mixtures. Consistent with literature data, drag reduction was observed for PEO solutions above a critical molecular weight, 0.91 x 10(5) < Mc < 3.04 x 10(5) g/mol. Maximum drag reduction occurred at an optimum concentration, c(PEO)*, which scales inversely with molecular weight, and the % maximum drag reduction increases with molecular weight. For aqueous HTAC solutions, wall shear stress decreased with increasing HTAC concentration and leveled off at an optimum concentration, c(HTAC)*, comparable to the critical micelle concentration. For HTAC/PEO mixtures, the critical PEO molecular weight for drag reduction decreases, interpreted as due to an increase in hydrodynamic volume because of binding of HTAC micelles to PEO. Consistent with this interpretation, at fixed PEO concentration, maximum drag reduction was observed at an optimum HTAC concentration, c(HTAC/PEO)*, comparable to the maximum binding concentration, MBC. Also, with HTAC concentration fixed at the MBC, the optimum PEO concentration for drag reduction, c(PEO/HTAC)*, decreases relative to that, c(PEO)*, in the absence of HTAC.

Spectroscopic (FT-IR, FT-Raman, NMR and UV-Visible) and quantum chemical studies of molecular geometry, Frontier molecular orbital, NLO, NBO and thermodynamic properties of salicylic acid.

PubMed

Suresh, S; Gunasekaran, S; Srinivasan, S

2014-11-11

The solid phase FT-IR and FT-Raman spectra of 2-hydroxybenzoic acid (salicylic acid) have been recorded in the region 4000-400 and 4000-100 cm(-1) respectively. The optimized molecular geometry and fundamental vibrational frequencies are interpreted with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) method and a comparative study between Hartree Fork (HF) method at 6-311++G(d,p) level basis set. The calculated harmonic vibrational frequencies are scaled and they are compared with experimentally obtained FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated potential energy distribution (PED). The time dependent DFT method is employed to predict its absorption energy and oscillator strength. The linear polarizability (α) and the first order hyper polarizability (β) values of the investigated molecule have been computed. The electronic properties, such as HOMO and LUMO energies, molecular electrostatic potential (MEP) are also performed. Stability of the molecule arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Published by Elsevier B.V.

[Research progress on the cloning of Mendel's gene in pea (Pisum sativum L.) and its application in genetics teaching].

PubMed

He, Feng-Hua; Zhu, Bi-Yan; Gao, Feng; Li, Shao-Shan; Li, Niang-Hui

2013-07-01

One hundred and fifty years ago, Gregor Mendel investigated the segregation of seven traits in pea (Pisum sativum) and established the law of segregation and the law of independent assortment in genetics. After the two laws of genetics were rediscovered in 1900, the seven traits have been extensively investigated in the fields of plant physiology and biochemistry as well as in the cell and molecular levels. Recently, with the development of molecular technology in genetics, four genes for seed shape (R), stem length (Le), cotyledon colour (I), and flower colour (A) have been cloned and sequenced; and another three genes for immature pod colour (Gp), fasciation (Fa) and pod form (V) have been located in the linkage groups, respectively. The identification and cloning of the four Mendel's genes will help deeply understand the basic concept of gene in many respects: like the diversity of gene function, the different origins for gene mutation in molecular level, and the molecular nature of a dominant gene or a recessive gene. In teaching of genetics, the introduction of most recent research advancements of cloning of Mendel's genes to the students and the interpretation of the Mendel's laws in molecular level will help students promote their learning interests in genetics and help students grasp the whole content from classical genetics to molecular genetics and the developmental direction of this subject.

Applications of isothermal titration calorimetry - the research and technical developments from 2011 to 2015.

PubMed

Falconer, Robert J

2016-10-01

Isothermal titration calorimetry is a widely used biophysical technique for studying the formation or dissociation of molecular complexes. Over the last 5 years, much work has been published on the interpretation of isothermal titration calorimetry (ITC) data for single binding and multiple binding sites. As over 80% of ITC papers are on macromolecules of biological origin, this interpretation is challenging. Some researchers have attempted to link the thermodynamics constants to events at the molecular level. This review highlights work carried out using binding sites characterized using x-ray crystallography techniques that allow speculation about individual bond formation and the displacement of individual water molecules during ligand binding and link these events to the thermodynamic constants for binding. The review also considers research conducted with synthetic binding partners where specific binding events like anion-π and π-π interactions were studied. The revival of assays that enable both thermodynamic and kinetic information to be collected from ITC data is highlighted. Lastly, published criticism of ITC research from a physical chemistry perspective is appraised and practical advice provided for researchers unfamiliar with thermodynamics and its interpretation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

NO/redox disequilibrium in the failing heart and cardiovascular system

PubMed Central

Hare, Joshua M.; Stamler, Jonathan S.

2005-01-01

There is growing evidence that the altered production and/or spatiotemporal distribution of reactive oxygen and nitrogen species creates oxidative and/or nitrosative stresses in the failing heart and vascular tree, which contribute to the abnormal cardiac and vascular phenotypes that characterize the failing cardiovascular system. These derangements at the integrated system level can be interpreted at the cellular and molecular levels in terms of adverse effects on signaling elements in the heart, vasculature, and blood that subserve cardiac and vascular homeostasis. PMID:15765132

Submicron particulate organic matter in the urban atmosphere: a new method for real-time measurement, molecular-level characterization and source apportionment

NASA Astrophysics Data System (ADS)

Müller, Markus; Eichler, Philipp; D'Anna, Barbara; Tan, Wen; Wisthaler, Armin

2017-04-01

We used a novel chemical analytical method for measuring submicron particulate organic matter in the atmosphere of three European cities (Innsbruck, Lyon, Valencia). Proton-Transfer-Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) was used in combination with the "chemical analysis of aerosol online" (CHARON) inlet for detecting particulate organic compounds on-line (i.e. without filter pre-collection), in real-time (1-min time resolution), at ng m-3 concentrations, with molecular-level resolution (i.e. obtaining molecular weight and elemental composition information). The CHARON-PTR-ToF-MS system monitored molecular tracers associated with different particle sources including levoglucosan from biomass combustion, PAHs from vehicular traffic, nicotine from cigarette smoking, and monoterpene oxidation products secondarily formed from biogenic emissions. The tracer information was used for interpreting positive matrix factorization (PMF) data which allowed us to apportion the sources of submicron particulate organic matter in the different urban environments. This work was funded through the PIMMS ITN, which was supported by the European Commission's 7th Framework Programme under grant agreement number 287382.

Molecular Dissection of a Major Gene Effect on a Quantitative Trait: The Level of Alcohol Dehydrogenase Expression in Drosophila Melanogaster

PubMed Central

Stam, L. F.; Laurie, C. C.

1996-01-01

A molecular mapping experiment shows that a major gene effect on a quantitative trait, the level of alcohol dehydrogenase expression in Drosophila melanogaster, is due to multiple polymorphisms within the Adh gene. These polymorphisms are located in an intron, the coding sequence, and the 3' untranslated region. Because of nonrandom associations among polymorphisms at different sites, the individual effects combine (in some cases epistatically) to produce ``superalleles'' with large effect. These results have implications for the interpretation of major gene effects detected by quantitative trait locus mapping methods. They show that large effects due to a single locus may be due to multiple associated polymorphisms (or sequential fixations in isolated populations) rather than individual mutations of large effect. PMID:8978044

Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans.

PubMed

Pyle, Angela; Hudson, Gavin; Wilson, Ian J; Coxhead, Jonathan; Smertenko, Tania; Herbert, Mary; Santibanez-Koref, Mauro; Chinnery, Patrick F

2015-05-01

Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level, inferring a paternal source for the mixed haplotypes. However, interpreting these data is fraught with difficulty, and direct experimental evidence is lacking. Using extreme-high depth mtDNA re-sequencing up to ~1.2 million-fold coverage, we find no evidence that paternal mtDNA haplotypes are transmitted to offspring in humans, thus excluding a simple dilution mechanism for uniparental transmission of mtDNA present in all healthy individuals. Our findings indicate that an active mechanism eliminates paternal mtDNA which likely acts at the molecular level.

Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans

PubMed Central

Pyle, Angela; Hudson, Gavin; Wilson, Ian J.; Coxhead, Jonathan; Smertenko, Tania; Herbert, Mary; Santibanez-Koref, Mauro; Chinnery, Patrick F.

2015-01-01

Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level, inferring a paternal source for the mixed haplotypes. However, interpreting these data is fraught with difficulty, and direct experimental evidence is lacking. Using extreme-high depth mtDNA re-sequencing up to ~1.2 million-fold coverage, we find no evidence that paternal mtDNA haplotypes are transmitted to offspring in humans, thus excluding a simple dilution mechanism for uniparental transmission of mtDNA present in all healthy individuals. Our findings indicate that an active mechanism eliminates paternal mtDNA which likely acts at the molecular level. PMID:25973765

Using yeast to determine the functional consequences of mutations in the human p53 tumor suppressor gene: An introductory course‐based undergraduate research experience in molecular and cell biology

PubMed Central

Brownell, Sara E.; Seawell, Patricia Chandler; Malladi, Shyamala; Imam, Jamie F. Conklin; Singla, Veena; Bradon, Nicole; Cyert, Martha S.; Stearns, Tim

2016-01-01

Abstract The opportunity to engage in scientific research is an important, but often neglected, component of undergraduate training in biology. We describe the curriculum for an innovative, course‐based undergraduate research experience (CURE) appropriate for a large, introductory cell and molecular biology laboratory class that leverages students′ high level of interest in cancer. The course is highly collaborative and emphasizes the analysis and interpretation of original scientific data. During the course, students work in teams to characterize a collection of mutations in the human p53 tumor suppressor gene via expression and analysis in yeast. Initially, student pairs use both qualitative and quantitative assays to assess the ability of their p53 mutant to activate expression of reporter genes, and they localize their mutation within the p53 structure. Through facilitated discussion, students suggest possible molecular explanations for the transactivation defects displayed by their p53 mutants and propose experiments to test these hypotheses that they execute during the second part of the course. They use a western blot to determine whether mutant p53 levels are reduced, a DNA‐binding assay to test whether recognition of any of three p53 target sequences is compromised, and fluorescence microscopy to assay nuclear localization. Students studying the same p53 mutant periodically convene to discuss and interpret their combined data. The course culminates in a poster session during which students present their findings to peers, instructors, and the greater biosciences community. Based on our experience, we provide recommendations for the development of similar large introductory lab courses. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):161–178, 2017. PMID:27873457

BioPAX – A community standard for pathway data sharing

PubMed Central

Demir, Emek; Cary, Michael P.; Paley, Suzanne; Fukuda, Ken; Lemer, Christian; Vastrik, Imre; Wu, Guanming; D’Eustachio, Peter; Schaefer, Carl; Luciano, Joanne; Schacherer, Frank; Martinez-Flores, Irma; Hu, Zhenjun; Jimenez-Jacinto, Veronica; Joshi-Tope, Geeta; Kandasamy, Kumaran; Lopez-Fuentes, Alejandra C.; Mi, Huaiyu; Pichler, Elgar; Rodchenkov, Igor; Splendiani, Andrea; Tkachev, Sasha; Zucker, Jeremy; Gopinath, Gopal; Rajasimha, Harsha; Ramakrishnan, Ranjani; Shah, Imran; Syed, Mustafa; Anwar, Nadia; Babur, Ozgun; Blinov, Michael; Brauner, Erik; Corwin, Dan; Donaldson, Sylva; Gibbons, Frank; Goldberg, Robert; Hornbeck, Peter; Luna, Augustin; Murray-Rust, Peter; Neumann, Eric; Reubenacker, Oliver; Samwald, Matthias; van Iersel, Martijn; Wimalaratne, Sarala; Allen, Keith; Braun, Burk; Whirl-Carrillo, Michelle; Dahlquist, Kam; Finney, Andrew; Gillespie, Marc; Glass, Elizabeth; Gong, Li; Haw, Robin; Honig, Michael; Hubaut, Olivier; Kane, David; Krupa, Shiva; Kutmon, Martina; Leonard, Julie; Marks, Debbie; Merberg, David; Petri, Victoria; Pico, Alex; Ravenscroft, Dean; Ren, Liya; Shah, Nigam; Sunshine, Margot; Tang, Rebecca; Whaley, Ryan; Letovksy, Stan; Buetow, Kenneth H.; Rzhetsky, Andrey; Schachter, Vincent; Sobral, Bruno S.; Dogrusoz, Ugur; McWeeney, Shannon; Aladjem, Mirit; Birney, Ewan; Collado-Vides, Julio; Goto, Susumu; Hucka, Michael; Le Novère, Nicolas; Maltsev, Natalia; Pandey, Akhilesh; Thomas, Paul; Wingender, Edgar; Karp, Peter D.; Sander, Chris; Bader, Gary D.

2010-01-01

BioPAX (Biological Pathway Exchange) is a standard language to represent biological pathways at the molecular and cellular level. Its major use is to facilitate the exchange of pathway data (http://www.biopax.org). Pathway data captures our understanding of biological processes, but its rapid growth necessitates development of databases and computational tools to aid interpretation. However, the current fragmentation of pathway information across many databases with incompatible formats presents barriers to its effective use. BioPAX solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. BioPAX was created through a community process. Through BioPAX, millions of interactions organized into thousands of pathways across many organisms, from a growing number of sources, are available. Thus, large amounts of pathway data are available in a computable form to support visualization, analysis and biological discovery. PMID:20829833

Exploratory factor analysis of pathway copy number data with an application towards the integration with gene expression data.

PubMed

van Wieringen, Wessel N; van de Wiel, Mark A

2011-05-01

Realizing that genes often operate together, studies into the molecular biology of cancer shift focus from individual genes to pathways. In order to understand the regulatory mechanisms of a pathway, one must study its genes at all molecular levels. To facilitate such study at the genomic level, we developed exploratory factor analysis for the characterization of the variability of a pathway's copy number data. A latent variable model that describes the call probability data of a pathway is introduced and fitted with an EM algorithm. In two breast cancer data sets, it is shown that the first two latent variables of GO nodes, which inherit a clear interpretation from the call probabilities, are often related to the proportion of aberrations and a contrast of the probabilities of a loss and of a gain. Linking the latent variables to the node's gene expression data suggests that they capture the "global" effect of genomic aberrations on these transcript levels. In all, the proposed method provides an possibly insightful characterization of pathway copy number data, which may be fruitfully exploited to study the interaction between the pathway's DNA copy number aberrations and data from other molecular levels like gene expression.

‘N-of-1-pathways’ unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: towards precision medicine

PubMed Central

Gardeux, Vincent; Achour, Ikbel; Li, Jianrong; Maienschein-Cline, Mark; Li, Haiquan; Pesce, Lorenzo; Parinandi, Gurunadh; Bahroos, Neil; Winn, Robert; Foster, Ian; Garcia, Joe G N; Lussier, Yves A

2014-01-01

Background The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. Indeed, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. Method ‘N-of-1-pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity between genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1-pathways predicts the deregulated pathways of each patient. Results Cross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03). Conclusions The N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies. Software http://lussierlab.org/publications/N-of-1-pathways PMID:25301808

‘N-of-1- pathways ’ unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: Towards precision medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardeux, Vincent; Achour, Ikbel; Li, Jianrong

Background: The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. This research entails, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. Method: ‘N-of-1- pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity betweenmore » genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1- pathways predicts the deregulated pathways of each patient. Results: Cross-patient N-of-1- pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03). Conclusions: The N-of-1- pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies.« less

‘N-of-1- pathways ’ unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: Towards precision medicine

DOE PAGES

Gardeux, Vincent; Achour, Ikbel; Li, Jianrong; ...

2014-11-01

Background: The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. This research entails, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. Method: ‘N-of-1- pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity betweenmore » genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1- pathways predicts the deregulated pathways of each patient. Results: Cross-patient N-of-1- pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03). Conclusions: The N-of-1- pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies.« less

Cascading network failure across the Alzheimer’s disease spectrum

PubMed Central

Knopman, David S.; Gunter, Jeffrey L.; Graff-Radford, Jonathan; Vemuri, Prashanthi; Boeve, Bradley F.; Petersen, Ronald C.; Weiner, Michael W.; Jack, Clifford R.

2016-01-01

Abstract Complex biological systems are organized across various spatiotemporal scales with particular scientific disciplines dedicated to the study of each scale (e.g. genetics, molecular biology and cognitive neuroscience). When considering disease pathophysiology, one must contemplate the scale at which the disease process is being observed and how these processes impact other levels of organization. Historically Alzheimer’s disease has been viewed as a disease of abnormally aggregated proteins by pathologists and molecular biologists and a disease of clinical symptoms by neurologists and psychologists. Bridging the divide between these scales has been elusive, but the study of brain networks appears to be a pivotal inroad to accomplish this task. In this study, we were guided by an emerging systems-based conceptualization of Alzheimer’s disease and investigated changes in brain networks across the disease spectrum. The default mode network has distinct subsystems with unique functional-anatomic connectivity, cognitive associations, and responses to Alzheimer’s pathophysiology. These distinctions provide a window into the systems-level pathophysiology of Alzheimer’s disease. Using clinical phenotyping, metadata, and multimodal neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative, we characterized the pattern of default mode network subsystem connectivity changes across the entire disease spectrum (n = 128). The two main findings of this paper are (i) the posterior default mode network fails before measurable amyloid plaques and appears to initiate a connectivity cascade that continues throughout the disease spectrum; and (ii) high connectivity between the posterior default mode network and hubs of high connectivity (many located in the frontal lobe) is associated with amyloid accumulation. These findings support a system model best characterized by a cascading network failure—analogous to cascading failures seen in power grids triggered by local overloads proliferating to downstream nodes eventually leading to widespread power outages, or systems failures. The failure begins in the posterior default mode network, which then shifts processing burden to other systems containing prominent connectivity hubs. This model predicts a connectivity ‘overload’ that precedes structural and functional declines and recasts the interpretation of high connectivity from that of a positive compensatory phenomenon to that of a load-shifting process transiently serving a compensatory role. It is unknown whether this systems-level pathophysiology is the inciting event driving downstream molecular events related to synaptic activity embedded in these systems. Possible interpretations include that the molecular-level events drive the network failure, a pathological interaction between the network-level and the molecular-level, or other upstream factors are driving both. PMID:26586695

Molecular origin of the vibrational structure of ice I h

DOE PAGES

Moberg, Daniel R.; Straight, Shelby C.; Knight, Christopher; ...

2017-05-25

Here, an unambiguous assignment of the vibrational spectra of ice I h remains a matter of debate. This study demonstrates that an accurate representation of many-body interactions between water molecules, combined with an explicit treatment of nuclear quantum effects through many-body molecular dynamics (MB-MD), leads to a unified interpretation of the vibrational spectra of ice I h in terms of the structure and dynamics of the underlying hydrogen-bond network. All features of the infrared and Raman spectra in the OH stretching region can be unambiguously assigned by taking into account both the symmetry and the delocalized nature of the latticemore » vibrations as well as the local electrostatic environment experienced by each water molecule within the crystal. The high level of agreement with experiment raises prospects for predictive MB-MD simulations that, complementing analogous measurements, will provide molecular-level insights into fundamental processes taking place in bulk ice and on ice surfaces under different thermodynamic conditions.« less

Toward Molecular Level of the “Salmonella-Victim” Ecology, Genetics, and Evolution

PubMed Central

Rumyantsev, S.N.

2004-01-01

Bacteria of the Salmonella genus are polypathogenic agents that can affect both men and animals, causing devastating and fatal illness. Despite considerable immunological, epidemiological, and genetic efforts, and increased understanding of how the Salmonella infection develops, many key questions concerning Salmonella infection remain unanswered. Salmonella can be carried as harmless commensals in some sectors of the population. In some individuals, however, the same microbes cause illness while others display immunity to primary Salmonella infection. Nothing is known about the molecular base of the Salmonella pathogenicity. Even the ability of Salmonella to destroy the victims cells has been the subject of century-long discussions. In this article, some key findings concerning ecology, molecular ecology, and cell level of the Salmonella infection genetics are summarized and interpreted from the viewpoint of evolutionary theory with certitude that this approach can help to decipher the undiscovered secrets of Salmonella infections epidemiology and pathogenesis, as well as the clinical course and severity, and to select ways for fighting against Salmonella. PMID:15105959

Towards a molecular interpretation of astringency: synthesis, 3D structure, colloidal state, and human saliva protein recognition of procyanidins.

PubMed

Cala, Olivier; Fabre, Sandy; Pinaud, Noël; Dufourc, Erick J; Fouquet, Eric; Laguerre, Michel; Pianet, Isabelle

2011-07-01

Astringency is a sensation in the mouth used in judging the quality of red wine. The rough, dry, and puckering sensation called astringency is the result of an interaction between tannins and saliva proteins, mainly proline-rich proteins (PRP), which leads to the formation and precipitation of a complex. A dry and rough sensation is then perceived in the mouth. To get an insight into astringency at the molecular level we investigated: (i) An efficient and iterative method for 4-8 procyanidin synthesis, which gives rise to all possible 4-8 procyanidins up to the tetramer with total control of degree of oligomerization and stereochemistry. (ii) The 3D-structural preferences, which take into account their internal movements, using 2D NMR and molecular modeling. (iii) The self-association process in water or hydroalcoholic solutions using diffusion NMR spectroscopy that gives the active proportion of tannins able to fix proteins. (iv) A comprehensive description of the PRP-procyanidin complex formation to get information about stoichiometry, binding site localization, and affinity constants for different procyanidins. The data collected suggest that the interactions are controlled by both procyanidin conformational and colloidal state preferences. All these results provide new insights into the molecular interpretation of tannin astringency. © Georg Thieme Verlag KG Stuttgart · New York.

Quantum mechanical calculations related to ionization and charge transfer in DNA

NASA Astrophysics Data System (ADS)

Cauët, E.; Valiev, M.; Weare, J. H.; Liévin, J.

2012-07-01

Ionization and charge migration in DNA play crucial roles in mechanisms of DNA damage caused by ionizing radiation, oxidizing agents and photo-irradiation. Therefore, an evaluation of the ionization properties of the DNA bases is central to the full interpretation and understanding of the elementary reactive processes that occur at the molecular level during the initial exposure and afterwards. Ab initio quantum mechanical (QM) methods have been successful in providing highly accurate evaluations of key parameters, such as ionization energies (IE) of DNA bases. Hence, in this study, we performed high-level QM calculations to characterize the molecular energy levels and potential energy surfaces, which shed light on ionization and charge migration between DNA bases. In particular, we examined the IEs of guanine, the most easily oxidized base, isolated and embedded in base clusters, and investigated the mechanism of charge migration over two and three stacked guanines. The IE of guanine in the human telomere sequence has also been evaluated. We report a simple molecular orbital analysis to explain how modifications in the base sequence are expected to change the efficiency of the sequence as a hole trap. Finally, the application of a hybrid approach combining quantum mechanics with molecular mechanics brings an interesting discussion as to how the native aqueous DNA environment affects the IE threshold of nucleobases.

Molecular dynamics simulation of unsaturated lipid bilayers at low hydration: parameterization and comparison with diffraction studies.

PubMed Central

Feller, S E; Yin, D; Pastor, R W; MacKerell, A D

1997-01-01

A potential energy function for unsaturated hydrocarbons is proposed and is shown to agree well with experiment, using molecular dynamics simulations of a water/octene interface and a dioleoyl phosphatidylcholine (DOPC) bilayer. The simulation results verify most of the assumptions used in interpreting the DOPC experiments, but suggest a few that should be reconsidered. Comparisons with recent results of a simulation of a dipalmitoyl phosphatidylcholine (DPPC) lipid bilayer show that disorder is comparable, even though the temperature, hydration level, and surface area/lipid for DOPC are lower. These observations highlight the dramatic effects of unsaturation on bilayer structure. Images FIGURE 3 PMID:9370424

Are we closer to the vision? A proposed framework for incorporating omics into environmental assessments.

PubMed

Martyniuk, Christopher J

2018-04-01

Environmental science has benefited a great deal from omics-based technologies. High-throughput toxicology has defined adverse outcome pathways (AOPs), prioritized chemicals of concern, and identified novel actions of environmental chemicals. While many of these approaches are conducted under rigorous laboratory conditions, a significant challenge has been the interpretation of omics data in "real-world" exposure scenarios. Clarity in the interpretation of these data limits their use in environmental monitoring programs. In recent years, one overarching objective of many has been to address fundamental questions concerning experimental design and the robustness of data collected under the broad umbrella of environmental genomics. These questions include: (1) the likelihood that molecular profiles return to a predefined baseline level following remediation efforts, (2) how reference site selection in an urban environment influences interpretation of omics data and (3) what is the most appropriate species to monitor in the environment from an omics point of view. In addition, inter-genomics studies have been conducted to assess transcriptome reproducibility in toxicology studies. One lesson learned from inter-genomics studies is that there are core molecular networks that can be identified by multiple laboratories using the same platform. This supports the idea that "omics-networks" defined a priori may be a viable approach moving forward for evaluating environmental impacts over time. Both spatial and temporal variability in ecosystem structure is expected to influence molecular responses to environmental stressors, and it is important to recognize how these variables, as well as individual factor (i.e. sex, age, maturation), may confound interpretation of network responses to chemicals. This mini-review synthesizes the progress made towards adopting these tools into environmental monitoring and identifies future challenges to be addressed, as we move into the next era of high throughput sequencing. A conceptual framework for validating and incorporating molecular networks into environmental monitoring programs is proposed. As AOPs become more defined and their potential in environmental monitoring assessments becomes more recognized, the AOP framework may prove to be the conduit between omics and penultimate ecological responses for environmental risk assessments. Copyright © 2018 Elsevier B.V. All rights reserved.

Gas solubility in dilute solutions: A novel molecular thermodynamic perspective

NASA Astrophysics Data System (ADS)

Chialvo, Ariel A.

2018-05-01

We present an explicit molecular-based interpretation of the thermodynamic phase equilibrium underlying gas solubility in liquids, through rigorous links between the microstructure of the dilute systems and the relevant macroscopic quantities that characterize their solution thermodynamics. We apply the formal analysis to unravel and highlight the molecular-level nature of the approximations behind the widely used Krichevsky-Kasarnovsky [J. Am. Chem. Soc. 57, 2168 (1935)] and Krichevsky-Ilinskaya [Acta Physicochim. 20, 327 (1945)] equations for the modeling of gas solubility. Then, we implement a general molecular-based approach to gas solubility and illustrate it by studying Lennard-Jones binary systems whose microstructure and thermodynamic properties were consistently generated via integral equation calculations. Furthermore, guided by the molecular-based analysis, we propose a novel macroscopic modeling approach to gas solubility, emphasize some usually overlook modeling subtleties, and identify novel interdependences among relevant solubility quantities that can be used as either handy modeling constraints or tools for consistency tests.

Gas solubility in dilute solutions: A novel molecular thermodynamic perspective.

PubMed

Chialvo, Ariel A

2018-05-07

We present an explicit molecular-based interpretation of the thermodynamic phase equilibrium underlying gas solubility in liquids, through rigorous links between the microstructure of the dilute systems and the relevant macroscopic quantities that characterize their solution thermodynamics. We apply the formal analysis to unravel and highlight the molecular-level nature of the approximations behind the widely used Krichevsky-Kasarnovsky [J. Am. Chem. Soc. 57, 2168 (1935)] and Krichevsky-Ilinskaya [Acta Physicochim. 20, 327 (1945)] equations for the modeling of gas solubility. Then, we implement a general molecular-based approach to gas solubility and illustrate it by studying Lennard-Jones binary systems whose microstructure and thermodynamic properties were consistently generated via integral equation calculations. Furthermore, guided by the molecular-based analysis, we propose a novel macroscopic modeling approach to gas solubility, emphasize some usually overlook modeling subtleties, and identify novel interdependences among relevant solubility quantities that can be used as either handy modeling constraints or tools for consistency tests.

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.

Structural and vibrational studies on 1-(5-methyl-[1,3,4] thiadiazol-2-yl)-pyrolidin-2-ol

NASA Astrophysics Data System (ADS)

Ramesh Babu, N.; Saleem, H.; Subashchandrabose, S.; Padusha, M. Syed Ali; Bharanidharan, S.

2016-01-01

FT-Raman and FT-IR spectra were recorded for1-(5-methyl-[1,3,4]thiadiazol-2-yl)-pyrolidin-2-ol (MTPN) sample in solid state. The equilibrium geometries, harmonic vibrational frequencies, IR and the Raman scattering intensities were computed using DFT/6-311++G (d,p) level. Results obtained at this level of theory were used for a detailed interpretation of the IR and Raman spectra, based on the TED of the normal modes. Molecular parameters such as bond lengths, bond angles and dihedral angles were calculated. The intra-molecular charge transfer was calculated by means of NBO. Hyperconjugative interaction energy was more during the π-π∗ transition. Energy gap of the molecule has been found using HOMO and LUMO calculation, hence the less band gap, which seems to be more stable.

The shortest path is not the one you know: application of biological network resources in precision oncology research.

PubMed

Kuperstein, Inna; Grieco, Luca; Cohen, David P A; Thieffry, Denis; Zinovyev, Andrei; Barillot, Emmanuel

2015-03-01

Several decades of molecular biology research have delivered a wealth of detailed descriptions of molecular interactions in normal and tumour cells. This knowledge has been functionally organised and assembled into dedicated biological pathway resources that serve as an invaluable tool, not only for structuring the information about molecular interactions but also for making it available for biological, clinical and computational studies. With the advent of high-throughput molecular profiling of tumours, close to complete molecular catalogues of mutations, gene expression and epigenetic modifications are available and require adequate interpretation. Taking into account the information about biological signalling machinery in cells may help to better interpret molecular profiles of tumours. Making sense out of these descriptions requires biological pathway resources for functional interpretation of the data. In this review, we describe the available biological pathway resources, their characteristics in terms of construction mode, focus, aims and paradigms of biological knowledge representation. We present a new resource that is focused on cancer-related signalling, the Atlas of Cancer Signalling Networks. We briefly discuss current approaches for data integration, visualisation and analysis, using biological networks, such as pathway scoring, guilt-by-association and network propagation. Finally, we illustrate with several examples the added value of data interpretation in the context of biological networks and demonstrate that it may help in analysis of high-throughput data like mutation, gene expression or small interfering RNA screening and can guide in patients stratification. Finally, we discuss perspectives for improving precision medicine using biological network resources and tools. Taking into account the information about biological signalling machinery in cells may help to better interpret molecular patterns of tumours and enable to put precision oncology into general clinical practice. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Synthesis, X-ray crystallography characterization, vibrational spectroscopic, molecular electrostatic potential maps, thermodynamic properties studies of N,N'-di(p-thiazole)formamidine.

PubMed

Rofouei, M K; Fereyduni, E; Sohrabi, N; Shamsipur, M; Attar Gharamaleki, J; Sundaraganesan, N

2011-01-01

In this work, we will report a combined experimental and theoretical study on molecular and vibrational structure of N,N'-di(p-thiazole)formamidine (DpTF). DpTF has been synthesized and characterized by elemental analysis, FT-IR, FT-Raman, 1H NMR, 13C NMR spectroscopy and X-ray single crystal diffraction. The FT-IR and FT-Raman spectra of DpTF were recorded in the solid phase. The optimized geometry was calculated by HF and B3LYP methods using 6-31G(d) basis set. The FT-IR and FT-Raman spectra of DpTF was calculated at the HF/B3LYP/6-31G(d) level and were interpreted in terms of potential energy distribution (PED) analysis. The scaled theoretical wavenumber showed very good agreement with the experimental values. A detailed interpretation of the infrared and Raman spectra of DpTF was reported. On the basis of vibrational analyses, the thermodynamic properties of the title compound at different temperatures have been calculated, revealing the correlations between Cp,m°, Sm°, Hm° and temperatures. Furthermore, molecular electrostatic potential maps (MESP) and total dipole moment properties of the compound have been calculated. Copyright © 2010 Elsevier B.V. All rights reserved.

THz Spectroscopy and Spectroscopic Database for Astrophysics

NASA Technical Reports Server (NTRS)

Pearson, John C.; Drouin, Brian J.

2006-01-01

Molecule specific astronomical observations rely on precisely determined laboratory molecular data for interpretation. The Herschel Heterodyne Instrument for Far Infrared, a suite of SOFIA instruments, and ALMA are each well placed to expose the limitations of available molecular physics data and spectral line catalogs. Herschel and SOFIA will observe in high spectral resolution over the entire far infrared range. Accurate data to previously unimagined frequencies including infrared ro-vibrational and ro-torsional bands will be required for interpretation of the observations. Planned ALMA observations with a very small beam will reveal weaker emission features requiring accurate knowledge of higher quantum numbers and additional vibrational states. Historically, laboratory spectroscopy has been at the front of submillimeter technology development, but now astronomical receivers have an enormous capability advantage. Additionally, rotational spectroscopy is a relatively mature field attracting little interest from students and funding agencies. Molecular database maintenance is tedious and difficult to justify as research. This severely limits funding opportunities even though data bases require the same level of expertise as research. We report the application of some relatively new receiver technology into a simple solid state THz spectrometer that has the performance required to collect the laboratory data required by astronomical observations. Further detail on the lack of preparation for upcoming missions by the JPL spectral line catalog is given.

THz Spectroscopy and Spectroscopic Database for Astrophysics

NASA Technical Reports Server (NTRS)

Pearson, John C.; Drouin, Brian J.

2006-01-01

Molecule specific astronomical observations rely on precisely determined laboratory molecular data for interpretation. The Herschel Heterodyne Instrument for Far Infrared, a suite of SOFIA instruments, and ALMA are each well placed to expose the limitations of available molecular physics data and spectral line catalogs. Herschel and SOFIA will observe in high spectral resolution over the entire far infrared range. Accurate data to previously unimagined frequencies including infrared ro-vibrational and ro-torsional bands will be required for interpretation of the observations. Planned ALMA observations with a very small beam will reveal weaker emission features requiring accurate knowledge of higher quantum numbers and additional vibrational states. Historically, laboratory spectroscopy has been at the front of submillimeter technology development, but now astronomical receivers have an enormous capability advantage. Additionally, rotational spectroscopy is a relatively mature field attracting little interest from students and funding agencies. Molecular data base maintenance is tedious and difficult to justify as research. This severely limits funding opportunities even though data bases require the same level of expertise as research. We report the application of some relatively new receiver technology into a simple solid state THz spectrometer that has the performance required to collect the laboratory data required by astronomical observations. Further detail on the lack of preparation for upcoming missions by the JPL spectral line catalog is given.

Molecular heterogeneity at the network level: high-dimensional testing, clustering and a TCGA case study.

PubMed

Städler, Nicolas; Dondelinger, Frank; Hill, Steven M; Akbani, Rehan; Lu, Yiling; Mills, Gordon B; Mukherjee, Sach

2017-09-15

Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging. Furthermore, since network differences could provide important and biologically interpretable information to identify molecular subgroups, there is a need to consider the unsupervised task of learning subgroups and networks that define them. This is a nontrivial clustering problem, with neither subgroups nor subgroup-specific networks known at the outset. We leverage recent ideas from high-dimensional statistics for testing and clustering in the network biology setting. The methods we describe can be applied directly to most continuous molecular measurements and networks do not need to be specified beforehand. We illustrate the ideas and methods in a case study using protein data from The Cancer Genome Atlas (TCGA). This provides evidence that patterns of interplay between signalling proteins differ significantly between cancer types. Furthermore, we show how the proposed approaches can be used to learn subtypes and the molecular networks that define them. As the Bioconductor package nethet. staedler.n@gmail.com or sach.mukherjee@dzne.de. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Molecular modeling: An open invitation for applied mathematics

NASA Astrophysics Data System (ADS)

Mezey, Paul G.

2013-10-01

Molecular modeling methods provide a very wide range of challenges for innovative mathematical and computational techniques, where often high dimensionality, large sets of data, and complicated interrelations imply a multitude of iterative approximations. The physical and chemical basis of these methodologies involves quantum mechanics with several non-intuitive aspects, where classical interpretation and classical analogies are often misleading or outright wrong. Hence, instead of the everyday, common sense approaches which work so well in engineering, in molecular modeling one often needs to rely on rather abstract mathematical constraints and conditions, again emphasizing the high level of reliance on applied mathematics. Yet, the interdisciplinary aspects of the field of molecular modeling also generates some inertia and perhaps too conservative reliance on tried and tested methodologies, that is at least partially caused by the less than up-to-date involvement in the newest developments in applied mathematics. It is expected that as more applied mathematicians take up the challenge of employing the latest advances of their field in molecular modeling, important breakthroughs may follow. In this presentation some of the current challenges of molecular modeling are discussed.

Interpretation of pH-activity profiles for acid-base catalysis from molecular simulations.

PubMed

Dissanayake, Thakshila; Swails, Jason M; Harris, Michael E; Roitberg, Adrian E; York, Darrin M

2015-02-17

The measurement of reaction rate as a function of pH provides essential information about mechanism. These rates are sensitive to the pK(a) values of amino acids directly involved in catalysis that are often shifted by the enzyme active site environment. Experimentally observed pH-rate profiles are usually interpreted using simple kinetic models that allow estimation of "apparent pK(a)" values of presumed general acid and base catalysts. One of the underlying assumptions in these models is that the protonation states are uncorrelated. In this work, we introduce the use of constant pH molecular dynamics simulations in explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a tool to aid in the interpretation of pH-activity data of enzymes and to test the validity of different kinetic models. We apply the methods to RNase A, a prototype acid-base catalyst, to predict the macroscopic and microscopic pK(a) values, as well as the shape of the pH-rate profile. Results for apo and cCMP-bound RNase A agree well with available experimental data and suggest that deprotonation of the general acid and protonation of the general base are not strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling, however, is predicted for the Lys41 and His119 protonation states in apo RNase A, leading to the requirement for a microscopic kinetic model. This type of analysis may be important for other catalytic systems where the active forms of the implicated general acid and base are oppositely charged and more highly correlated. These results suggest a new way for CpHMD/pH-REMD simulations to bridge the gap with experiments to provide a molecular-level interpretation of pH-activity data in studies of enzyme mechanisms.

Interpretation of pH-activity Profiles for Acid-Base Catalysis from Molecular Simulations

PubMed Central

Dissanayake, Thakshila; Swails, Jason; Harris, Michael E.; Roitberg, Adrian E.; York, Darrin M.

2015-01-01

The measurement of reaction rate as a function of pH provides essential information about mechanism. These rates are sensitive to the pKa values of amino acids directly involved in catalysis that are often shifted by the enzyme active site environment. Experimentally observed pH-rate profiles are usually interpreted using simple kinetic models that allow estimation of “apparent pKa” values of presumed general acid and base catalysts. One of the underlying assumptions in these models is that the protonation states are uncorrelated. In the present work, we introduce the use of constant pH molecular dynamics simulations in explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a tool to aid in the interpretation of pH-activity data of enzymes, and test the validity of different kinetic models. We apply the methods to RNase A, a prototype acid/base catalyst, to predict the macroscopic and microscopic pKa values, as well as the shape of the pH-rate profile. Results for apo and cCMP-bound RNase A agree well with available experimental data, and suggest that deprotonation of the general acid and protonation of the general base are not strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling, however, is predicted for the Lys41 and His119 protonation states in apo RNase A, leading to the requirement for a microscopic kinetic model. This type of analysis may be important for other catalytic systems where the active forms of implicated general acid and base are oppositely charged and more highly correlated. These results suggest a new way for CpHMD/pH-REMD simulations to bridge the gap with experiments to provide a molecular-level interpretation of pH-activity data in studies of enzyme mechanisms. PMID:25615525

Kinetic Roughening and Energetics of Tetragonal Lysozyme Crystal Growth: A Preliminary Atomic Force Microscopy Investigation

NASA Technical Reports Server (NTRS)

Gorti, Sridhar; Forsythe, Elizabeth L.; Pusey, Marc L.

2004-01-01

We examined particulars of crystal growth from measurements obtained at both microscopic and molecular levels. The crystal growth measurements performed at the microscopic level are well characterized by a model that balances the flux of macromolecules towards the crystal surface with the flux of the crystal surface. Numerical evaluation of model with measurements of crystal growth, in time, provided accurate estimates for the average growth velocities. Growth velocities thus obtained were also interpreted using well-established phenomenological theories. Moreover, we find that microscopic measurements of growth velocity measurements obtained as a function of temperature best characterizes changes in crystal growth modes, when present. We also examined the possibility of detecting a change in crystal growth modes at the molecular level using atomic force microscopy, AFM. From preliminary AFM measurements performed at various supersaturations, we find that magnitude of surface height fluctuations, h(x), increases with supersaturation. Further examination of surface height fluctuations using methods established for fluctuation spectroscopy also enabled the discovery of the existence of a characteristic length, c, which may possibly determine the mode of crystal growth. Although the results are preliminary, we establish the non- critical divergence of 5 and the root-mean-square (rms) magnitude of height-height fluctuations as the kinetic roughening transition temperatures are approached. Moreover, we also examine approximate models for interpreting the non-critical behavior of both 6 and rms magnitude of height-height fluctuations, as the solution supersaturation is increased towards the kinetic roughening supersaturation.

Evaluation of a u.s. Public health laboratory service for the molecular detection of drug resistant tuberculosis.

PubMed

Yakrus, Mitchell A; Metchock, Beverly; Starks, Angela M

2015-01-01

Crucial to interrupting the spread of tuberculosis (TB) is prompt implementation of effective treatment regimens. We evaluated satisfaction, comfort with interpretation, and use of molecular results from a public health service provided by the Centers for Disease Control and Prevention (CDC) for the molecular detection of drug resistant Mycobacterium tuberculosis complex (MTBC). An electronic survey instrument was used to collect information anonymously from U.S. Public Health Laboratories (PHL) that submitted at least one isolate of MTBC to CDC from September 2009 through February 2011. Over 97% of those responding expressed satisfaction with the turnaround time for receiving results. Twenty-six PHL (74%) reported molecular results to healthcare providers in less than two business days. When comparing the molecular results from CDC with their own phenotypic drug susceptibility testing, 50% of PHL observed discordance. No respondents found the molecular results difficult to interpret and 82% were comfortably discussing them with TB program officials and healthcare providers. Survey results indicate PHL were satisfied with CDC's ability to rapidly provide interpretable molecular results for isolates of MTBC submitted for determination of drug resistance. To develop educational materials and strategies for service improvement, reasons for discordant results and areas of confusion need to be identified.

Rotational Dynamics of Proteins from Spin Relaxation Times and Molecular Dynamics Simulations.

PubMed

Ollila, O H Samuli; Heikkinen, Harri A; Iwaï, Hideo

2018-06-14

Conformational fluctuations and rotational tumbling of proteins can be experimentally accessed with nuclear spin relaxation experiments. However, interpretation of molecular dynamics from the experimental data is often complicated, especially for molecules with anisotropic shape. Here, we apply classical molecular dynamics simulations to interpret the conformational fluctuations and rotational tumbling of proteins with arbitrarily anisotropic shape. The direct calculation of spin relaxation times from simulation data did not reproduce the experimental data. This was successfully corrected by scaling the overall rotational diffusion coefficients around the protein inertia axes with a constant factor. The achieved good agreement with experiments allowed the interpretation of the internal and overall dynamics of proteins with significantly anisotropic shape. The overall rotational diffusion was found to be Brownian, having only a short subdiffusive region below 0.12 ns. The presented methodology can be applied to interpret rotational dynamics and conformation fluctuations of proteins with arbitrary anisotropic shape. However, a water model with more realistic dynamical properties is probably required for intrinsically disordered proteins.

Integrating Omics Technologies to Study Pulmonary Physiology and Pathology at the Systems Level

PubMed Central

Pathak, Ravi Ramesh; Davé, Vrushank

2014-01-01

Assimilation and integration of “omics” technologies, including genomics, epigenomics, proteomics, and metabolomics has readily altered the landscape of medical research in the last decade. The vast and complex nature of omics data can only be interpreted by linking molecular information at the organismic level, forming the foundation of systems biology. Research in pulmonary biology/medicine has necessitated integration of omics, network, systems and computational biology data to differentially diagnose, interpret, and prognosticate pulmonary diseases, facilitating improvement in therapy and treatment modalities. This review describes how to leverage this emerging technology in understanding pulmonary diseases at the systems level –called a “systomic” approach. Considering the operational wholeness of cellular and organ systems, diseased genome, proteome, and the metabolome needs to be conceptualized at the systems level to understand disease pathogenesis and progression. Currently available omics technology and resources require a certain degree of training and proficiency in addition to dedicated hardware and applications, making them relatively less user friendly for the pulmonary biologist and clinicians. Herein, we discuss the various strategies, computational tools and approaches required to study pulmonary diseases at the systems level for biomedical scientists and clinical researchers. PMID:24802001

Molecular structure activity on pharmaceutical applications of Phenacetin using spectroscopic investigation

NASA Astrophysics Data System (ADS)

Madanagopal, A.; Periandy, S.; Gayathri, P.; Ramalingam, S.; Xavier, S.

2017-01-01

The pharmaceutical compound; Phenacetin was investigated by analyzing FT-IR, FT-Raman and 1H &13C NMR spectra. The hybrid efficient computational calculations performed for computing physical and chemical parameters. The cause of pharmaceutical activity due to the substitutions; carboxylic, methyl and amine groups in appropriate positions on the pedestal compound was deeply investigated. Moreover, 13C NMR and 1H NMR chemical shifts correlated with TMS standard to explain the truth of compositional ratio of base and ligand groups. The bathochromic shift due to chromophores over the energy levels in UV-Visible region was strongly emphasized the Anti-inflammatory chemical properties. The chemical stability was pronounced by the strong kubo gap which showed the occurring of charge transformation within the molecule. The occurrence of the chemical reaction was feasibly interpreted by Gibbs free energy profile. The standard vibrational analysis stressed the active participation of composed ligand groups for the existence of the analgesic as well as antipyretic properties of the Phenacetin compound. The strong dipole interaction energy utilization for the transition among non-vanishing donor and acceptor for composition of the molecular structure was interpreted.

Systematically linking tranSMART, Galaxy and EGA for reusing human translational research data

PubMed Central

Zhang, Chao; Bijlard, Jochem; Staiger, Christine; Scollen, Serena; van Enckevort, David; Hoogstrate, Youri; Senf, Alexander; Hiltemann, Saskia; Repo, Susanna; Pipping, Wibo; Bierkens, Mariska; Payralbe, Stefan; Stringer, Bas; Heringa, Jaap; Stubbs, Andrew; Bonino Da Silva Santos, Luiz Olavo; Belien, Jeroen; Weistra, Ward; Azevedo, Rita; van Bochove, Kees; Meijer, Gerrit; Boiten, Jan-Willem; Rambla, Jordi; Fijneman, Remond; Spalding, J. Dylan; Abeln, Sanne

2017-01-01

The availability of high-throughput molecular profiling techniques has provided more accurate and informative data for regular clinical studies. Nevertheless, complex computational workflows are required to interpret these data. Over the past years, the data volume has been growing explosively, requiring robust human data management to organise and integrate the data efficiently. For this reason, we set up an ELIXIR implementation study, together with the Translational research IT (TraIT) programme, to design a data ecosystem that is able to link raw and interpreted data. In this project, the data from the TraIT Cell Line Use Case (TraIT-CLUC) are used as a test case for this system. Within this ecosystem, we use the European Genome-phenome Archive (EGA) to store raw molecular profiling data; tranSMART to collect interpreted molecular profiling data and clinical data for corresponding samples; and Galaxy to store, run and manage the computational workflows. We can integrate these data by linking their repositories systematically. To showcase our design, we have structured the TraIT-CLUC data, which contain a variety of molecular profiling data types, for storage in both tranSMART and EGA. The metadata provided allows referencing between tranSMART and EGA, fulfilling the cycle of data submission and discovery; we have also designed a data flow from EGA to Galaxy, enabling reanalysis of the raw data in Galaxy. In this way, users can select patient cohorts in tranSMART, trace them back to the raw data and perform (re)analysis in Galaxy. Our conclusion is that the majority of metadata does not necessarily need to be stored (redundantly) in both databases, but that instead FAIR persistent identifiers should be available for well-defined data ontology levels: study, data access committee, physical sample, data sample and raw data file. This approach will pave the way for the stable linkage and reuse of data. PMID:29123641

Systematically linking tranSMART, Galaxy and EGA for reusing human translational research data.

PubMed

Zhang, Chao; Bijlard, Jochem; Staiger, Christine; Scollen, Serena; van Enckevort, David; Hoogstrate, Youri; Senf, Alexander; Hiltemann, Saskia; Repo, Susanna; Pipping, Wibo; Bierkens, Mariska; Payralbe, Stefan; Stringer, Bas; Heringa, Jaap; Stubbs, Andrew; Bonino Da Silva Santos, Luiz Olavo; Belien, Jeroen; Weistra, Ward; Azevedo, Rita; van Bochove, Kees; Meijer, Gerrit; Boiten, Jan-Willem; Rambla, Jordi; Fijneman, Remond; Spalding, J Dylan; Abeln, Sanne

2017-01-01

The availability of high-throughput molecular profiling techniques has provided more accurate and informative data for regular clinical studies. Nevertheless, complex computational workflows are required to interpret these data. Over the past years, the data volume has been growing explosively, requiring robust human data management to organise and integrate the data efficiently. For this reason, we set up an ELIXIR implementation study, together with the Translational research IT (TraIT) programme, to design a data ecosystem that is able to link raw and interpreted data. In this project, the data from the TraIT Cell Line Use Case (TraIT-CLUC) are used as a test case for this system. Within this ecosystem, we use the European Genome-phenome Archive (EGA) to store raw molecular profiling data; tranSMART to collect interpreted molecular profiling data and clinical data for corresponding samples; and Galaxy to store, run and manage the computational workflows. We can integrate these data by linking their repositories systematically. To showcase our design, we have structured the TraIT-CLUC data, which contain a variety of molecular profiling data types, for storage in both tranSMART and EGA. The metadata provided allows referencing between tranSMART and EGA, fulfilling the cycle of data submission and discovery; we have also designed a data flow from EGA to Galaxy, enabling reanalysis of the raw data in Galaxy. In this way, users can select patient cohorts in tranSMART, trace them back to the raw data and perform (re)analysis in Galaxy. Our conclusion is that the majority of metadata does not necessarily need to be stored (redundantly) in both databases, but that instead FAIR persistent identifiers should be available for well-defined data ontology levels: study, data access committee, physical sample, data sample and raw data file. This approach will pave the way for the stable linkage and reuse of data.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moberg, Daniel R.; Straight, Shelby C.; Knight, Christopher

Here, an unambiguous assignment of the vibrational spectra of ice I h remains a matter of debate. This study demonstrates that an accurate representation of many-body interactions between water molecules, combined with an explicit treatment of nuclear quantum effects through many-body molecular dynamics (MB-MD), leads to a unified interpretation of the vibrational spectra of ice I h in terms of the structure and dynamics of the underlying hydrogen-bond network. All features of the infrared and Raman spectra in the OH stretching region can be unambiguously assigned by taking into account both the symmetry and the delocalized nature of the latticemore » vibrations as well as the local electrostatic environment experienced by each water molecule within the crystal. The high level of agreement with experiment raises prospects for predictive MB-MD simulations that, complementing analogous measurements, will provide molecular-level insights into fundamental processes taking place in bulk ice and on ice surfaces under different thermodynamic conditions.« less

Synergistic Effects of Toxic Elements on Heat Shock Proteins

PubMed Central

Mahmood, Khalid; Mahmood, Qaisar; Irshad, Muhammad; Hussain, Jamshaid

2014-01-01

Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as “suit of biomarkers in a set of organisms” requires further investigation. PMID:25136596

Students' understanding of primary and secondary protein structure: drawing secondary protein structure reveals student understanding better than simple recognition of structures.

PubMed

Harle, Marissa; Towns, Marcy H

2013-01-01

The interdisciplinary nature of biochemistry courses requires students to use both chemistry and biology knowledge to understand biochemical concepts. Research that has focused on external representations in biochemistry has uncovered student difficulties in comprehending and interpreting external representations in addition to a fragmented understanding of fundamental biochemistry concepts. This project focuses on students' understanding of primary and secondary protein structure and drawings (representations) of hydrogen-bonding in alpha helices and beta sheets. Analysis demonstrated that students can recognize and identify primary protein structure concepts when given a polypeptide. However, when asked to draw alpha helices and beta sheets and explain the role of hydrogen bonding their drawings students exhibited a fragmented understanding that lacked coherence. Faculty are encouraged to have students draw molecular level representations to make their mental models more explicit, complete, and coherent. This is in contrast to recognition and identification tasks, which do not adequately probe mental models and molecular level understanding. © 2013 by The International Union of Biochemistry and Molecular Biology.

On the physical interpretation of the nuclear molecular orbital energy.

PubMed

Charry, Jorge; Pedraza-González, Laura; Reyes, Andrés

2017-06-07

Recently, several groups have extended and implemented molecular orbital (MO) schemes to simultaneously obtain wave functions for electrons and selected nuclei. Many of these schemes employ an extended Hartree-Fock approach as a first step to find approximate electron-nuclear wave functions and energies. Numerous studies conducted with these extended MO methodologies have explored various effects of quantum nuclei on physical and chemical properties. However, to the best of our knowledge no physical interpretation has been assigned to the nuclear molecular orbital energy (NMOE) resulting after solving extended Hartree-Fock equations. This study confirms that the NMOE is directly related to the molecular electrostatic potential at the position of the nucleus.

Molecular simulations enlighten the binding mode of quercetin to lipoxygenase-3.

PubMed

Fiorucci, Sébastien; Golebiowski, Jérôme; Cabrol-Bass, Daniel; Antonczak, Serge

2008-11-01

Inhibition of lipoxygenases (LOXs) by flavonoid compounds is now well documented, but the description of the associated mechanism remains controversial due to a lack of information at the molecular level. For instance, X-ray determination of quercetin/LOX-3 system has led to a structure where the enzyme was cocrystallized with a degradation product of the substrate, which rendered the interpretation of the reported interactions between this flavonoid compound and the enzyme difficult. Molecular modeling simulations can in principle allow obtaining precious insights that could fill this lack of structural information. Thus, in this study, we have investigated various binding modes of quercetin to LOX-3 enzyme in order to understand the first step of the inhibition process, that is the association of the two entities. Molecular dynamics simulations and free energy calculations suggest that quercetin binds the metal center via its 3-hydroxychromone function. Moreover, enzyme/substrate interactions within the cavity impose steric hindrances to quercetin that may activate a direct dioxygen addition on the substrate. (c) 2008 Wiley-Liss, Inc.

From playfulness and self-centredness via grand expectations to normalisation: a psychoanalytical rereading of the history of molecular genetics.

PubMed

Zwart, H A E

2013-11-01

In this paper, I will reread the history of molecular genetics from a psychoanalytical angle, analysing it as a case history. Building on the developmental theories of Freud and his followers, I will distinguish four stages, namely: (1) oedipal childhood, notably the epoch of model building (1943-1953); (2) the latency period, with a focus on the development of basic skills (1953-1989); (3) adolescence, exemplified by the Human Genome Project, with its fierce conflicts, great expectations and grandiose claims (1989-2003) and (4) adulthood (2003-present) during which revolutionary research areas such as molecular biology and genomics have achieved a certain level of normalcy--have evolved into a normal science. I will indicate how a psychoanalytical assessment conducted in this manner may help us to interpret and address some of the key normative issues that have been raised with regard to molecular genetics over the years, such as 'relevance', 'responsible innovation' and 'promise management'.

Identification of a Divergent Environmental DNA Sequence Clade Using the Phylogeny of Gregarine Parasites (Apicomplexa) from Crustacean Hosts

PubMed Central

Rueckert, Sonja; Simdyanov, Timur G.; Aleoshin, Vladimir V.; Leander, Brian S.

2011-01-01

Background Environmental SSU rDNA surveys have significantly improved our understanding of microeukaryotic diversity. Many of the sequences acquired using this approach are closely related to lineages previously characterized at both morphological and molecular levels, making interpretation of these data relatively straightforward. Some sequences, by contrast, appear to be phylogenetic orphans and are sometimes inferred to represent “novel lineages” of unknown cellular identity. Consequently, interpretation of environmental DNA surveys of cellular diversity rely on an adequately comprehensive database of DNA sequences derived from identified species. Several major taxa of microeukaryotes, however, are still very poorly represented in these databases, and this is especially true for diverse groups of single-celled parasites, such as gregarine apicomplexans. Methodology/Principal Findings This study attempts to address this paucity of DNA sequence data by characterizing four different gregarine species, isolated from the intestines of crustaceans, at both morphological and molecular levels: Thiriotia pugettiae sp. n. from the graceful kelp crab (Pugettia gracilis), Cephaloidophora cf. communis from two different species of barnacles (Balanus glandula and B. balanus), Heliospora cf. longissima from two different species of freshwater amphipods (Eulimnogammarus verrucosus and E. vittatus), and Heliospora caprellae comb. n. from a skeleton shrimp (Caprella alaskana). SSU rDNA sequences were acquired from isolates of these gregarine species and added to a global apicomplexan alignment containing all major groups of gregarines characterized so far. Molecular phylogenetic analyses of these data demonstrated that all of the gregarines collected from crustacean hosts formed a very strongly supported clade with 48 previously unidentified environmental DNA sequences. Conclusions/Significance This expanded molecular phylogenetic context enabled us to establish a major clade of intestinal gregarine parasites and infer the cellular identities of several previously unidentified environmental SSU rDNA sequences, including several sequences that have formerly been discussed broadly in the literature as a suspected “novel” lineage of eukaryotes. PMID:21483868

Composition and formation of heterochromatin in Arabidopsis thaliana.

PubMed

Fransz, P; ten Hoopen, R; Tessadori, F

2006-01-01

The term heterochromatin has been applied to both large-scale, microscopically visible chromocentres and small-scale, silent genes located outside chromocentres. This may cause confusion in the interpretation of epigenetic marks for both features. The model plant Arabidopsis thaliana provides an excellent system to investigate composition and function of chromatin states at different levels of organization. In this review we will discuss recent developments in molecular networks underlying gene silencing and the relationship with visible heterochromatin in Arabidopsis.

Complementary online aerosol mass spectrometry and offline FT-IR spectroscopy measurements: Prospects and challenges for the analysis of anthropogenic aerosol particle emissions

NASA Astrophysics Data System (ADS)

Faber, Peter; Drewnick, Frank; Bierl, Reinhard; Borrmann, Stephan

2017-10-01

The aerosol mass spectrometer (AMS) is well established in investigating highly time-resolved dynamics of submicron aerosol chemical composition including organic aerosol (OA). However, interpretation of mass spectra on molecular level is limited due to strong fragmentation of organic substances and potential reactions inside the AMS ion chamber. Results from complementary filter-based FT-IR absorption measurements were used to explain features in high-resolution AMS mass spectra of different types of OA (e.g. cooking OA, cigarette smoking OA, wood burning OA). Using this approach some AMS fragment ions were validated in this study as appropriate and rather specific markers for a certain class of organic compounds for all particle types under investigation. These markers can therefore be used to get deeper insights in the chemical composition of OA based on AMS mass spectra in upcoming studies. However, the specificity of other fragment ions such as C2H4O2+ (m/z 60.02114) remains ambiguous. In such cases, complementary FT-IR measurements allow the interpretation of highly time-resolved AMS mass spectra at the level of molecular functional groups. Furthermore, this study discusses the challenges in reducing inorganic interferences (e.g. from water and ammonium salts) in FT-IR spectra of atmospheric aerosols to decrease spectral uncertainties for better comparisons and, thus, to get more robust results.

Lanthanide and transition metal complexes of bioactive coumarins: molecular modeling and spectroscopic studies.

PubMed

Georgieva, I; Mihaylov, Tz; Trendafilova, N

2014-06-01

The present paper summarizes theoretical and spectroscopic investigations on a series of active coumarins and their lanthanide and transition metal complexes with application in medicine and pharmacy. Molecular modeling as well as IR, Raman, NMR and electronic spectral simulations at different levels of theory were performed to obtain important molecular descriptors: total energy, formation energy, binding energy, stability, conformations, structural parameters, electron density distribution, molecular electrostatic potential, Fukui functions, atomic charges, and reactive indexes. The computations are performed both in gas phase and in solution with consideration of the solvent effect on the molecular structural and energetic parameters. The investigations have shown that the advanced computational methods are reliable for prediction of the metal-coumarin binding mode, electron density distribution, thermodynamic properties as well as the strength and nature of the metal-coumarin interaction (not experimentally accessible) and correctly interpret the experimental spectroscopic data. Known results from biological tests for cytotoxic, antimicrobial, anti-fungal, spasmolytic and anti-HIV activities on the studied metal complexes are reported and discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Informatics and computational strategies for the study of lipids.

PubMed

Yetukuri, Laxman; Ekroos, Kim; Vidal-Puig, Antonio; Oresic, Matej

2008-02-01

Recent advances in mass spectrometry (MS)-based techniques for lipidomic analysis have empowered us with the tools that afford studies of lipidomes at the systems level. However, these techniques pose a number of challenges for lipidomic raw data processing, lipid informatics, and the interpretation of lipidomic data in the context of lipid function and structure. Integration of lipidomic data with other systemic levels, such as genomic or proteomic, in the context of molecular pathways and biophysical processes provides a basis for the understanding of lipid function at the systems level. The present report, based on the limited literature, is an update on a young but rapidly emerging field of lipid informatics and related pathway reconstruction strategies.

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.

Comparative studies on molecular structure, vibrational spectra and hyperpolarizabilies of NLO chromophore Ethyl 4-Dimethylaminobenzoate

NASA Astrophysics Data System (ADS)

Amalanathan, M.; Jasmine, G. Femina; Roy, S. Dawn Dharma

2017-08-01

The molecular structure, vibrational spectra and polarizabilities of Ethyl 4-Dimethylaminobenzoate (EDAB) was investigated by density functional theory employing Becke's three parameter hybrid exchange functional with Lee-Yang-Parr (B3LYP) co-relational functional involving 6-311++G(d,p) basis set and compared with some other levels. A detailed interpretation of the IR and Raman spectra of EDBA have been reported and analyzed. Complete vibrational assignments of the vibrational modes have been done on the basis of the potential energy distribution (TED) using VEDA software. The molecular electrostatic potential mapped onto total density surface has been obtained. A study on the electronic properties, such as absorption wavelength, and frontier molecular orbitals energy, was performed using DFT approach. The stability of the molecule arising from hyper conjugative interactions and accompanying charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The natural and Mulliken charge also calculated and compared with different level of calculation. The dipole moment, polarizability and first, second order hyperpolarizabilities of the title molecule were calculated and compared with the experimental values. The energy gap between frontier orbitals has been used along with electric moments and first order hyperpolarizability, to understand the non linear optical (NLO) activity of the molecule. The NLO activity of molecule was confirmed by SHG analysis.

Green Web or megabiased clock? Plant fossils from Gondwanan Patagonia speak on evolutionary radiations.

PubMed

Wilf, Peter; Escapa, Ignacio H

2015-07-01

Evolutionary divergence-age estimates derived from molecular 'clocks' are frequently correlated with paleogeographic, paleoclimatic and extinction events. One prominent hypothesis based on molecular data states that the dominant pattern of Southern Hemisphere biogeography is post-Gondwanan clade origins and subsequent dispersal across the oceans in a metaphoric 'Green Web'. We tested this idea against well-dated Patagonian fossils of 19 plant lineages, representing organisms that actually lived on Gondwana. Most of these occurrences are substantially older than their respective, often post-Gondwanan molecular dates. The Green Web interpretation probably results from directional bias in molecular results. Gondwanan history remains fundamental to understanding Southern Hemisphere plant radiations, and we urge significantly greater caution when using molecular dating to interpret the biological impacts of geological events. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Proteomic data analysis of glioma cancer stem-cell lines based on novel nonlinear dimensional data reduction techniques

NASA Astrophysics Data System (ADS)

Lespinats, Sylvain; Pinker-Domenig, Katja; Wengert, Georg; Houben, Ivo; Lobbes, Marc; Stadlbauer, Andreas; Meyer-Bäse, Anke

2016-05-01

Glioma-derived cancer stem cells (GSCs) are tumor-initiating cells and may be refractory to radiation and chemotherapy and thus have important implications for tumor biology and therapeutics. The analysis and interpretation of large proteomic data sets requires the development of new data mining and visualization approaches. Traditional techniques are insufficient to interpret and visualize these resulting experimental data. The emphasis of this paper lies in the application of novel approaches for the visualization, clustering and projection representation to unveil hidden data structures relevant for the accurate interpretation of biological experiments. These qualitative and quantitative methods are applied to the proteomic analysis of data sets derived from the GSCs. The achieved clustering and visualization results provide a more detailed insight into the protein-level fold changes and putative upstream regulators for the GSCs. However the extracted molecular information is insufficient in classifying GSCs and paving the pathway to an improved therapeutics of the heterogeneous glioma.

Communication: Hilbert-space partitioning of the molecular one-electron density matrix with orthogonal projectors

NASA Astrophysics Data System (ADS)

Vanfleteren, Diederik; Van Neck, Dimitri; Bultinck, Patrick; Ayers, Paul W.; Waroquier, Michel

2010-12-01

A double-atom partitioning of the molecular one-electron density matrix is used to describe atoms and bonds. All calculations are performed in Hilbert space. The concept of atomic weight functions (familiar from Hirshfeld analysis of the electron density) is extended to atomic weight matrices. These are constructed to be orthogonal projection operators on atomic subspaces, which has significant advantages in the interpretation of the bond contributions. In close analogy to the iterative Hirshfeld procedure, self-consistency is built in at the level of atomic charges and occupancies. The method is applied to a test set of about 67 molecules, representing various types of chemical binding. A close correlation is observed between the atomic charges and the Hirshfeld-I atomic charges.

Detection of an oxygen atmosphere on Jupiter's moon Europa.

PubMed

Hall, D T; Strobel, D F; Feldman, P D; McGrath, M A; Weaver, H A

1995-02-23

Europa, the second large satellite out from Jupiter, is roughly the size of Earth's Moon, but unlike the Moon, it has water ice on its surface. There have been suggestions that an oxygen atmosphere should accumulate around such a body, through reactions which break up the water molecules and form molecular hydrogen and oxygen. The lighter H2 molecules would escape from Europa relatively easily, leaving behind an atmosphere rich in oxygen. Here we report the detection of atomic oxygen emission from Europa, which we interpret as being produced by the simultaneous dissociation and excitation of atmospheric O2 by electrons from Jupiter's magnetosphere. Europa's molecular oxygen atmosphere is very tenuous, with a surface pressure about 10(-11) that of the Earth's atmosphere at sea level.

A Model for Atomic and Molecular Interstellar Gas: The Meudon PDR Code

NASA Astrophysics Data System (ADS)

Le Petit, Franck; Nehmé, Cyrine; Le Bourlot, Jacques; Roueff, Evelyne

2006-06-01

We present the revised ``Meudon'' model of photon-dominated region (PDR) code, available on the Web under the GNU Public License. General organization of the code is described down to a level that should allow most observers to use it as an interpretation tool with minimal help from our part. Two grids of models, one for low-excitation diffuse clouds and one for dense highly illuminated clouds, are discussed, and some new results on PDR modelization highlighted.

Using Multiple Representations to Resolve Conflict in Student Conceptual Understanding of Chemistry

NASA Astrophysics Data System (ADS)

Daubenmire, Paul L.

Much like a practiced linguist, expert chemists utilize the power and elegance of chemical symbols to understand what is happening at the atomic level and to manipulate atoms and molecules to effect an observable change at the macroscopic level. Unfortunately, beginning chemistry is often taught in a way that emphasizes memorizing the symbolic representations of equations and reactions without much opportunity to meaningfully connect the observable macroscopic phenomena with an understanding of the chemistry taking place at the atomic level. The compartmentalized manner of chemistry instruction in most chemistry classrooms further nullifies the efficacy of the triplet relationship to connect between macroscopic observations, symbolic representations, and atomic scale views. If symbolic representations are presented as the goal of instruction, rather than as the means to gain understanding, then students will be impaired in developing a coherent understanding of chemical principles. This dissertation describes the development and implementation of an interview study to examine how undergraduate students interpreted multiple representations of a chemical equilibrium. To establish a baseline of ideas, students first were coached to verbally generate successive representations. They were then cued to think about the chemistry occurring between atoms and ions at the molecular level. Next, an experiment involving a change in states of matter and color was performed which paralleled the symbolic representations. Through self-explanations and verbalizing of conjectures, students were encouraged to explore, interpret, and refine their understanding of the observations related to the chemical symbols presented to them. Finally, with the goal of fostering a deeper understanding of the process of equilibrium, a dynamic visualization of the molecular level was introduced as a tool for helping students connect these multiple representations. This study revealed that one way in which students develop conceptual understanding and resolve conflicts between different representations of the same phenomena is by verbalizing their ideas as a conjecture (as a verbal explanation to advance towards a hypothesis). Thus, it is proposed that symbolic representations are most effective viewed not as an end goal but as a bridge for connecting macroscopic, visible phenomena with what is occurring at the molecular, invisible level. When the focus on merely memorizing chemical equations and symbols is removed, students can gain a coherent understanding of the meaning available when multiple representations are viewed together.

FT-Raman, FT-IR spectra and total energy distribution of 3-pentyl-2,6-diphenylpiperidin-4-one: DFT method.

PubMed

Subashchandrabose, S; Saleem, H; Erdogdu, Y; Rajarajan, G; Thanikachalam, V

2011-11-01

FT-Raman and FT-IR spectra were recorded for 3-pentyl-2,6-diphenylpiperidin-4-one (PDPO) sample in solid state. The equilibrium geometries, harmonic vibrational frequencies, infrared and the Raman scattering intensities were computed using DFT/6-31G(d,p) level. Results obtained at this level of theory were used for a detailed interpretation of the infrared and Raman spectra, based on the total energy distribution (TED) of the normal modes. Molecular parameters such as bond lengths, bond angles and dihedral angles were calculated and compared with X-ray diffraction data. This comparison was good agreement. The intra-molecular charge transfer was calculated by means of natural bond orbital analysis (NBO). Hyperconjugative interaction energy was more during the π-π* transition. Energy gap of the molecule was found using HOMO and LUMO calculation, hence the less band gap, which seems to be more stable. Atomic charges of the carbon, nitrogen and oxygen were calculated using same level of calculation. Copyright © 2011 Elsevier B.V. All rights reserved.

Physical conditions in molecular clouds

NASA Technical Reports Server (NTRS)

Evans, Neal J., II

1989-01-01

Recent developments have complicated the picture of the physical conditions in molecular clouds. The discoveries of widespread emission from high-J lines of CD and 12-micron IRAS emission have revealed the presence of considerably hotter gas and dust near the surfaces of molecular clouds. These components can complicate interpretation of the bulk of the cloud gas. Commonly assumed relations between column density or mean density and cloud size are called into question by conflicting results and by consideration of selection effects. Analysis of density and density structure through molecular excitation has shown that very high densities exist in star formation regions, but unresolved structure and possible chemical effects complicate the interpretation. High resolution far-IR and submillimeter observations offer a complementary approach and are beginning to test theoretical predictions of density gradients in clouds.

Quasiparticle Level Alignment for Photocatalytic Interfaces.

PubMed

Migani, Annapaoala; Mowbray, Duncan J; Zhao, Jin; Petek, Hrvoje; Rubio, Angel

2014-05-13

Electronic level alignment at the interface between an adsorbed molecular layer and a semiconducting substrate determines the activity and efficiency of many photocatalytic materials. Standard density functional theory (DFT)-based methods have proven unable to provide a quantitative description of this level alignment. This requires a proper treatment of the anisotropic screening, necessitating the use of quasiparticle (QP) techniques. However, the computational complexity of QP algorithms has meant a quantitative description of interfacial levels has remained elusive. We provide a systematic study of a prototypical interface, bare and methanol-covered rutile TiO2(110) surfaces, to determine the type of many-body theory required to obtain an accurate description of the level alignment. This is accomplished via a direct comparison with metastable impact electron spectroscopy (MIES), ultraviolet photoelectron spectroscopy (UPS), and two-photon photoemission (2PP) spectroscopy. We consider GGA DFT, hybrid DFT, and G0W0, scQPGW1, scQPGW0, and scQPGW QP calculations. Our results demonstrate that G0W0, or our recently introduced scQPGW1 approach, are required to obtain the correct alignment of both the highest occupied and lowest unoccupied interfacial molecular levels (HOMO/LUMO). These calculations set a new standard in the interpretation of electronic structure probe experiments of complex organic molecule/semiconductor interfaces.

Molecular gels in the gas phase? Gelator-gelator and gelator-solvent interactions probed by vibrational spectroscopy.

PubMed

Lozada-Garcia, Rolando; Mu, Dan; Plazanet, Marie; Çarçabal, Pierre

2016-08-10

Benzylidene glucose (BzGlc) is a member of the benzylidene glycoside family. These molecules have the ability to form molecular physical gels. These materials are formed when gelator molecules create a non-covalently bound frame where solvent molecules are trapped. Since the gel formation process and its properties are determined by the subtle balance between non-covalent forces, it is difficult to anticipate them. Quantitative and qualitative understanding of the gelator-gelator and gelator-solvent interactions is needed to better control these materials for important potential applications. We have used gas phase vibrational spectroscopy and theoretical chemistry to study the conformational choices of BzGlc, its dimer and the complexes it forms with water or toluene. To interpret the vibrational spectra we have used the dispersion corrected functional B97D which we have calibrated for the calculation of OH stretching frequencies. Even at the most basic molecular level, it is possible to interrogate a large range of non-covalent interactions ranging from OH → OH hydrogen bonding, to OH → π, and CH → π, all being at the center of gel properties at the macroscopic level.

Conductance manipulation at the molecular level

NASA Astrophysics Data System (ADS)

Paulsson, Magnus; Stafström, Sven

1999-05-01

Using a tight-binding model we have studied the electronic transmission through a C60 molecule sandwiched between a metal surface and a metal (scanning tunnelling microscope) tip. By simulating compression of C60 we have interpreted an experimental study of the variation of the conductance through a C60 molecule with an applied external pressure. We found that the observed increase in conductance cannot be explained in terms of the changes in the electronic structure of the C60 molecule alone. Effects related to the metal/molecule contact, i.e. the strength of the metal/C60 interaction and the shape of the molecular orbitals in the tip, are in fact more important for the conductance. In view of this we discuss the importance of interference effects in the tip/molecule coupling.

Molecular genetics external quality assessment pilot scheme for KRAS analysis in metastatic colorectal cancer.

PubMed

Deans, Zandra C; Tull, Justyna; Beighton, Gemma; Abbs, Stephen; Robinson, David O; Butler, Rachel

2011-11-01

Laboratories are increasingly required to perform molecular tests for the detection of mutations in the KRAS gene in metastatic colorectal cancers to allow better clinical management and more effective treatment for these patients. KRAS mutation status predicts a patient's likely response to the monoclonal antibody cetuximab. To provide a high standard of service, these laboratories require external quality assessment (EQA) to monitor the level of laboratory output and measure the performance of the laboratory against other service providers. National External Quality Assurance Services for Molecular Genetics provided a pilot EQA scheme for KRAS molecular analysis in metastatic colorectal cancers during 2009. Very few genotyping errors were reported by participating laboratories; however, the reporting nomenclature of the genotyping results varied considerably between laboratories. The pilot EQA scheme highlighted the need for continuing EQA in this field which will assess the laboratories' ability not only to obtain accurate, reliable results but also to interpret them safely and correctly ensuring that the referring clinician has the correct information to make the best clinical therapeutic decision for their patient.

Intentions and actions in molecular self-assembly: perspectives on students' language use

NASA Astrophysics Data System (ADS)

Höst, Gunnar E.; Anward, Jan

2017-04-01

Learning to talk science is an important aspect of learning to do science. Given that scientists' language frequently includes intentions and purposes in explanations of unobservable objects and events, teachers must interpret whether learners' use of such language reflects a scientific understanding or inaccurate anthropomorphism and teleology. In the present study, a framework consisting of three 'stances' (Dennett, 1987) - intentional, design and physical - is presented as a powerful tool for analysing students' language use. The aim was to investigate how the framework can be differentiated and used analytically for interpreting students' talk about a molecular process. Semi-structured group discussions and individual interviews about the molecular self-assembly process were conducted with engineering biology/chemistry (n = 15) and biology/chemistry teacher students (n = 6). Qualitative content analysis of transcripts showed that all three stances were employed by students. The analysis also identified subcategories for each stance, and revealed that intentional language with respect to molecular movement and assumptions about design requirements may be potentially problematic areas. Students' exclusion of physical stance explanations may indicate literal anthropomorphic interpretations. Implications for practice include providing teachers with a tool for scaffolding their use of metaphorical language and for supporting students' metacognitive development as scientific language users.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loomis, Ryan A.; McGuire, Brett A.; Remijan, Anthony J.

Recently, Lattelais et al. have interpreted aggregated observations of molecular isomers to suggest that there exists a ''minimum energy principle'', such that molecular formation will favor more stable molecular isomers for thermodynamic reasons. To test the predictive power of this principle, we have fully characterized the spectra of the three isomers of C{sub 3}H{sub 2}O toward the well-known molecular region Sgr B2(N). Evidence for the detection of the isomers cyclopropenone (c-C{sub 3}H{sub 2}O) and propynal (HCCCHO) is presented, along with evidence for the non-detection of the lowest zero-point energy isomer, propadienone (CH{sub 2}CCO). We interpret these observations as evidence that chemicalmore » formation pathways, which may be under kinetic control, have a more pronounced effect on final isomer abundances than thermodynamic effects such as the minimum energy principle.« less

Variations in the Composition of Gelling Agents Affect Morphophysiological and Molecular Responses to Deficiencies of Phosphate and Other Nutrients1[C][W][OA

PubMed Central

Jain, Ajay; Poling, Michael D.; Smith, Aaron P.; Nagarajan, Vinay K.; Lahner, Brett; Meagher, Richard B.; Raghothama, Kashchandra G.

2009-01-01

Low inorganic phosphate (Pi) availability triggers an array of spatiotemporal adaptive responses in Arabidopsis (Arabidopsis thaliana). There are several reports on the effects of Pi deprivation on the root system that have been attributed to different growth conditions and/or inherent genetic variability. Here we show that the gelling agents, largely treated as inert components, significantly affect morphophysiological and molecular responses of the seedlings to deficiencies of Pi and other nutrients. Inductively coupled plasma-mass spectroscopy analysis revealed variable levels of elemental contaminants not only in different types of agar but also in different batches of the same agar. Fluctuating levels of phosphorus (P) in different agar types affected the growth of the seedlings under Pi-deprivation condition. Since P interacts with other elements such as iron, potassium, and sulfur, contaminating effects of these elements in different agars were also evident in the Pi-deficiency-induced morphological and molecular responses. P by itself acted as a contaminant when studying the responses of Arabidopsis to micronutrient (iron and zinc) deficiencies. Together, these results highlighted the likelihood of erroneous interpretations that could be easily drawn from nutrition studies when different agars have been used. As an alternative, we demonstrate the efficacy of a sterile and contamination-free hydroponic system for dissecting morphophysiological and molecular responses of Arabidopsis to different nutrient deficiencies. PMID:19386810

Quality Assurance Program for Molecular Medicine Laboratories

PubMed Central

Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B

2013-01-01

Background: Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. Methods: We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Results: Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Conclusion: Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level. PMID:23865028

Quality assurance program for molecular medicine laboratories.

PubMed

Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B

2013-01-01

Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level.

Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity

NASA Astrophysics Data System (ADS)

Simon, Joseph R.; Carroll, Nick J.; Rubinstein, Michael; Chilkoti, Ashutosh; López, Gabriel P.

2017-06-01

Dynamic protein-rich intracellular structures that contain phase-separated intrinsically disordered proteins (IDPs) composed of sequences of low complexity (SLC) have been shown to serve a variety of important cellular functions, which include signalling, compartmentalization and stabilization. However, our understanding of these structures and our ability to synthesize models of them have been limited. We present design rules for IDPs possessing SLCs that phase separate into diverse assemblies within droplet microenvironments. Using theoretical analyses, we interpret the phase behaviour of archetypal IDP sequences and demonstrate the rational design of a vast library of multicomponent protein-rich structures that ranges from uniform nano-, meso- and microscale puncta (distinct protein droplets) to multilayered orthogonally phase-separated granular structures. The ability to predict and program IDP-rich assemblies in this fashion offers new insights into (1) genetic-to-molecular-to-macroscale relationships that encode hierarchical IDP assemblies, (2) design rules of such assemblies in cell biology and (3) molecular-level engineering of self-assembled recombinant IDP-rich materials.

Molecular Occupancy of Nanodot Arrays.

PubMed

Cai, Haogang; Wolfenson, Haguy; Depoil, David; Dustin, Michael L; Sheetz, Michael P; Wind, Shalom J

2016-04-26

Single-molecule nanodot arrays, in which a biomolecule of choice (protein, nucleic acid, etc.) is bound to a metallic nanoparticle on a solid substrate, are becoming an increasingly important tool in the study of biomolecular and cellular interactions. We have developed an on-chip measurement protocol to monitor and control the molecular occupancy of nanodots. Arrays of widely spaced nanodots and nanodot clusters were fabricated on glass surfaces by nanolithography and functionalized with fluorescently labeled proteins. The molecular occupancy was determined by monitoring individual fluorophore bleaching events, while accounting for fluorescence quenching effects. We found that the occupancy can be interpreted as a packing problem, and depends on nanodot size and binding ligand concentration, where the latter is easily adjusted to compensate the flexibility of dimension control in nanofabrication. The results are scalable with nanodot cluster size, extending to large area close packed arrays. As an example, the nanoarray platform was used to probe the geometric requirement of T-cell activation at the single-molecule level.

Different molecular organization of two carotenoids, lutein and zeaxanthin, in human colon epithelial cells and colon adenocarcinoma cells

NASA Astrophysics Data System (ADS)

Grudzinski, Wojciech; Piet, Mateusz; Luchowski, Rafal; Reszczynska, Emilia; Welc, Renata; Paduch, Roman; Gruszecki, Wieslaw I.

2018-01-01

Two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of exogenous carotenoids, either zeaxanthin or lutein. Both carotenoids demonstrated cytotoxicity with respect to cancer cells but not to normal cells. Cells from both the cell lines were analyzed with application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. Both imaging techniques show effective incorporation of carotenoid molecules into growing cells. Comparison of the Raman scattering and fluorescence lifetime characteristics reveals different molecular organization of carotenoids in the carcinoma and normal cells. The main difference consists in a carotenoid aggregation level which is substantially lower in the carcinoma cells as compared to the normal cells. Different molecular organization of carotenoids was interpreted in terms of a different metabolism of normal and carcinoma cells and has been concluded to provide a possibility of cancer diagnosis based on spectroscopic analyses.

Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar.

PubMed

Harrison, Steven M; Dolinsky, Jill S; Knight Johnson, Amy E; Pesaran, Tina; Azzariti, Danielle R; Bale, Sherri; Chao, Elizabeth C; Das, Soma; Vincent, Lisa; Rehm, Heidi L

2017-10-01

Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolve interpretation differences by analyzing a subset of variants. ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines, and then compared interpretations. At least two of the participating laboratories interpreted 6,169 variants in ClinVar, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing; 12.8% (31) of reassessed variants remained discordant owing to differences in the application of the ACMG-AMP guidelines. Participating laboratories increased their overall concordance from 88.3 to 91.7%, indicating that sharing variant interpretations in ClinVar-thereby allowing identification of differences and motivation to resolve those differences-is critical to moving toward more consistent variant interpretations.Genet Med advance online publication 09 March 2017.

Nondynamical correlation energy in model molecular systems

NASA Astrophysics Data System (ADS)

Chojnacki, Henryk

The hypersurfaces for the deprotonation processes have been studied at the nonempirical level for H3O+, NH+4, PH+4, and H3S+ cations within their correlation consistent basis set. The potential energy curves were calculated and nondynamical correlation energies analyzed. We have found that the restricted Hartree-Fock wavefunction leads to the improper dissociation limit and, in the three latest cases requires multireference description. We conclude that these systems may be treated as a good models for interpretation of the proton transfer mechanism as well as for testing one-determinantal or multireference cases.

Analyzing and interpreting genome data at the network level with ConsensusPathDB.

PubMed

Herwig, Ralf; Hardt, Christopher; Lienhard, Matthias; Kamburov, Atanas

2016-10-01

ConsensusPathDB consists of a comprehensive collection of human (as well as mouse and yeast) molecular interaction data integrated from 32 different public repositories and a web interface featuring a set of computational methods and visualization tools to explore these data. This protocol describes the use of ConsensusPathDB (http://consensuspathdb.org) with respect to the functional and network-based characterization of biomolecules (genes, proteins and metabolites) that are submitted to the system either as a priority list or together with associated experimental data such as RNA-seq. The tool reports interaction network modules, biochemical pathways and functional information that are significantly enriched by the user's input, applying computational methods for statistical over-representation, enrichment and graph analysis. The results of this protocol can be observed within a few minutes, even with genome-wide data. The resulting network associations can be used to interpret high-throughput data mechanistically, to characterize and prioritize biomarkers, to integrate different omics levels, to design follow-up functional assay experiments and to generate topology for kinetic models at different scales.

Molecular profiling of cancer--the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic.

PubMed

Stricker, Thomas; Catenacci, Daniel V T; Seiwert, Tanguy Y

2011-04-01

Cancers arise as a result of an accumulation of genetic aberrations that are either acquired or inborn. Virtually every cancer has its unique set of molecular changes. Technologies have been developed to study cancers and derive molecular characteristics that increasingly have implications for clinical care. Indeed, the identification of key genetic aberrations (molecular drivers) may ultimately translate into dramatic benefit for patients through the development of highly targeted therapies. With the increasing availability of newer, more powerful, and cheaper technologies such as multiplex mutational screening, next generation sequencing, array-based approaches that can determine gene copy numbers, methylation, expression, and others, as well as more sophisticated interpretation of high-throughput molecular information using bioinformatics tools like signatures and predictive algorithms, cancers will routinely be characterized in the near future. This review examines the background information and technologies that clinicians and physician-scientists will need to interpret in order to develop better, personalized treatment strategies. Copyright © 2011 Elsevier Inc. All rights reserved.

Two-dimensional infrared spectroscopy of vibrational polaritons.

PubMed

Xiang, Bo; Ribeiro, Raphael F; Dunkelberger, Adam D; Wang, Jiaxi; Li, Yingmin; Simpkins, Blake S; Owrutsky, Jeffrey C; Yuen-Zhou, Joel; Xiong, Wei

2018-05-08

We report experimental 2D infrared (2D IR) spectra of coherent light-matter excitations--molecular vibrational polaritons. The application of advanced 2D IR spectroscopy to vibrational polaritons challenges and advances our understanding in both fields. First, the 2D IR spectra of polaritons differ drastically from free uncoupled excitations and a new interpretation is needed. Second, 2D IR uniquely resolves excitation of hybrid light-matter polaritons and unexpected dark states in a state-selective manner, revealing otherwise hidden interactions between them. Moreover, 2D IR signals highlight the impact of molecular anharmonicities which are applicable to virtually all molecular systems. A quantum-mechanical model is developed which incorporates both nuclear and electrical anharmonicities and provides the basis for interpreting this class of 2D IR spectra. This work lays the foundation for investigating phenomena of nonlinear photonics and chemistry of molecular vibrational polaritons which cannot be probed with traditional linear spectroscopy.

The Evolution of Darwinism.

ERIC Educational Resources Information Center

Stebbins, G. Ledyard; Ayala, Francisco J.

1985-01-01

Recent developments in molecular biology and new interpretations of the fossil record are gradually altering and adding to Charles Darwin's theory, which has been the standard view of the process of evolution for 40 years. Several of these developments and interpretations are identified and discussed. (JN)

Tetraphenylporphyrin electronic properties: a combined theoretical and experimental study of thin films deposited by SuMBD.

PubMed

Nardi, Marco; Verucchi, Roberto; Corradi, Claudio; Pola, Marco; Casarin, Maurizio; Vittadini, Andrea; Iannotta, Salvatore

2010-01-28

Porphyrins and their metal complexes are particularly well suitable for applications in photoelectronics, sensing, energy production, because of their chemical, electronic and optical properties. The understanding of the electronic properties of the pristine molecule is of great relevance for the study and application of the wide class of these compounds. This is notably important for the recently achieved in-vacuo synthesis of organo-metallic thin films directly from the pure free base organic-inorganic precursors in the vapor phase, and its interpretation by means of surface electron spectroscopies. We report on a combined experimental and theoretical study of the physical/chemical properties of tetraphenylporphyrin, H(2)TPP, deposited on the SiO(2)/Si(100) native oxide surface by supersonic molecular beam deposition (SuMBD). Valence states and 1s core level emissions of carbon and nitrogen have been investigated with surface photoelectron spectroscopies by using synchrotron radiation light. The interpretation of the spectra has been guided by density functional numerical experiments on the gas-phase molecule. Non-relativistic calculations were carried out for the valence states, whereas a two component relativistic approach in the zeroth-order regular approximation was used to investigate the core levels. The good agreement between theoretical and experimental analysis results in a comprehensive overview of the chemical properties of the H(2)TPP molecule, highly improving reliability in the interpretation of experimental photoemission spectra.

The aims of systems biology: between molecules and organisms.

PubMed

Noble, D

2011-05-01

The systems approach to biology has a long history. Its recent rapid resurgence at the turn of the century reflects the problems encountered in interpreting the sequencing of the genome and the failure of that immense achievement to provide rapid and direct solutions to major multi-factorial diseases. This paper argues that systems biology is necessarily multilevel and that there is no privileged level of causality in biological systems. It is an approach rather than a separate discipline. Functionality arises from biological networks that interact with the genome, the environment and the phenotype. This view of biology is very different from the gene-centred views of neo-Darwinism and molecular biology. In neuroscience, the systems approach leads naturally to 2 important conclusions: first, that the idea of 'programs' in the brain is confusing, and second, that the self is better interpreted as a process than as an object. © Georg Thieme Verlag KG Stuttgart · New York.

Molecular composition and ultrastructure of Jurassic paravian feathers

PubMed Central

Lindgren, Johan; Sjövall, Peter; Carney, Ryan M.; Cincotta, Aude; Uvdal, Per; Hutcheson, Steven W.; Gustafsson, Ola; Lefèvre, Ulysse; Escuillié, François; Heimdal, Jimmy; Engdahl, Anders; Gren, Johan A.; Kear, Benjamin P.; Wakamatsu, Kazumasa; Yans, Johan; Godefroit, Pascal

2015-01-01

Feathers are amongst the most complex epidermal structures known, and they have a well-documented evolutionary trajectory across non-avian dinosaurs and basal birds. Moreover, melanosome-like microbodies preserved in association with fossil plumage have been used to reconstruct original colour, behaviour and physiology. However, these putative ancient melanosomes might alternatively represent microorganismal residues, a conflicting interpretation compounded by a lack of unambiguous chemical data. We therefore used sensitive molecular imaging, supported by multiple independent analytical tests, to demonstrate that the filamentous epidermal appendages in a new specimen of the Jurassic paravian Anchiornis comprise remnant eumelanosomes and fibril-like microstructures, preserved as endogenous eumelanin and authigenic calcium phosphate. These results provide novel insights into the early evolution of feathers at the sub-cellular level, and unequivocally determine that melanosomes can be preserved in fossil feathers. PMID:26311035

Polarizability of acetanilide and RDX in the crystal: effect of molecular geometry

NASA Astrophysics Data System (ADS)

Tsiaousis, D.; Munn, R. W.; Smith, P. J.; Popelier, P. L. A.

2004-10-01

Density-functional theory with the B3LYP functional at the 6-311++G** level is used to calculate the dipole moment and the static polarizability for acetanilide and 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) in their in-crystal structures. For acetanilide the dipole moment is 2{1}/{2}% larger than for the gas-phase structure and for RDX (where there is a gross geometry change) it is 15% larger. The polarizability for the in-crystal structure is smaller than for the gas-phase structure by 3% for both species, whereas the in-crystal effective optical polarizability is larger than the gas-phase static polarizability for both crystals. Hence, effects in addition to the molecular geometry change in the crystal must be considered in order to interpret the effective polarizability completely.

Morphological diagnostics of star formation in molecular clouds

NASA Astrophysics Data System (ADS)

Beaumont, Christopher Norris

Molecular clouds are the birth sites of all star formation in the present-day universe. They represent the initial conditions of star formation, and are the primary medium by which stars transfer energy and momentum back to parsec scales. Yet, the physical evolution of molecular clouds remains poorly understood. This is not due to a lack of observational data, nor is it due to an inability to simulate the conditions inside molecular clouds. Instead, the physics and structure of the interstellar medium are sufficiently complex that interpreting molecular cloud data is very difficult. This dissertation mitigates this problem, by developing more sophisticated ways to interpret morphological information in molecular cloud observations and simulations. In particular, I have focused on leveraging machine learning techniques to identify physically meaningful substructures in the interstellar medium, as well as techniques to inter-compare molecular cloud simulations to observations. These contributions make it easier to understand the interplay between molecular clouds and star formation. Specific contributions include: new insight about the sheet-like geometry of molecular clouds based on observations of stellar bubbles; a new algorithm to disambiguate overlapping yet morphologically distinct cloud structures; a new perspective on the relationship between molecular cloud column density distributions and the sizes of cloud substructures; a quantitative analysis of how projection effects affect measurements of cloud properties; and an automatically generated, statistically-calibrated catalog of bubbles identified from their infrared morphologies.

A semester-long project for teaching basic techniques in molecular biology such as restriction fragment length polymorphism analysis to undergraduate and graduate students.

PubMed

DiBartolomeis, Susan M

2011-01-01

Several reports on science education suggest that students at all levels learn better if they are immersed in a project that is long term, yielding results that require analysis and interpretation. I describe a 12-wk laboratory project suitable for upper-level undergraduates and first-year graduate students, in which the students molecularly locate and map a gene from Drosophila melanogaster called dusky and one of dusky's mutant alleles. The mapping strategy uses restriction fragment length polymorphism analysis; hence, students perform most of the basic techniques of molecular biology (DNA isolation, restriction enzyme digestion and mapping, plasmid vector subcloning, agarose and polyacrylamide gel electrophoresis, DNA labeling, and Southern hybridization) toward the single goal of characterizing dusky and the mutant allele dusky(73). Students work as individuals, pairs, or in groups of up to four students. Some exercises require multitasking and collaboration between groups. Finally, results from everyone in the class are required for the final analysis. Results of pre- and postquizzes and surveys indicate that student knowledge of appropriate topics and skills increased significantly, students felt more confident in the laboratory, and students found the laboratory project interesting and challenging. Former students report that the lab was useful in their careers.

A Semester-Long Project for Teaching Basic Techniques in Molecular Biology Such as Restriction Fragment Length Polymorphism Analysis to Undergraduate and Graduate Students

PubMed Central

DiBartolomeis, Susan M.

2011-01-01

Several reports on science education suggest that students at all levels learn better if they are immersed in a project that is long term, yielding results that require analysis and interpretation. I describe a 12-wk laboratory project suitable for upper-level undergraduates and first-year graduate students, in which the students molecularly locate and map a gene from Drosophila melanogaster called dusky and one of dusky's mutant alleles. The mapping strategy uses restriction fragment length polymorphism analysis; hence, students perform most of the basic techniques of molecular biology (DNA isolation, restriction enzyme digestion and mapping, plasmid vector subcloning, agarose and polyacrylamide gel electrophoresis, DNA labeling, and Southern hybridization) toward the single goal of characterizing dusky and the mutant allele dusky73. Students work as individuals, pairs, or in groups of up to four students. Some exercises require multitasking and collaboration between groups. Finally, results from everyone in the class are required for the final analysis. Results of pre- and postquizzes and surveys indicate that student knowledge of appropriate topics and skills increased significantly, students felt more confident in the laboratory, and students found the laboratory project interesting and challenging. Former students report that the lab was useful in their careers. PMID:21364104

Eliciting Metacognitive Experiences and Reflection in a Year 11 Chemistry Classroom: An Activity Theory Perspective

NASA Astrophysics Data System (ADS)

Thomas, Gregory P.; McRobbie, Campbell J.

2013-06-01

Concerns regarding students' learning and reasoning in chemistry classrooms are well documented. Students' reasoning in chemistry should be characterized by conscious consideration of chemical phenomenon from laboratory work at macroscopic, molecular/sub-micro and symbolic levels. Further, students should develop metacognition in relation to such ways of reasoning about chemistry phenomena. Classroom change eliciting metacognitive experiences and metacognitive reflection is necessary to shift entrenched views of teaching and learning in students. In this study, Activity Theory is used as the framework for interpreting changes to the rules/customs and tools of the activity systems of two different classes of students taught by the same teacher, Frances, who was teaching chemical equilibrium to those classes in consecutive years. An interpretive methodology involving multiple data sources was employed. Frances explicitly changed her pedagogy in the second year to direct students attention to increasingly consider chemical phenomena at the molecular/sub-micro level. Additionally, she asked students not to use the textbook until toward the end of the equilibrium unit and sought to engage them in using their prior knowledge of chemistry to understand their observations from experiments. Frances' changed pedagogy elicited metacognitive experiences and reflection in students and challenged them to reconsider their metacognitive beliefs about learning chemistry and how it might be achieved. While teacher change is essential for science education reform, students are not passive players in change efforts and they need to be convinced of the viability of teacher pedagogical change in the context of their goals, intentions, and beliefs.

The promise of molecular epidemiology in defining the association between radiation and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neta, R.

2000-07-01

Molecular epidemiology involves the inclusion in epidemiologic studies of biologic measurements made at a genetic and molecular level and aims to improve the current knowledge of disease etiology and risk. One of the goals of molecular epidemiology studies of cancer is to determine the role of environmental and genetic factors in initiation and progression of malignancies and to use this knowledge to develop preventive strategies. This approach promises extraordinary opportunities for revolutionizing the practice of medicine and reducing risk. However, this will be accompanied by the need to address and resolve many challenges, such as ensuring the appropriate interpretation ofmore » molecular testing and resolving associated ethical, legal, and social issues. Traditional epidemiologic approaches determined that exposure to ionizing radiation poses significantly increased risk of leukemia and several other types of cancer. Such studies provided the basis for setting exposure standards to protect the public and the workforce from potentially adverse effects of ionizing radiation. These standards were set by using modeling approaches to extrapolate from the biological effects observed in high-dose radiation studies to predicted, but mostly immeasurable, effects at low radiation doses. It is anticipated that the addition of the molecular parameters to the population-based studies will help identify the genes and pathways characteristic of cancers due to radiation exposure of individuals, as well as identify susceptible or resistant subpopulations. In turn, the information about the molecular mechanisms should aid to improve risk assessment. While studies on radiogenic concerns are currently limited to only a few candidate genes, the exponential growth of scientific knowledge and technology promises expansion of knowledge about identity of participating genes and pathways in the future. This article is meant to provide an introductory overview of recent advances in understanding of carcinogenesis at the molecular level, with an emphasis of the aspects that may be of use in establishing the association between radiation and cancer.« less

Structural definition of the BIL and DL: a new universal methodology to rationalize non-linear χ(2)(ω) SFG signals at charged interfaces, including χ(3)(ω) contributions.

PubMed

Pezzotti, Simone; Galimberti, Daria Ruth; Shen, Y Ron; Gaigeot, Marie-Pierre

2018-02-14

This work provides unambiguous definitions from theoretical simulations of the two interfacial regions named the BIL (binding interfacial layer) and DL (diffuse layer) at charged solid/water and air/water interfaces. The BIL and DL nomenclature follows the pioneering work of Wen et al. [Phys. Rev. Lett. 2016, 116, 016101]. Our definitions are based on the intrinsic structural properties of water only. Knowing the BIL and DL interfacial regions, one is then able to deconvolve the χ (2) (ω) non-linear SFG (sum frequency generation) response into χ(ω) and χ(ω) contributions, thus providing a detailed molecular interpretation of these signals and of the measured total SFG. We furthermore show that the χ(ω) spectrum arises from the χ (3) (ω) non-linear third order contribution of bulk liquid water, here calculated for several charged interfaces and shown to be universal. The χ(ω) contribution therefore has the same origin in terms of molecular normal modes at any charged interface. The molecular interpretation of χ(ω) is hence at the heart of the unambiguous molecular comprehension and interpretation of the measured total SFG signal at any charged interface.

Application of the weibull distribution function to the molecular weight distribution of cellulose

Treesearch

A. Broido; Hsiukang Yow

1977-01-01

The molecular weight distribution of a linear homologous polymer is usually obtained empirically for any particular sample. Sample-to-sample comparisons are made in terms of the weight- or number-average molecular weights and graphic displays of the distribution curves. Such treatment generally precludes data interpretations in which a distribution can be described in...

Impact of Professional Learning on Teachers' Representational Strategies and Students' Cognitive Engagement with Molecular Genetics Concepts

ERIC Educational Resources Information Center

Nichols, Kim

2018-01-01

A variety of practices and specialised representational systems are required to understand, communicate and construct molecular genetics knowledge. This study describes teachers' use of multimodal representations of molecular genetics concepts and how their strategies and choice of resources were interpreted, understood and used by students to…

Calculation of the vibrational spectra of betaine hydrochloride

NASA Astrophysics Data System (ADS)

Szafran, Miroslaw; Koput, Jacek

1997-02-01

The molecular geometries of betaine hydrochloride, BET·HCl, and free protonated betaine, BET·H +, were calculated with the 6-31G(d,p) basis set at the SCF, MP2 and DFT levels of theory. At the SCF level, the minimum energy corresponds to the ionic pair, B +Htctdot;A -, however, the equilibrium Otctdot;Cl distance is 0.14 Å shorter than the X-ray value. Inclusion of the correlation effects, both at the MP2 and DFT levels, predicts a minimum energy for the molecular complex, Btctdot;H-A, with the equilibrium Otctdot;Cl distance close to the experimental value. The frequencies and intensities of the vibrational bands of BET·HCl, BET·DCl and BET·H + were calculated at the SCF and DFT levels and compared with the solid IR spectra. All measured IR bands were interpreted in term of the calculated vibrational modes. The rms deviations between the experimental and calculated SCF frequencies were 21 and 29 cm -1 for BET·HCl and BET·DCl, respectively. The computed band intensities agree qualitatively with the experimental data. The coupling of the CO stretching and OH bending modes are discussed. The summation bands are probably enhanced in intensity by Fermi resonance with the fundamentals responsible for the main ν(OH) (ν(OD) absorption region.

Utility of Classical α-Taxonomy for Biodiversity of Aquatic Nematodes

PubMed Central

Decraemer, Wilfrida; Backeljau, Thierry

2015-01-01

“Classical α-taxonomy” has different interpretations. Therefore, within the framework of an integrated taxonomic approach it is not relevant to divide taxonomy in different components, each being allocated a different weight of importance. Preferably, taxonomy should be seen in a holistic way, including the act of delimiting and describing taxa, based on different features and available methods, and taxonomy can not be interpreted without looking at evolutionary relationships. The concept of diversity itself is quite diverse as is the measure of diversity. Taxonomic descriptions of free-living aquatic nematodes are very valuable as they provide basic phenotypic information that is necessary for the functional ecological, behavioral, and evolutionary interpretation of data gathered from molecular analyses and of the organism as a whole. In general, molecular taxonomic analyses have the advantage of being much faster and of being able to deal with a larger number of specimens but also possess the important advantage of dealing with a huge amount of features compared to the morphology-based approach. However, just as morphological studies, molecular analyses deal only with partial of an organism. PMID:25861112

Influence of molecular clustering on the interpretation of diffractograms of hydrocarbon films from tokamak T-10

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neverov, V. S., E-mail: vs-never@hotmail.com; Voloshinov, V. V., E-mail: vladimir.voloshinov@gmail.com; Kukushkin, A. B., E-mail: kukushkin-ab@nrcki.ru

2015-12-15

The influence of molecular clustering on the formerly suggested interpretation of diffraction patterns of hydrocarbon films formed in the vacuum vessel of the tokamak T-10 is analyzed numerically. The simulation of clustering of simple hydrocarbon molecules C(D, H){sub 4}, C{sub 2}(D, H){sub 4}, and C{sub 6}(D, H){sub 6} and molecules composed of curved graphene (fullerenes and toroidal nanotubes) is carried out with the rigid body molecular dynamics method. It is shown that formerly neglected atomic correlations C–C and C–D(H) in the amorphous hydrocarbon component decrease the calculated values of the scattered intensity in the range of scattering vector modulus 5more » < q < 20 nm{sup –1} because of homogenization of scatters on the spatial scale of ∼1 nm. The allowance for these correlations does not change the diffraction patterns in the range q > 20 nm{sup –1}. The results suggest the necessity to introduce to the procedure of determining the structural content of the films, similar to those from the tokamak T-10, the clusters formed by the van der Waals adhesion of hydrocarbon molecules to “graphene” nanoparticles. This simplifies the mathematical optimization to the former level of complexity—but for an extended ensemble of objects—and makes it possible to calculate the diffraction patterns of these objects using the distributed computing resources. A modified algorithm of structural content identification on the basis of joint X-ray and neutron diffractometry is suggested.« less

Dynamic changes of RNA-sequencing expression for precision medicine: N-of-1-pathways Mahalanobis distance within pathways of single subjects predicts breast cancer survival

PubMed Central

Piegorsch, Walter W.; Lussier, Yves A.

2015-01-01

Motivation: The conventional approach to personalized medicine relies on molecular data analytics across multiple patients. The path to precision medicine lies with molecular data analytics that can discover interpretable single-subject signals (N-of-1). We developed a global framework, N-of-1-pathways, for a mechanistic-anchored approach to single-subject gene expression data analysis. We previously employed a metric that could prioritize the statistical significance of a deregulated pathway in single subjects, however, it lacked in quantitative interpretability (e.g. the equivalent to a gene expression fold-change). Results: In this study, we extend our previous approach with the application of statistical Mahalanobis distance (MD) to quantify personal pathway-level deregulation. We demonstrate that this approach, N-of-1-pathways Paired Samples MD (N-OF-1-PATHWAYS-MD), detects deregulated pathways (empirical simulations), while not inflating false-positive rate using a study with biological replicates. Finally, we establish that N-OF-1-PATHWAYS-MD scores are, biologically significant, clinically relevant and are predictive of breast cancer survival (P < 0.05, n = 80 invasive carcinoma; TCGA RNA-sequences). Conclusion: N-of-1-pathways MD provides a practical approach towards precision medicine. The method generates the magnitude and the biological significance of personal deregulated pathways results derived solely from the patient’s transcriptome. These pathways offer the opportunities for deriving clinically actionable decisions that have the potential to complement the clinical interpretability of personal polymorphisms obtained from DNA acquired or inherited polymorphisms and mutations. In addition, it offers an opportunity for applicability to diseases in which DNA changes may not be relevant, and thus expand the ‘interpretable ‘omics’ of single subjects (e.g. personalome). Availability and implementation: http://www.lussierlab.net/publications/N-of-1-pathways. Contact: yves@email.arizona.edu or piegorsch@math.arizona.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26072495

Distinguishing Man from Molecules: The Distinctiveness of Medical Concepts at Different Levels of Description

PubMed Central

Cole, William G.; Michael, Patricia; Blois, Marsden S.

1987-01-01

A computer program was created to use information about the statistical distribution of words in journal abstracts to make probabilistic judgments about the level of description (e.g. molecular, cell, organ) of medical text. Statistical analysis of 7,409 journal abstracts taken from three medical journals representing distinct levels of description revealed that many medical words seem to be highly specific to one or another level of description. For example, the word adrenoreceptors occurred only in the American Journal of Physiology, never in Journal of Biological Chemistry or in Journal of American Medical Association. Such highly specific words occured so frequently that the automatic classification program was able to classify correctly 45 out of 45 test abstracts, with 100% confidence. These findings are interpreted in terms of both a theory of the structure of medical knowledge and the pragmatics of automatic classification.

Understanding allosteric interactions in G protein-coupled receptors using Supervised Molecular Dynamics: A prototype study analysing the human A3 adenosine receptor positive allosteric modulator LUF6000.

PubMed

Deganutti, Giuseppe; Cuzzolin, Alberto; Ciancetta, Antonella; Moro, Stefano

2015-07-15

The search for G protein-coupled receptors (GPCRs) allosteric modulators represents an active research field in medicinal chemistry. Allosteric modulators usually exert their activity only in the presence of the orthosteric ligand by binding to protein sites topographically different from the orthosteric cleft. They therefore offer potentially therapeutic advantages by selectively influencing tissue responses only when the endogenous agonist is present. The prediction of putative allosteric site location, however, is a challenging task. In facts, they are usually located in regions showing more structural variation among the family members. In the present work, we applied the recently developed Supervised Molecular Dynamics (SuMD) methodology to interpret at the molecular level the positive allosteric modulation mediated by LUF6000 toward the human adenosine A3 receptor (hA3 AR). Our data suggest at least two possible mechanisms to explain the experimental data available. This study represent, to the best of our knowledge, the first case reported of an allosteric recognition mechanism depicted by means of molecular dynamics simulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Experimental and theoretical spectroscopic studies of anticancer drug rosmarinic acid using HF and density functional theory.

PubMed

Mariappan, G; Sundaraganesan, N; Manoharan, S

2012-11-01

In this work, we reported a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of anticancer drug of rosmarinic acid. The optimized molecular structure, atomic charges, vibrational frequencies, natural bond orbital analysis and ultraviolet-visible spectral interpretation of rosmarinic acid have been studied by performing HF and DFT/B3LYP/6-31G(d,p) level of theory. The FT-IR (solid and solution phase), FT-Raman (solid phase) spectra were recorded in the region 4000-400 and 3500-50 cm(-1), respectively. The UV-Visible absorption spectra of the compound that dissolved in ethanol were recorded in the range of 200-800 nm. The scaled wavenumbers are compared with the experimental values. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The formation of hydrogen bond was investigated in terms of the charge density by the NBO calculations. Based on the UV spectra and TD-DFT calculations, the electronic structure and the assignments of the absorption bands were carried out. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis were investigated using theoretical calculations. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

NASA Astrophysics Data System (ADS)

Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

2016-07-01

The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of peptide conformations. These findings are consistent with experimental results, and give a molecular level interpretation for the reduced cytotoxicity of Vpr13-33 to some extent upon graphene exposure. Meanwhile, this study provides some significant insights into the detailed mechanism of graphene-induced protein conformation transition.

Envelope molecular-orbital theory of extended systems. I. Electronic states of organic quasilinear nanoheterostructures

NASA Astrophysics Data System (ADS)

Arce, J. C.; Perdomo-Ortiz, A.; Zambrano, M. L.; Mujica-Martínez, C.

2011-03-01

A conceptually appealing and computationally economical course-grained molecular-orbital (MO) theory for extended quasilinear molecular heterostructures is presented. The formalism, which is based on a straightforward adaptation, by including explicitly the vacuum, of the envelope-function approximation widely employed in solid-state physics leads to a mapping of the three-dimensional single-particle eigenvalue equations into simple one-dimensional hole and electron Schrödinger-like equations with piecewise-constant effective potentials and masses. The eigenfunctions of these equations are envelope MO's in which the short-wavelength oscillations present in the full MO's, associated with the atomistic details of the molecular potential, are smoothed out automatically. The approach is illustrated by calculating the envelope MO's of high-lying occupied and low-lying virtual π states in prototypical nanometric heterostructures constituted by oligomers of polyacetylene and polydiacetylene. Comparison with atomistic electronic-structure calculations reveals that the envelope-MO energies agree very well with the energies of the π MO's and that the envelope MO's describe precisely the long-wavelength variations of the π MO's. This envelope MO theory, which is generalizable to extended systems of any dimensionality, is seen to provide a useful tool for the qualitative interpretation and quantitative prediction of the single-particle quantum states in mesoscopic molecular structures and the design of nanometric molecular devices with tailored energy levels and wavefunctions.

A model of aging as accumulated damage matches observed mortality patterns and predicts the life-extending effects of prospective interventions

PubMed Central

Phoenix, Chris

2007-01-01

The relative insensitivity of lifespan to environmental factors constitutes compelling evidence that the physiological decline associated with aging derives primarily from the accumulation of intrinsic molecular and cellular side-effects of metabolism. Here we model that accumulation starting from a biologically based interpretation of the way in which those side-effects interact. We first validate this model by showing that it very accurately reproduces the distribution of ages at death seen in typical populations that are well protected from age-independent causes of death. We then exploit the mechanistic basis of this model to explore the impact on lifespans of interventions that combat aging, with an emphasis on interventions that repair (rather than merely retard) the direct molecular or cellular consequences of metabolism and thus prevent them from accumulating to pathogenic levels. Our results strengthen the case that an indefinite extension of healthy and total life expectancy can be achieved by a plausible rate of progress in the development of such therapies, once a threshold level of efficacy of those therapies has been reached. PMID:19424837

The Human Blood Metabolome-Transcriptome Interface

PubMed Central

Schramm, Katharina; Adamski, Jerzy; Gieger, Christian; Herder, Christian; Carstensen, Maren; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Strauch, Konstantin; Suhre, Karsten; Kastenmüller, Gabi; Prokisch, Holger; Theis, Fabian J.

2015-01-01

Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the ‘human blood metabolome-transcriptome interface’ (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease. PMID:26086077

Visualizing electron dynamics in organic materials: Charge transport through molecules and angular resolved photoemission

NASA Astrophysics Data System (ADS)

Kümmel, Stephan

Being able to visualize the dynamics of electrons in organic materials is a fascinating perspective. Simulations based on time-dependent density functional theory allow to realize this hope, as they visualize the flow of charge through molecular structures in real-space and real-time. We here present results on two fundamental processes: Photoemission from organic semiconductor molecules and charge transport through molecular structures. In the first part we demonstrate that angular resolved photoemission intensities - from both theory and experiment - can often be interpreted as a visualization of molecular orbitals. However, counter-intuitive quantum-mechanical electron dynamics such as emission perpendicular to the direction of the electrical field can substantially alter the picture, adding surprising features to the molecular orbital interpretation. In a second study we calculate the flow of charge through conjugated molecules. The calculations show in real time how breaks in the conjugation can lead to a local buildup of charge and the formation of local electrical dipoles. These can interact with neighboring molecular chains. As a consequence, collections of ''molecular electrical wires'' can show distinctly different characteristics than ''classical electrical wires''. German Science Foundation GRK 1640.

Students' Use of Three Different Visual Representations to Interpret Whether Molecules Are Polar or Nonpolar

ERIC Educational Resources Information Center

Host, Gunnar E.; Schonborn, Konrad J.; Palmerius, Karljohan E. Lundin

2012-01-01

Visualizing molecular properties is often crucial for constructing conceptual understanding in chemistry. However, research has revealed numerous challenges surrounding students' meaningful interpretation of the relationship between the geometry and electrostatic properties of molecules. This study explored students' (n = 18) use of three visual…

Critical data-based re-evaluation of minocycline as a putative specific microglia inhibitor.

PubMed

Möller, Thomas; Bard, Frédérique; Bhattacharya, Anindya; Biber, Knut; Campbell, Brian; Dale, Elena; Eder, Claudia; Gan, Li; Garden, Gwenn A; Hughes, Zoë A; Pearse, Damien D; Staal, Roland G W; Sayed, Faten A; Wes, Paul D; Boddeke, Hendrikus W G M

2016-10-01

Minocycline, a second generation broad-spectrum antibiotic, has been frequently postulated to be a "microglia inhibitor." A considerable number of publications have used minocycline as a tool and concluded, after achieving a pharmacological effect, that the effect must be due to "inhibition" of microglia. It is, however, unclear how this "inhibition" is achieved at the molecular and cellular levels. Here, we weigh the evidence whether minocycline is indeed a bona fide microglia inhibitor and discuss how data generated with minocycline should be interpreted. GLIA 2016;64:1788-1794. © 2016 Wiley Periodicals, Inc.

Hypothesis driven single cell dual oscillator mathematical model of circadian rhythms

PubMed Central

S, Shiju

2017-01-01

Molecular mechanisms responsible for 24 h circadian oscillations, entrainment to external cues, encoding of day length and the time-of-day effects have been well studied experimentally. However, it is still debated from the molecular network point of view whether each cell in suprachiasmatic nuclei harbors two molecular oscillators, where one tracks dawn and the other tracks dusk activities. A single cell dual morning and evening oscillator was proposed by Daan et al., based on the molecular network that has two sets of similar non-redundant per1/cry1 and per2/cry2 circadian genes and each can independently maintain their endogenous oscillations. Understanding of dual oscillator dynamics in a single cell at molecular level may provide insight about the circadian mechanisms that encodes day length variations and its response to external zeitgebers. We present here a realistic dual oscillator model of circadian rhythms based on the series of hypotheses proposed by Daan et al., in which they conjectured that the circadian genes per1/cry1 track dawn while per2/cry2 tracks dusk and they together constitute the morning and evening oscillators (dual oscillator). Their hypothesis also provides explanations about the encoding of day length in terms of molecular mechanisms of per/cry expression. We frame a minimal mathematical model with the assumption that per1 acts a morning oscillator and per2 acts as an evening oscillator and to support and interpret this assumption we fit the model to the experimental data of per1/per2 circadian temporal dynamics, phase response curves (PRC's), and entrainment phenomena under various light-dark conditions. We also capture different patterns of splitting phenomena by coupling two single cell dual oscillators with neuropeptides vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) as the coupling agents and provide interpretation for the occurrence of splitting in terms of ME oscillators, though they are not required to explain the morning and evening oscillators. The proposed dual oscillator model based on Daan's hypothesis supports per1 and per2 playing the role of morning and evening oscillators respectively and this may be the first step towards the understanding of the core molecular mechanism responsible for encoding the day length. PMID:28486525

Hypothesis driven single cell dual oscillator mathematical model of circadian rhythms.

PubMed

S, Shiju; Sriram, K

2017-01-01

Molecular mechanisms responsible for 24 h circadian oscillations, entrainment to external cues, encoding of day length and the time-of-day effects have been well studied experimentally. However, it is still debated from the molecular network point of view whether each cell in suprachiasmatic nuclei harbors two molecular oscillators, where one tracks dawn and the other tracks dusk activities. A single cell dual morning and evening oscillator was proposed by Daan et al., based on the molecular network that has two sets of similar non-redundant per1/cry1 and per2/cry2 circadian genes and each can independently maintain their endogenous oscillations. Understanding of dual oscillator dynamics in a single cell at molecular level may provide insight about the circadian mechanisms that encodes day length variations and its response to external zeitgebers. We present here a realistic dual oscillator model of circadian rhythms based on the series of hypotheses proposed by Daan et al., in which they conjectured that the circadian genes per1/cry1 track dawn while per2/cry2 tracks dusk and they together constitute the morning and evening oscillators (dual oscillator). Their hypothesis also provides explanations about the encoding of day length in terms of molecular mechanisms of per/cry expression. We frame a minimal mathematical model with the assumption that per1 acts a morning oscillator and per2 acts as an evening oscillator and to support and interpret this assumption we fit the model to the experimental data of per1/per2 circadian temporal dynamics, phase response curves (PRC's), and entrainment phenomena under various light-dark conditions. We also capture different patterns of splitting phenomena by coupling two single cell dual oscillators with neuropeptides vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) as the coupling agents and provide interpretation for the occurrence of splitting in terms of ME oscillators, though they are not required to explain the morning and evening oscillators. The proposed dual oscillator model based on Daan's hypothesis supports per1 and per2 playing the role of morning and evening oscillators respectively and this may be the first step towards the understanding of the core molecular mechanism responsible for encoding the day length.

Ligand-Induced Energy Shift and Localization of Kondo Resonances in Cobalt-Based Complexes on Cu(111).

PubMed

Knaak, Thomas; Gruber, Manuel; Lindström, Christoph; Bocquet, Marie-Laure; Heck, Jürgen; Berndt, Richard

2017-11-08

Magnetic sandwich complexes are of particular interest for molecular spintronics. Using scanning tunneling microscopy, we evidence the successful deposition of 1,3,5-tris(η 6 -borabenzene-η 5 -cyclopentadienylcobalt) benzene, a molecule composed of three connected magnetic sandwich units, on Cu(111). Scanning tunneling spectra reveal two distinct spatial-dependent narrow resonances close to the Fermi level for the trimer molecules as well as for molecular fragments composed of one and two magnetic units. With the help of density functional theory, these resonances are interpreted as two Kondo resonances originating from two distinct nondegenerate d-like orbitals. These Kondo resonances are found to have defined spatial extents dictated by the hybridization of the involved orbitals with that of the ligands. These results opens promising perspectives for investigating complex Kondo systems composed of several "Kondo" orbitals.

qPCR for second year undergraduates: A short, structured inquiry to illustrate differential gene expression.

PubMed

McCauslin, Christine Seitz; Gunn, Kathryn Elaine; Pirone, Dana; Staiger, Jennifer

2015-01-01

We describe a structured inquiry laboratory exercise that examines transcriptional regulation of the NOS2 gene under conditions that simulate the inflammatory response in macrophages. Using quantitative PCR and the comparative CT method, students are able determine whether transcriptional activation of NOS2 occurs and to what degree. The exercise is aimed at second year undergraduates who possess basic knowledge of gene expression events. It requires only 4-5 hr of dedicated laboratory time and focuses on use of the primary literature, data analysis, and interpretation. Importantly, this exercise provides a mechanism to introduce the concept of differential gene expression and provides a starting point for development of more complex guided or open inquiry projects for students moving into upper level molecular biology, immunology, and biochemistry course work. © 2015 The International Union of Biochemistry and Molecular Biology.

State-of-the-art radiation detectors for medical imaging: Demands and trends

NASA Astrophysics Data System (ADS)

Darambara, Dimitra G.

2006-12-01

Over the last half-century a variety of significant technical advances in several scientific fields has been pointing to an exploding growth in the field of medical imaging leading to a better interpretation of more specific anatomical, biochemical and molecular pathways. In particular, the development of novel imaging detectors and readout electronics has been critical to the advancement of medical imaging allowing the invention of breakthrough platforms for simultaneous acquisition of multi-modality images at molecular level. The present paper presents a review of the challenges, demands and constraints on radiation imaging detectors imposed by the nature of the modality and the physics of the imaging source. This is followed by a concise review and perspective on various types of state-of-the-art detector technologies that have been developed to meet these requirements. Trends, prospects and new concepts for future imaging detectors are also highlighted.

An ab initio study of some binary complexes containing methyl fluoride and difluoromethane: red-shifting and blue-shifting hydrogen bonds

NASA Astrophysics Data System (ADS)

Ramasami, Ponnadurai; Ford, Thomas A.

2018-07-01

The properties of a number of hydrogen-bonded complexes of methyl fluoride and difluoromethane with a range of hydrides of the first two rows of the periodic table have been computed using ab initio molecular orbital theory. The aim of this work was to identify possible examples of blue-shifting hydrogen-bonded species analogous to those formed between fluoroform and ammonia, water, phosphine and hydrogen sulphide, reported earlier. The calculations were carried out using the Gaussian-09 program, at the second-order level of Møller-Plesset perturbation theory, and with the aug-cc-pVTZ basis sets of Dunning. The properties studied include the molecular structures, the hydrogen bond energies and the vibrational spectra. The results have been interpreted with the aid of natural bond orbital theory and the quantum theory of atoms in molecules.

Dark-field-based observation of single-nanoparticle dynamics on a supported lipid bilayer for in situ analysis of interacting molecules and nanoparticles.

PubMed

Lee, Young Kwang; Kim, Sungi; Nam, Jwa-Min

2015-01-12

Observation of single plasmonic nanoparticles in reconstituted biological systems allows us to obtain snapshots of dynamic processes between molecules and nanoparticles with unprecedented spatiotemporal resolution and single-molecule/single-particle-level data acquisition. This Concept is intended to introduce nanoparticle-tethered supported lipid bilayer platforms that allow for the dynamic confinement of nanoparticles on a two-dimensional fluidic surface. The dark-field-based long-term, stable, real-time observation of freely diffusing plasmonic nanoparticles on a lipid bilayer enables one to extract a broad range of information about interparticle and molecular interactions throughout the entire reaction period. Herein, we highlight important developments in this context to provide ideas on how molecular interactions can be interpreted by monitoring dynamic behaviors and optical signals of laterally mobile nanoparticles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New technologies for the human cytome project.

PubMed

Tárnok, A

2004-01-01

Cytomes or cell systems are composed of various kinds of single-cells and constitute the elementary building units of organs and organisms. Their individualised (cytomic) analysis overcomes the problem of averaged results from cell and tissue homogenates where molecular changes in low frequency cell populations may be hidden and wrongly interpreted. Analysis of the cytome is of pivotal importance in basic research for the understanding of cells and their interrelations in complex environments like tissues and in predictive medicine where it is a prerequisite for individualised preventive therapy. Analysis of molecular phenotypes requires instrumentation that on the one hand provides high-throughput measurement of individual cells and is on the other hand highly multiplexed, enabling the simultaneous acquisition of many parameters on the single cell level. Upcoming technology suitable to this task, such as slide based cytometry is available or under development. The realisation of cytomic technology is important for the realisation of the human cytome project.

Simulations of single-particle imaging of hydrated proteins with x-ray free-electron lasers

NASA Astrophysics Data System (ADS)

Fortmann-Grote, C.; Bielecki, J.; Jurek, Z.; Santra, R.; Ziaja-Motyka, B.; Mancuso, A. P.

2017-08-01

We employ start-to-end simulations to model coherent diffractive imaging of single biomolecules using x-ray free electron lasers. This technique is expected to yield new structural information about biologically relevant macromolecules thanks to the ability to study the isolated sample in its natural environment as opposed to crystallized or cryogenic samples. The effect of the solvent on the diffraction pattern and interpretability of the data is an open question. We present first results of calculations where the solvent is taken into account explicitly. They were performed with a molecular dynamics scheme for a sample consisting of a protein and a hydration layer of varying thickness. Through R-factor analysis of the simulated diffraction patterns from hydrated samples, we show that the scattering background from realistic hydration layers of up to 3 Å thickness presents no obstacle for the resolution of molecular structures at the sub-nm level.

Multiplex Molecular Panels for Diagnosis of Gastrointestinal Infection: Performance, Result Interpretation, and Cost-Effectiveness.

PubMed

Binnicker, Matthew J

2015-12-01

Gastrointestinal disease is a major cause of morbidity and mortality worldwide, especially among young children and immunocompromised patients. Diarrhea may result from infection with a variety of microbial pathogens, including bacteria, viruses, or parasites. Historically, the diagnosis of infectious diarrhea has been made using microscopy, antigen tests, culture, and real-time PCR. A combination of these traditional tests is often required due to the inability to distinguish between infectious etiologies based on the clinical presentation alone. Recently, several multiplex molecular assays have been developed for the detection of gastrointestinal pathogens directly from clinical stool samples. These panels allow for the detection and identification of up to 20 pathogens in as little as 1 h. This review will focus on the multiplex molecular panels that have received clearance from the FDA for the diagnosis of diarrheal disease and will highlight issues related to test performance, result interpretation, and cost-effectiveness of these new molecular diagnostic tools.

Reader Training for the Restaging of Biochemically Recurrent Prostate Cancer Using 18F-Fluciclovine PET/CT.

PubMed

Miller, Matthew P; Kostakoglu, Lale; Pryma, Daniel; Yu, Jian Qin; Chau, Albert; Perlman, Eric; Clarke, Bonnie; Rosen, Donald; Ward, Penelope

2017-10-01

18 F-Fluciclovine is a novel PET/CT tracer. This blinded image evaluation (BIE) sought to demonstrate that, after limited training, readers naïve to 18 F-fluciclovine could interpret 18 F-fluciclovine images from subjects with biochemically recurrent prostate cancer with acceptable diagnostic performance and reproducibility. The primary objectives were to establish individual readers' diagnostic performance and the overall interpretation (2/3 reader concordance) compared with standard-of-truth data (histopathology or clinical follow-up) and to evaluate interreader reproducibility. Secondary objectives included comparison to the expert reader and assessment of intrareader reproducibility. Methods: 18 F-Fluciclovine PET/CT images ( n = 121) and corresponding standard-of-truth data were collected from 110 subjects at Emory University using a single-time-point static acquisition starting 5 min after injection of approximately 370 MBq of 18 F-fluciclovine. Three readers were trained using standardized interpretation methodology and subsequently evaluated the images in a blinded manner. Analyses were conducted at the lesion, region (prostate, including bed and seminal vesicle, or extraprostatic, including all lymph nodes, bone, or soft-tissue metastasis), and subject level. Results: Lesion-level overall positive predictive value was 70.5%. The readers' positive predictive value and negative predictive value were broadly consistent with each other and with the onsite read. Sensitivity was highest for readers 1 and 2 (68.5% and 63.9%, respectively) whereas specificity was highest for reader 3 (83.6%). Overall, prostate-level sensitivity was high (91.4%), but specificity was moderate (48.7%). Interreader agreement was 94.7%, 74.4%, and 70.3% for the lesion, prostate, and extraprostatic levels, respectively, with associated Fleiss' κ-values of 0.54, 0.50, and 0.57. Intrareader agreement was 97.8%, 96.9%, and 99.1% at the lesion level; 100%, 100%, and 91.7% in the prostate region; and 83.3%, 75.0%, and 83.3% in the extraprostatic region for readers 1, 2, and 3, respectively. Concordance between the BIE and the onsite reader exceeded 75% for each reader at the lesion, region, and subject levels. Conclusion: Specific training in the use of standardized interpretation methodology for assessment of 18 F-fluciclovine PET/CT images enables naïve readers to achieve acceptable diagnostic performance and reproducibility when staging recurrent prostate cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Hydrogen Donor-Acceptor Fluctuations from Kinetic Isotope Effects: A Phenomenological Model

PubMed Central

Roston, Daniel; Cheatum, Christopher M.; Kohen, Amnon

2012-01-01

Kinetic isotope effects (KIEs) and their temperature dependence can probe the structural and dynamic nature of enzyme-catalyzed proton or hydride transfers. The molecular interpretation of their temperature dependence requires expensive and specialized QM/MM calculations to provide a quantitative molecular understanding. Currently available phenomenological models use a non-adiabatic assumption that is not appropriate for most hydride and proton-transfer reactions, while others require more parameters than the experimental data justify. Here we propose a phenomenological interpretation of KIEs based on a simple method to quantitatively link the size and temperature dependence of KIEs to a conformational distribution of the catalyzed reaction. The present model assumes adiabatic hydrogen tunneling, and by fitting experimental KIE data, the model yields a population distribution for fluctuations of the distance between donor and acceptor atoms. Fits to data from a variety of proton and hydride transfers catalyzed by enzymes and their mutants, as well as non-enzymatic reactions, reveal that steeply temperature-dependent KIEs indicate the presence of at least two distinct conformational populations, each with different kinetic behaviors. We present the results of these calculations for several published cases and discuss how the predictions of the calculations might be experimentally tested. The current analysis does not replace molecular quantum mechanics/molecular mechanics (QM/MM) investigations, but it provides a fast and accessible way to quantitatively interpret KIEs in the context of a Marcus-like model. PMID:22857146

Changes in Chromatin Compaction During the Cell Cycle Revealed by Micrometer-Scale Measurement of Molecular Flow in the Nucleus

PubMed Central

Hinde, Elizabeth; Cardarelli, Francesco; Digman, Michelle A.; Gratton, Enrico

2012-01-01

We present a quantitative fluctuation-based assay to measure the degree of local chromatin compaction and investigate how chromatin density regulates the diffusive path adopted by an inert protein in dividing cells. The assay uses CHO-K1 cells coexpressing untagged enhanced green fluorescent protein (EGFP) and histone H2B tagged mCherry. We measure at the single-cell level the EGFP localization and molecular flow patterns characteristic of each stage of chromatin compaction from mitosis through interphase by means of pair-correlation analysis. We find that the naturally occurring changes in chromatin organization impart a regulation on the spatial distribution and temporal dynamics of EGFP within the nucleus. Combined with the analysis of Ca2+ intracellular homeostasis during cell division, EGFP flow regulation can be interpreted as the result of controlled changes in chromatin compaction. For the first time, to our knowledge, we were able to probe chromatin compaction on the micrometer scale, where the regulation of molecular diffusion may become relevant for many cellular processes. PMID:22325293

Molecular structure, spectral studies, NBO, HOMO-LUMO profile, MEP and Mulliken analysis of 3β,6β-dichloro-5α-hydroxy-5α-cholestane

NASA Astrophysics Data System (ADS)

Alam, Mahboob; Park, Soonheum

2018-05-01

The synthesis of 3β,6β-dichloro-5α-hydroxy-5α-cholestane (in general, steroidal chlorohydrin or steroidal halohydrin) and theoretical study of the structure are reported in this paper. The individuality of chlorohydrin was confirmed by FT-IR, NMR, MS, CHN microanalysis and X-ray crystallography. DFT calculations on the titled molecule have been performed. The molecular structure and spectra explained by Gaussian hybrid computational analysis theory (B3LYP) are found to be in correlation with the experimental data obtained from the various spectrophotometric techniques. The theoretical geometry optimization data were compared with the X-ray data. The vibrational bands appearing in the FT-IR are assigned with accuracy using harmonic frequencies along with intensities and animated modes. Molecular properties like NBO, HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping and dipole moment have been dealt at same level of theory. The calculated electronic spectrum of chlorohydrin is interpreted on the basis of TD-DFT calculations.

Modeling Protein Expression and Protein Signaling Pathways

PubMed Central

Telesca, Donatello; Müller, Peter; Kornblau, Steven M.; Suchard, Marc A.; Ji, Yuan

2015-01-01

High-throughput functional proteomic technologies provide a way to quantify the expression of proteins of interest. Statistical inference centers on identifying the activation state of proteins and their patterns of molecular interaction formalized as dependence structure. Inference on dependence structure is particularly important when proteins are selected because they are part of a common molecular pathway. In that case, inference on dependence structure reveals properties of the underlying pathway. We propose a probability model that represents molecular interactions at the level of hidden binary latent variables that can be interpreted as indicators for active versus inactive states of the proteins. The proposed approach exploits available expert knowledge about the target pathway to define an informative prior on the hidden conditional dependence structure. An important feature of this prior is that it provides an instrument to explicitly anchor the model space to a set of interactions of interest, favoring a local search approach to model determination. We apply our model to reverse-phase protein array data from a study on acute myeloid leukemia. Our inference identifies relevant subpathways in relation to the unfolding of the biological process under study. PMID:26246646

Adsorption and dissociation of molecular hydrogen on orthorhombic β-Mo 2C and cubic δ-MoC (001) surfaces

DOE PAGES

Posada-Pérez, Sergio; Viñes, Francesc; Valero, Rosendo; ...

2016-10-03

Molybdenum carbides are increasingly used in heterogeneously catalyzed hydrogenation reactions, which imply the adsorption and dissociation of molecular hydrogen. In this paper, a systematic density functional theory based study, including or excluding dispersion terms, concerning the interaction and stability of H 2 with cubic δ-MoC(001) and orthorhombic β-Mo 2C(001) surfaces, is presented. In the latter case the two possible C or Mo terminations are considered. In addition, different situations for the H covered surfaces are examined. Computational results including dispersive forces predict an essentially spontaneous dissociation of H 2 on β-Mo 2C(001) independently of the surface termination, whereas on δ-MoC(001)more » molecular hydrogen dissociation implies a small but noticeable energy barrier. Furthermore, the ab initio thermodynamics formalism has been used to compare the stability of different H coverages. In conclusion, core level binding energies and vibrational frequencies are presented with the aim to assist the interpretation of yet unavailable data from X-ray photoelectron and infrared spectroscopies.« less

The role of boron nitride nanotube as a new chemical sensor and potential reservoir for hydrogen halides environmental pollutants

NASA Astrophysics Data System (ADS)

Yoosefian, Mehdi; Etminan, Nazanin; Moghani, Maryam Zeraati; Mirzaei, Samaneh; Abbasi, Shima

2016-10-01

Density functional theory (DFT) studies on the interaction of hydrogen halides (HX) environmental pollutants and the boron nitride nanotubes (BNNTs) have been reported. To exploit the possibility of BNNTs as gas sensors, the adsorption of hydrogen fluoride (HF), hydrogen chloride (HCl) and hydrogen bromide (HBr) on the side wall of armchair (5,5) boron nitride nanotubes have been investigated. B3LYP/6-31G (d) level were used to analyze the structural and electronic properties of investigate sensor. The adsorption process were interpreted by highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO), quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) and molecular electrostatic potential (MEP) analysis. Topological parameters of bond critical points have been used to calculate as measure of hydrogen bond (HB) strength. Stronger binding energy, larger charge transfer and charge density illustrate that HF gas possesses chemisorbed adsorption process. The obtained results also show the strongest HB in HF/BNNT complex. We expect that results could provide helpful information for the design of new BNNTs based sensing devices.

Hadron molecules

NASA Astrophysics Data System (ADS)

Thomas, Gutsche; Tanja, Branz; Amand, Faessler; Ian, Woo Lee; Valery, E. Lyubovitskij

2010-09-01

We discuss a possible interpretation of the open charm mesons D*s0(2317), Ds1(2460) and the hidden charm mesons X(3872), Y(3940) and Y(4140) as hadron molecules. Using a phenomenological Lagrangian approach we review the strong and radiative decays of the D*s0(2317) and Ds1(2460) states. The X(3872) is assumed to consist dominantly of molecular hadronic components with an additional small admixture of a charmonium configuration. Determing the radiative (γJ/Ψ and γΨ(2s)) and strong (J/Ψ2π and J/Ψ3π) decay modes we show that the present experimental observation is consistent with the molecular structure assumption of the X(3872). Finally, we give evidence for molecular interpretations of the Y(3940) and Y(4140) related to the observed strong decay modes J/Ψ + ω or J/Ψ + varphi, respectively.

Climate variations and the physiological basis of temperature dependent biogeography: systemic to molecular hierarchy of thermal tolerance in animals.

PubMed

Pörtner, H O

2002-08-01

The physiological mechanisms limiting and adjusting cold and heat tolerance have regained interest in the light of global warming and associated shifts in the geographical distribution of ectothermic animals. Recent comparative studies, largely carried out on marine ectotherms, indicate that the processes and limits of thermal tolerance are linked with the adjustment of aerobic scope and capacity of the whole animal as a crucial step in thermal adaptation on top of parallel adjustments at the molecular or membrane level. In accordance with Shelford's law of tolerance decreasing whole animal aerobic scope characterises the onset of thermal limitation at low and high pejus thresholds (pejus=getting worse). The drop in aerobic scope of an animal indicated by falling oxygen levels in the body fluids and or the progressively limited capacity of circulatory and ventilatory mechanisms. At high temperatures, excessive oxygen demand causes insufficient oxygen levels in the body fluids, whereas at low temperatures the aerobic capacity of mitochondria may become limiting for ventilation and circulation. Further cooling or warming beyond these limits leads to low or high critical threshold temperatures (T(c)) where aerobic scope disappears and transition to an anaerobic mode of mitochondrial metabolism and progressive insufficiency of cellular energy levels occurs. The adjustments of mitochondrial densities and their functional properties appear as a critical process in defining and shifting thermal tolerance windows. The finding of an oxygen limited thermal tolerance owing to loss of aerobic scope is in line with Taylor's and Weibel's concept of symmorphosis, which implies that excess capacity of any component of the oxygen delivery system is avoided. The present study suggests that the capacity of oxygen delivery is set to a level just sufficient to meet maximum oxygen demand between the average highs and lows of environmental temperatures. At more extreme temperatures only time limited passive survival is supported by anaerobic metabolism or the protection of molecular functions by heat shock proteins and antioxidative defence. As a corollary, the first line of thermal sensitivity is due to capacity limitations at a high level of organisational complexity, i.e. the integrated function of the oxygen delivery system, before individual, molecular or membrane functions become disturbed. These interpretations are in line with the more general consideration that, as a result of the high level of complexity of metazoan organisms compared with simple eukaryotes and then prokaryotes, thermal tolerance is reduced in metazoans. A similar sequence of sensitivities prevails within the metazoan organism, with the highest sensitivity at the organismic level and wider tolerance windows at lower levels of complexity. However, the situation is different in that loss in aerobic scope and progressive hypoxia at the organismic level define the onset of thermal limitation which then transfers to lower hierarchical levels and causes cellular and molecular disturbances. Oxygen limitation contributes to oxidative stress and, finally, denaturation or malfunction of molecular repair, e.g. during suspension of protein synthesis. The sequence of thermal tolerance limits turns into a hierarchy, ranging from systemic to cellular to molecular levels.

Trade-offs in thermal adaptation: the need for a molecular to ecological integration.

PubMed

Pörtner, Hans O; Bennett, Albert F; Bozinovic, Francisco; Clarke, Andrew; Lardies, Marco A; Lucassen, Magnus; Pelster, Bernd; Schiemer, Fritz; Stillman, Jonathon H

2006-01-01

Through functional analyses, integrative physiology is able to link molecular biology with ecology as well as evolutionary biology and is thereby expected to provide access to the evolution of molecular, cellular, and organismic functions; the genetic basis of adaptability; and the shaping of ecological patterns. This paper compiles several exemplary studies of thermal physiology and ecology, carried out at various levels of biological organization from single genes (proteins) to ecosystems. In each of those examples, trade-offs and constraints in thermal adaptation are addressed; these trade-offs and constraints may limit species' distribution and define their level of fitness. For a more comprehensive understanding, the paper sets out to elaborate the functional and conceptual connections among these independent studies and the various organizational levels addressed. This effort illustrates the need for an overarching concept of thermal adaptation that encompasses molecular, organellar, cellular, and whole-organism information as well as the mechanistic links between fitness, ecological success, and organismal physiology. For this data, the hypothesis of oxygen- and capacity-limited thermal tolerance in animals provides such a conceptual framework and allows interpreting the mechanisms of thermal limitation of animals as relevant at the ecological level. While, ideally, evolutionary studies over multiple generations, illustrated by an example study in bacteria, are necessary to test the validity of such complex concepts and underlying hypotheses, animal physiology frequently is constrained to functional studies within one generation. Comparisons of populations in a latitudinal cline, closely related species from different climates, and ontogenetic stages from riverine clines illustrate how evolutionary information can still be gained. An understanding of temperature-dependent shifts in energy turnover, associated with adjustments in aerobic scope and performance, will result. This understanding builds on a mechanistic analysis of the width and location of thermal windows on the temperature scale and also on study of the functional properties of relevant proteins and associated gene expression mechanisms.

Electrocardiography: A Technologist's Guide to Interpretation.

PubMed

Tso, Colin; Currie, Geoffrey M; Gilmore, David; Kiat, Hosen

2015-12-01

The nuclear medicine technologist works with electrocardiography when performing cardiac stress testing and gated cardiac imaging and when monitoring critical patients. To enhance patient care, basic electrocardiogram interpretation skills and recognition of key arrhythmias are essential for the nuclear medicine technologist. This article provides insight into the anatomy of an electrocardiogram trace, covers basic electrocardiogram interpretation methods, and describes an example case typical in the nuclear medicine environment. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

FINITE EXPANSION METHOD FOR THE CALCULATION AND INTERPRETATION OF MOLECULAR ELECTROSTATIC POTENTIALS

EPA Science Inventory

Because it is useful to have the molecular electrostatic potential as an element in a complex scheme to assess the toxicity of large molecules, efficient and reliable methods are needed for the calculation and characterization of these potentials. A multicenter multipole expansio...

Systems Proteomics for Translational Network Medicine

PubMed Central

Arrell, D. Kent; Terzic, Andre

2012-01-01

Universal principles underlying network science, and their ever-increasing applications in biomedicine, underscore the unprecedented capacity of systems biology based strategies to synthesize and resolve massive high throughput generated datasets. Enabling previously unattainable comprehension of biological complexity, systems approaches have accelerated progress in elucidating disease prediction, progression, and outcome. Applied to the spectrum of states spanning health and disease, network proteomics establishes a collation, integration, and prioritization algorithm to guide mapping and decoding of proteome landscapes from large-scale raw data. Providing unparalleled deconvolution of protein lists into global interactomes, integrative systems proteomics enables objective, multi-modal interpretation at molecular, pathway, and network scales, merging individual molecular components, their plurality of interactions, and functional contributions for systems comprehension. As such, network systems approaches are increasingly exploited for objective interpretation of cardiovascular proteomics studies. Here, we highlight network systems proteomic analysis pipelines for integration and biological interpretation through protein cartography, ontological categorization, pathway and functional enrichment and complex network analysis. PMID:22896016

Naval Surface Warfare Center Dahlgren Division Technical Digest. Advanced Materials Technology

DTIC Science & Technology

1993-09-01

of Prins1 2’h3 ated TL glow curve plus a contribution from and Novakov ,12 these peaks are interpreted to the phototransfer process. arise from the... Novakov , T., "X-ray Photoelectron Spectra cist in the Radiation and Molecular Orbital Interpretation of the Valence Dosimetry Group. Since Band

Characterization of a thermally imidized soluble polyimide film

NASA Technical Reports Server (NTRS)

Young, Philip R.; Davis, Judith R. J.; Chang, A. C.; Richardson, John N.

1989-01-01

A soluble aromatic poly(amic acid) film was converted to a soluble polyimide by staging at 25 deg intervals to 325 C and characterized at each interval by several analytical methods. The behavior observed was consistent with an interpretation that a reduction occurred in molecular weight of the poly(amic acid) during the initial stages of cure before the ultimate molecular weight was achieved as a polyimide. This interpretation was supported by the results of solution viscosity, gel permeation chromatography, low angle laser light scattering photometry and infrared spectroscopy analysis. The results serve to increase the fundamental understanding of how polyimides are thermally formed from poly(amic acids).

Clinical, Biomechanical, and Physiological Translational Interpretations of Human Resting Myofascial Tone or Tension

PubMed Central

Masi, Alfonse T.; Nair, Kalyani; Evans, Tyler; Ghandour, Yousef

2010-01-01

Background Myofascial tissues generate integrated webs and networks of passive and active tensional forces that provide stabilizing support and that control movement in the body. Passive [central nervous system (CNS)–independent] resting myofascial tension is present in the body and provides a low-level stabilizing component to help maintain balanced postures. This property was recently called “human resting myofascial tone” (HRMT). The HRMT model evolved from electromyography (EMG) research in the 1950s that showed lumbar muscles usually to be EMG-silent in relaxed gravity-neutral upright postures. Methods Biomechanical, clinical, and physiological studies were reviewed to interpret the passive stiffness properties of HRMT that help to stabilize various relaxed functions such as quiet balanced standing. Biomechanical analyses and experimental studies of the lumbar multifidus were reviewed to interpret its passive stiffness properties. The lumbar multifidus was illustrated as the major core stabilizing muscle of the spine, serving an important passive biomechanical role in the body. Results Research into muscle physiology suggests that passive resting tension (CNS-independent) is generated in sarcomeres by the molecular elasticity of low-level cycling cross-bridges between the actomyosin filaments. In turn, tension is complexly transmitted to intimately enveloping fascial matrix fibrils and other molecular elements in connective tissue, which, collectively, constitute the myofascial unit. Postural myofascial tonus varies with age and sex. Also, individuals in the population are proposed to vary in a polymorphism of postural HRMT. A few people are expected to have outlier degrees of innate postural hypotonicity or hypertonicity. Such biomechanical variations likely predispose to greater risk of related musculoskeletal disorders, a situation that deserves greater attention in clinical practice and research. Axial myofascial hypertonicity was hypothesized to predispose to ankylosing spondylitis. This often-progressive deforming condition of vertebrae and sacroiliac joints is characterized by stiffness features and particular localization of bony lesions at entheseal sites. Such unique features imply concentrations and transmissions of excessive force, leading to tissue micro-injury and maladaptive repair reactions. Conclusions The HRMT model is now expanded and translated for clinical relevance to therapists. Its passive role in helping to maintain balanced postures is supported by biomechanical principles of myofascial elasticity, tension, stress, stiffness, and tensegrity. Further research is needed to determine the molecular basis of HRMT in sarcomeres, the transmission of tension by the enveloping fascial elements, and the means by which the myofascia helps to maintain efficient passive postural balance in the body. Significant deficiencies or excesses of postural HRMT may predispose to symptomatic or pathologic musculoskeletal disorders whose mechanisms are currently unexplained. PMID:21589685

Metabolic modeling helps interpret transcriptomic changes during malaria.

PubMed

Tang, Yan; Gupta, Anuj; Garimalla, Swetha; Galinski, Mary R; Styczynski, Mark P; Fonseca, Luis L; Voit, Eberhard O

2018-06-01

Disease represents a specific case of malfunctioning within a complex system. Whereas it is often feasible to observe and possibly treat the symptoms of a disease, it is much more challenging to identify and characterize its molecular root causes. Even in infectious diseases that are caused by a known parasite, it is often impossible to pinpoint exactly which molecular profiles of components or processes are directly or indirectly altered. However, a deep understanding of such profiles is a prerequisite for rational, efficacious treatments. Modern omics methodologies are permitting large-scale scans of some molecular profiles, but these scans often yield results that are not intuitive and difficult to interpret. For instance, the comparison of healthy and diseased transcriptome profiles may point to certain sets of involved genes, but a host of post-transcriptional processes and regulatory mechanisms renders predictions regarding metabolic or physiological consequences of the observed changes in gene expression unreliable. Here we present proof of concept that dynamic models of metabolic pathway systems may offer a tool for interpreting transcriptomic profiles measured during disease. We illustrate this strategy with the interpretation of expression data of genes coding for enzymes associated with purine metabolism. These data were obtained during infections of rhesus macaques (Macaca mulatta) with the malaria parasite Plasmodium cynomolgi or P. coatneyi. The model-based interpretation reveals clear patterns of flux redistribution within the purine pathway that are consistent between the two malaria pathogens and are even reflected in data from humans infected with P. falciparum. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. Copyright © 2017 Elsevier B.V. All rights reserved.

Phylogeny of a genomically diverse group of elymus (poaceae) allopolyploids reveals multiple levels of reticulation.

PubMed

Mason-Gamer, Roberta J

2013-01-01

The grass tribe Triticeae (=Hordeeae) comprises only about 300 species, but it is well known for the economically important crop plants wheat, barley, and rye. The group is also recognized as a fascinating example of evolutionary complexity, with a history shaped by numerous events of auto- and allopolyploidy and apparent introgression involving diploids and polyploids. The genus Elymus comprises a heterogeneous collection of allopolyploid genome combinations, all of which include at least one set of homoeologs, designated St, derived from Pseudoroegneria. The current analysis includes a geographically and genomically diverse collection of 21 tetraploid Elymus species, and a single hexaploid species. Diploid and polyploid relationships were estimated using four molecular data sets, including one that combines two regions of the chloroplast genome, and three from unlinked nuclear genes: phosphoenolpyruvate carboxylase, β-amylase, and granule-bound starch synthase I. Four gene trees were generated using maximum likelihood, and the phylogenetic placement of the polyploid sequences reveals extensive reticulation beyond allopolyploidy alone. The trees were interpreted with reference to numerous phenomena known to complicate allopolyploid phylogenies, and introgression was identified as a major factor in their history. The work illustrates the interpretation of complicated phylogenetic results through the sequential consideration of numerous possible explanations, and the results highlight the value of careful inspection of multiple independent molecular phylogenetic estimates, with particular focus on the differences among them.

The Genomic and Transcriptomic Landscape of a HeLa Cell Line

PubMed Central

Landry, Jonathan J. M.; Pyl, Paul Theodor; Rausch, Tobias; Zichner, Thomas; Tekkedil, Manu M.; Stütz, Adrian M.; Jauch, Anna; Aiyar, Raeka S.; Pau, Gregoire; Delhomme, Nicolas; Gagneur, Julien; Korbel, Jan O.; Huber, Wolfgang; Steinmetz, Lars M.

2013-01-01

HeLa is the most widely used model cell line for studying human cellular and molecular biology. To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome. Effective design and interpretation of molecular genetic studies performed using HeLa cells require accurate genomic information. Here we present a detailed genomic and transcriptomic characterization of a HeLa cell line. We performed DNA and RNA sequencing of a HeLa Kyoto cell line and analyzed its mutational portfolio and gene expression profile. Segmentation of the genome according to copy number revealed a remarkably high level of aneuploidy and numerous large structural variants at unprecedented resolution. Some of the extensive genomic rearrangements are indicative of catastrophic chromosome shattering, known as chromothripsis. Our analysis of the HeLa gene expression profile revealed that several pathways, including cell cycle and DNA repair, exhibit significantly different expression patterns from those in normal human tissues. Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins. This study underscores the importance of accounting for the strikingly aberrant characteristics of HeLa cells when designing and interpreting experiments, and has implications for the use of HeLa as a model of human biology. PMID:23550136

Defining the nociceptor transcriptome

PubMed Central

Thakur, Matthew; Crow, Megan; Richards, Natalie; Davey, Gareth I. J.; Levine, Emma; Kelleher, Jayne H.; Agley, Chibeza C.; Denk, Franziska; Harridge, Stephen D. R.; McMahon, Stephen B.

2014-01-01

Unbiased “omics” techniques, such as next generation RNA-sequencing, can provide entirely novel insights into biological systems. However, cellular heterogeneity presents a significant barrier to analysis and interpretation of these datasets. The neurons of the dorsal root ganglia (DRG) are an important model for studies of neuronal injury, regeneration and pain. The majority of investigators utilize a dissociated preparation of whole ganglia when studying cellular and molecular function. We demonstrate that the standard methods for producing these preparations gives a 10%-neuronal mixture of cells, with the remainder of cells constituting satellite glia and other non-neuronal cell types. Using a novel application of magnetic purification, we consistently obtain over 95% pure, viable neurons from adult tissue, significantly enriched for small diameter nociceptors expressing the voltage gated ion channel Nav1.8. Using genome-wide RNA-sequencing we compare the currently used (10% neuronal) and pure (95% nociceptor) preparations and find 920 genes enriched. This gives an unprecedented insight into the molecular composition of small nociceptive neurons in the DRG, potentially altering the interpretation of previous studies performed at the tissue level, and indicating a number of novel markers of this widely-studied population of cells. We anticipate that the ease of use, affordability and speed of this technique will see it become widely adopted, delivering a greatly improved capacity to study the roles of nociceptors in health and disease. PMID:25426020

VMS-ROT: A New Module of the Virtual Multifrequency Spectrometer for Simulation, Interpretation, and Fitting of Rotational Spectra

PubMed Central

2017-01-01

The Virtual Multifrequency Spectrometer (VMS) is a tool that aims at integrating a wide range of computational and experimental spectroscopic techniques with the final goal of disclosing the static and dynamic physical–chemical properties “hidden” in molecular spectra. VMS is composed of two parts, namely, VMS-Comp, which provides access to the latest developments in the field of computational spectroscopy, and VMS-Draw, which provides a powerful graphical user interface (GUI) for an intuitive interpretation of theoretical outcomes and a direct comparison to experiment. In the present work, we introduce VMS-ROT, a new module of VMS that has been specifically designed to deal with rotational spectroscopy. This module offers an integrated environment for the analysis of rotational spectra: from the assignment of spectral transitions to the refinement of spectroscopic parameters and the simulation of the spectrum. While bridging theoretical and experimental rotational spectroscopy, VMS-ROT is strongly integrated with quantum-chemical calculations, and it is composed of four independent, yet interacting units: (1) the computational engine for the calculation of the spectroscopic parameters that are employed as a starting point for guiding experiments and for the spectral interpretation, (2) the fitting-prediction engine for the refinement of the molecular parameters on the basis of the assigned transitions and the prediction of the rotational spectrum of the target molecule, (3) the GUI module that offers a powerful set of tools for a vis-à-vis comparison between experimental and simulated spectra, and (4) the new assignment tool for the assignment of experimental transitions in terms of quantum numbers upon comparison with the simulated ones. The implementation and the main features of VMS-ROT are presented, and the software is validated by means of selected test cases ranging from isolated molecules of different sizes to molecular complexes. VMS-ROT therefore offers an integrated environment for the analysis of the rotational spectra, with the innovative perspective of an intimate connection to quantum-chemical calculations that can be exploited at different levels of refinement, as an invaluable support and complement for experimental studies. PMID:28742339

Ab initio Study on Ionization Energies of 3-Amino-1-propanol

NASA Astrophysics Data System (ADS)

Wang, Ke-dong; Jia, Ying-bin; Lai, Zhen-jiang; Liu, Yu-fang

2011-06-01

Fourteen conformers of 3-amino-1-propanol as the minima on the potential energy surface are examined at the MP2/6-311++G** level. Their relative energies calculated at B3LYP, MP3 and MP4 levels of theory indicated that two most stable conformers display the intramolecular OH···N hydrogen bonds. The vertical ionization energies of these conformers calculated with ab initio electron propagator theory in the P3/aug-cc-pVTZ approximation are in agreement with experimental data from photoelectron spectroscopy. Natural bond orbital analyses were used to explain the differences of IEs of the highest occupied molecular ortibal of conformers. Combined with statistical mechanics principles, conformational distributions at various temperatures are obtained and the temperature dependence of photoelectron spectra is interpreted.

Phylogeography above the species level for perennial species in a composite genus

PubMed Central

Tremetsberger, Karin; Ortiz, María Ángeles; Terrab, Anass; Balao, Francisco; Casimiro-Soriguer, Ramón; Talavera, María; Talavera, Salvador

2016-01-01

In phylogeography, DNA sequence and fingerprint data at the population level are used to infer evolutionary histories of species. Phylogeography above the species level is concerned with the genealogical aspects of divergent lineages. Here, we present a phylogeographic study to examine the evolutionary history of a western Mediterranean composite, focusing on the perennial species of Helminthotheca (Asteraceae, Cichorieae). We used molecular markers (amplified fragment length polymorphism (AFLP), internal transcribed spacer and plastid DNA sequences) to infer relationships among populations throughout the distributional range of the group. Interpretation is aided by biogeographic and molecular clock analyses. Four coherent entities are revealed by Bayesian mixture clustering of AFLP data, which correspond to taxa previously recognized at the rank of subspecies. The origin of the group was in western North Africa, from where it expanded across the Strait of Gibraltar to the Iberian Peninsula and across the Strait of Sicily to Sicily. Pleistocene lineage divergence is inferred within western North Africa as well as within the western Iberian region. The existence of the four entities as discrete evolutionary lineages suggests that they should be elevated to the rank of species, yielding H. aculeata, H. comosa, H. maroccana and H. spinosa, whereby the latter two necessitate new combinations. PMID:26644340

Quantum biology at the cellular level--elements of the research program.

PubMed

Bordonaro, Michael; Ogryzko, Vasily

2013-04-01

Quantum biology is emerging as a new field at the intersection between fundamental physics and biology, promising novel insights into the nature and origin of biological order. We discuss several elements of QBCL (quantum biology at cellular level) - a research program designed to extend the reach of quantum concepts to higher than molecular levels of biological organization. We propose a new general way to address the issue of environmentally induced decoherence and macroscopic superpositions in biological systems, emphasizing the 'basis-dependent' nature of these concepts. We introduce the notion of 'formal superposition' and distinguish it from that of Schroedinger's cat (i.e., a superposition of macroscopically distinct states). Whereas the latter notion presents a genuine foundational problem, the former one contradicts neither common sense nor observation, and may be used to describe cellular 'decision-making' and adaptation. We stress that the interpretation of the notion of 'formal superposition' should involve non-classical correlations between molecular events in a cell. Further, we describe how better understanding of the physics of Life can shed new light on the mechanism driving evolutionary adaptation (viz., 'Basis-Dependent Selection', BDS). Experimental tests of BDS and the potential role of synthetic biology in closing the 'evolvability mechanism' loophole are also discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Low-level laser therapy on MCF-7 cells: a micro-Fourier transform infrared spectroscopy study

NASA Astrophysics Data System (ADS)

Magrini, Taciana D.; dos Santos, Nathalia Villa; Milazzotto, Marcella Pecora; Cerchiaro, Giselle; da Silva Martinho, Herculano

2012-10-01

Low-level laser therapy (LLLT) is an emerging therapeutic approach for several clinical conditions. The clinical effects induced by LLLT presumably scale from photobiostimulation/photobioinhibition at the cellular level to the molecular level. The detailed mechanism underlying this effect remains unknown. This study quantifies some relevant aspects of LLLT related to molecular and cellular variations. Malignant breast cells (MCF-7) were exposed to spatially filtered light from a He-Ne laser (633 nm) with fluences of 5, 28.8, and 1000 mJ/cm2. The cell viability was evaluated by optical microscopy using the Trypan Blue viability test. The micro-Fourier transform infrared technique was employed to obtain the vibrational spectra of each experimental group (control and irradiated) and identify the relevant biochemical alterations that occurred due to the process. It was observed that the red light influenced the RNA, phosphate, and serine/threonine/tyrosine bands. We found that light can influence cell metabolism depending on the laser fluence. For 5 mJ/cm2, MCF-7 cells suffer bioinhibition with decreased metabolic rates. In contrast, for the 1 J/cm2 laser fluence, cells present biostimulation accompanied by a metabolic rate elevation. Surprisingly, at the intermediate fluence, 28.8 mJ/cm2, the metabolic rate is increased despite the absence of proliferative results. The data were interpreted within the retrograde signaling pathway mechanism activated with light irradiation.

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

PubMed Central

2013-01-01

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology. PMID:24090398

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.

PubMed

Canonica, Giorgio Walter; Ansotegui, Ignacio J; Pawankar, Ruby; Schmid-Grendelmeier, Peter; van Hage, Marianne; Baena-Cagnani, Carlos E; Melioli, Giovanni; Nunes, Carlos; Passalacqua, Giovanni; Rosenwasser, Lanny; Sampson, Hugh; Sastre, Joaquin; Bousquet, Jean; Zuberbier, Torsten

2013-10-03

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.

Energy-level alignment at organic heterointerfaces

PubMed Central

Oehzelt, Martin; Akaike, Kouki; Koch, Norbert; Heimel, Georg

2015-01-01

Today’s champion organic (opto-)electronic devices comprise an ever-increasing number of different organic-semiconductor layers. The functionality of these complex heterostructures largely derives from the relative alignment of the frontier molecular-orbital energies in each layer with respect to those in all others. Despite the technological relevance of the energy-level alignment at organic heterointerfaces, and despite continued scientific interest, a reliable model that can quantitatively predict the full range of phenomena observed at such interfaces is notably absent. We identify the limitations of previous attempts to formulate such a model and highlight inconsistencies in the interpretation of the experimental data they were based on. We then develop a theoretical framework, which we demonstrate to accurately reproduce experiment. Applying this theory, a comprehensive overview of all possible energy-level alignment scenarios that can be encountered at organic heterojunctions is finally given. These results will help focus future efforts on developing functional organic interfaces for superior device performance. PMID:26702447

Stacking fault energies and slip in nanocrystalline metals.

PubMed

Van Swygenhoven, H; Derlet, P M; Frøseth, A G

2004-06-01

The search for deformation mechanisms in nanocrystalline metals has profited from the use of molecular dynamics calculations. These simulations have revealed two possible mechanisms; grain boundary accommodation, and intragranular slip involving dislocation emission and absorption at grain boundaries. But the precise nature of the slip mechanism is the subject of considerable debate, and the limitations of the simulation technique need to be taken into consideration. Here we show, using molecular dynamics simulations, that the nature of slip in nanocrystalline metals cannot be described in terms of the absolute value of the stacking fault energy-a correct interpretation requires the generalized stacking fault energy curve, involving both stable and unstable stacking fault energies. The molecular dynamics technique does not at present allow for the determination of rate-limiting processes, so the use of our calculations in the interpretation of experiments has to be undertaken with care.

Molecular assays in detecting EGFR gene aberrations: an updated HER2-dependent algorithm for interpreting gene signals; a short technical report.

PubMed

Tsiambas, Evangelos; Ragos, Vasileios; Lefas, Alicia Y; Georgiannos, Stavros N; Rigopoulos, Dimitrios N; Georgakopoulos, Georgios; Stamatelopoulos, Athanasios; Grapsa, Dimitra; Syrigos, Konstantinos

2016-01-01

Purpose: Among oncogenes that have already been identified and cloned, Epidermal Growth Factor Receptor (EGFR) remains one of the most significant. Understanding its deregulation mechanisms improves critically patients' selection for personalized therapies based on modern molecular biology and oncology guidelines. Anti-EGFR targeted therapeutic strategies have been developed based on specific genetic profiles and applied in subgroups of patients suffering by solid cancers of different histogenetic origin. Detection of specific EGFR somatic mutations leads to tyrosine kinase inhibitors (TKIs) application in subsets of them. Concerning EGFR gene numerical imbalances, identification of pure gene amplification is critical for targeting the molecule via monoclonal antibodies (mAbs). In the current technical paper we demonstrate the main molecular methods applied in EGFR analyses focused also on new data in interpreting numerical imbalances based on ASCO/ACAP guidelines for HER2 in situ hybridization (ISH) clarifications.

Theoretical Foundation for Electric-Dipole-Allowed Chiral-Specific Fluorescence Optical Rotary Dispersion (F-ORD) from Interfacial Assemblies.

PubMed

Deng, Fengyuan; Ulcickas, James R W; Simpson, Garth J

2016-11-03

Fluorescence optical rotary dispersion (F-ORD) is proposed as a novel chiral-specific and interface-specific spectroscopic method. F-ORD measurements of uniaxial assemblies are predicted to be fully electric-dipole-allowed, with corresponding increases in sensitivity to chirality relative to chiral-specific measurements in isotropic assemblies that are commonly interpreted through coupling between electric and magnetic dynamic dipoles. Observations of strong chiral sensitivity in prior single-molecule fluorescence measurements of chiral interfacial molecules are in excellent qualitative agreement with the predictions of the F-ORD mechanism and challenging to otherwise explain. F-ORD may provide methods to suppress background fluorescence in studies of biological interfaces, as the detected signal requires both polar local order and interfacial chirality. In addition, the molecular-level descriptions of the mechanisms underpinning F-ORD may also potentially apply to aid in interpreting chiral-specific Raman and surface-enhanced Raman spectroscopy measurements of uniaxially oriented assemblies, opening up opportunities for chiral-specific and interface-specific vibrational spectroscopy.

Carbon Nanomembranes

NASA Astrophysics Data System (ADS)

Angelova, Polina; Gölzhäuser, Armin

2017-03-01

This chapter describes the formation and properties of one nanometer thick carbon nanomembranes (CNMs), made by electron induced cross-linking of aromatic self-assembled monolayers (SAMs). The cross-linked SAMs are robust enough to be released from the surface and placed on solid support or over holes as free-standing membranes. Annealing at 1000K transforms CNMs into graphene accompanied by a change of mechanical stiffness and electrical resistance. The developed fabrication approach is scalable and provides molecular level control over thickness and homogeneity of the produced CNMs. The mechanisms of electron-induced cross-linking process are discussed in details. A variety of polyaromatic thiols: oligophenyls as well as small and extended condensed polycyclic hydrocarbons have been successfully employed, demonstrating that the structural and functional properties of the resulting nanomembranes are strongly determined by the structure of molecular monolayers. The mechanical properties of CNMs (Young's modulus, tensile strength and prestress) are characterized by bulge testing. The interpretation of the bulge test data relates the Young's modulus to the properties of single molecules and to the structure of the pristine SAMs. The gas transport through the CNM is measured onto polydimethylsiloxane (PDMS) - thin film composite membrane. The established relationship of permeance and molecular size determines the molecular sieving mechanism of permeation through this ultrathin sheet.

Mapping biological process relationships and disease perturbations within a pathway network.

PubMed

Stoney, Ruth; Robertson, David L; Nenadic, Goran; Schwartz, Jean-Marc

2018-01-01

Molecular interaction networks are routinely used to map the organization of cellular function. Edges represent interactions between genes, proteins, or metabolites. However, in living cells, molecular interactions are dynamic, necessitating context-dependent models. Contextual information can be integrated into molecular interaction networks through the inclusion of additional molecular data, but there are concerns about completeness and relevance of this data. We developed an approach for representing the organization of human cellular processes using pathways as the nodes in a network. Pathways represent spatial and temporal sets of context-dependent interactions, generating a high-level network when linked together, which incorporates contextual information without the need for molecular interaction data. Analysis of the pathway network revealed linked communities representing functional relationships, comparable to those found in molecular networks, including metabolism, signaling, immunity, and the cell cycle. We mapped a range of diseases onto this network and find that pathways associated with diseases tend to be functionally connected, highlighting the perturbed functions that result in disease phenotypes. We demonstrated that disease pathways cluster within the network. We then examined the distribution of cancer pathways and showed that cancer pathways tend to localize within the signaling, DNA processes and immune modules, although some cancer-associated nodes are found in other network regions. Altogether, we generated a high-confidence functional network, which avoids some of the shortcomings faced by conventional molecular models. Our representation provides an intuitive functional interpretation of cellular organization, which relies only on high-quality pathway and Gene Ontology data. The network is available at https://data.mendeley.com/datasets/3pbwkxjxg9/1.

Molecular Diagnostics of Fusion and Laboratory Plasmas

NASA Astrophysics Data System (ADS)

Fantz, U.

2005-05-01

The presence of molecules in the cold scrape-off layer of fusion experiments and industrial plasmas requires an understanding of the molecular dynamics in these low temperature plasmas. Suitable diagnostic methods can provide an insight in molecular processes in the plasma volume as well as for plasma surface interactions. A very simple but powerful technique is the molecular emission spectroscopy. Spectra are obtained easily, whereas interpretation might be very complex and relies on the availability of atomic and molecular data. Examples are given for hydrogen plasmas and plasmas with hydrocarbons which both are of importance in industrial applications as well as in fusion experiments.

Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.

PubMed

McGuire, Mary F; Sriram Iyengar, M; Mercer, David W

2012-04-01

Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction mechanisms may be most effective within a certain time period and for a specific functional relationship. Copyright © 2011 Elsevier Inc. All rights reserved.

Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma

PubMed Central

McGuire, Mary F.; Iyengar, M. Sriram; Mercer, David W.

2012-01-01

Motivation Although trauma is the leading cause of death for those below 45 years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. Results In the node/molecular analysis of the first 24 hours from trauma, PSA uncovered 7 molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which 3 molecules had not been previously associated with any shock / trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships – activation, expression, inhibition, and transcription – and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction mechanisms may be most effective within a certain time period and for a specific functional relationship. PMID:22200681

Rotational Energy as Mass in H3 + and Lower Limits on the Atomic Masses of D and 3He

NASA Astrophysics Data System (ADS)

Smith, J. A.; Hamzeloui, S.; Fink, D. J.; Myers, E. G.

2018-04-01

We have made precise measurements of the cyclotron frequency ratios H3 +/HD+ and H3 +/ 3He+ and observe that different H3+ ions result in different cyclotron frequency ratios. We interpret these differences as due to the molecular rotational energy of H3 + changing its inertial mass. We also confirm that certain high J , K rotational levels of H3+ have mean lifetimes exceeding several weeks. From measurements with the lightest H3+ ion we obtain lower limits on the atomic masses of deuterium and helium-3 with respect to the proton.

Advances in Proteomics Data Analysis and Display Using an Accurate Mass and Time Tag Approach

PubMed Central

Zimmer, Jennifer S.D.; Monroe, Matthew E.; Qian, Wei-Jun; Smith, Richard D.

2007-01-01

Proteomics has recently demonstrated utility in understanding cellular processes on the molecular level as a component of systems biology approaches and for identifying potential biomarkers of various disease states. The large amount of data generated by utilizing high efficiency (e.g., chromatographic) separations coupled to high mass accuracy mass spectrometry for high-throughput proteomics analyses presents challenges related to data processing, analysis, and display. This review focuses on recent advances in nanoLC-FTICR-MS-based proteomics approaches and the accompanying data processing tools that have been developed to display and interpret the large volumes of data being produced. PMID:16429408

The Art of Interpreting Epigenetic Activity | Center for Cancer Research

Cancer.gov

Even though all the cells of the human body share a common genomic blueprint, epigenetic activity such as DNA methylation, introduces molecular diversity that results in functionally and biologically different cellular constituents. In cancers, this ability of epigenetic activity to introduce molecular diversity is emerging as a powerful classifier of biological aggressiveness.

The Development of Students' Mental Models of Chemical Substances and Processes at the Molecular Level

NASA Astrophysics Data System (ADS)

Dalton, Rebecca Marie

The development of student's mental models of chemical substances and processes at the molecular level was studied in a three-phase project. Animations produced in the VisChem project were used as an integral part of the chemistry instruction to help students develop their mental models. Phase one of the project involved examining the effectiveness of using animations to help first-year university chemistry students develop useful mental models of chemical phenomena. Phase two explored factors affecting the development of student's mental models, analysing results in terms of a proposed model of the perceptual processes involved in interpreting an animation. Phase three involved four case studies that served to confirm and elaborate on the effects of prior knowledge and disembedding ability on student's mental model development, and support the influence of study style on learning outcomes. Recommendations for use of the VisChem animations, based on the above findings, include: considering the prior knowledge of students; focusing attention on relevant features; encouraging a deep approach to learning; using animation to teach visual concepts; presenting ideas visually, verbally and conceptually; establishing 'animation literacy'; minimising cognitive load; using animation as feedback; using student drawings; repeating animations; and discussing 'scientific modelling'.

Hyperfine excitation of C2H and C2D by para-H2

NASA Astrophysics Data System (ADS)

Dumouchel, Fabien; Lique, François; Spielfiedel, Annie; Feautrier, Nicole

2017-10-01

The [C2H]/[C2D] abundance ratio is a useful tool to explore the physical and chemical conditions of cold molecular clouds. Hence, an accurate determination of both the C2H and C2D abundances is of fundamental interest. Due to the low density of the interstellar medium, the population of the energy levels of the molecules is not at local thermodynamical equilibrium. Thus, the accurate modelling of the emission spectra requires the calculation of collisional rate coefficients with the most abundant interstellar species. Hence, we provide rate coefficients for the hyperfine excitation of C2H and C2D by para-H2(j=0), the most abundant collisional partner in cold molecular clouds. State-to-state rate coefficients between the lowest levels were computed for temperatures ranging from 5 to 80 K. For both isotopologues, the Δj = ΔF propensity rule is observed. The comparison between C2H and C2D rate coefficients shows that differences by up to a factor of two exist, mainly for Δj = ΔN = 1 transitions. The new rate coefficients will significantly help in the interpretation of recent observed spectra.

The generation of meaningful information in molecular systems.

PubMed

Wills, Peter R

2016-03-13

The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it. © 2016 The Author(s).

Presence of global and local α-relaxations in an alkyl phosphate glass former

NASA Astrophysics Data System (ADS)

Wu, Tao; Jin, Xiao; Saini, Manoj K.; Liu, Ying Dan; Ngai, K. L.; Wang, Li-Min

2017-10-01

The dynamics of a molecular glass former, tributyl phosphate (TBP), with an alkyl phosphate structure (three alkyl branches emanating from a polar core of PO4) is studied in the supercooled regime by dielectric and thermal (or enthalpic) relaxations. The dielectric fragility index md and the stretching exponent βd of the Kohlrausch-Williams-Watts correlation function are determined. Analyses of the enthalpic relaxation data by the Tool-Narayanaswamy-Moynihan-Hodge formalism yield the enthalpic fragility index mH and stretching exponent βH. The large difference between the dielectric md and the enthalpic mH, as well as between βd and βH, is a remarkable finding. The differences are interpreted by the formation of molecular self-assemblies. The interpretation is supported by the quite comparable fragility determined by viscosity and the enthalpic relaxation. The Kirkwood factor calculated at low temperatures is also consistent with the interpretation. The results suggest that the enthalpic relaxation involving the motions of all parts of TBP is global, while the dielectric relaxation detects the local rotation, which might originate from the rotation of the dipole moment of the core. The presence of two structural α-relaxations, one global and one local, with a large difference in dynamics is revealed for the first time in a molecular glass former.

Developments in the CCP4 molecular-graphics project.

PubMed

Potterton, Liz; McNicholas, Stuart; Krissinel, Eugene; Gruber, Jan; Cowtan, Kevin; Emsley, Paul; Murshudov, Garib N; Cohen, Serge; Perrakis, Anastassis; Noble, Martin

2004-12-01

Progress towards structure determination that is both high-throughput and high-value is dependent on the development of integrated and automatic tools for electron-density map interpretation and for the analysis of the resulting atomic models. Advances in map-interpretation algorithms are extending the resolution regime in which fully automatic tools can work reliably, but at present human intervention is required to interpret poor regions of macromolecular electron density, particularly where crystallographic data is only available to modest resolution [for example, I/sigma(I) < 2.0 for minimum resolution 2.5 A]. In such cases, a set of manual and semi-manual model-building molecular-graphics tools is needed. At the same time, converting the knowledge encapsulated in a molecular structure into understanding is dependent upon visualization tools, which must be able to communicate that understanding to others by means of both static and dynamic representations. CCP4 mg is a program designed to meet these needs in a way that is closely integrated with the ongoing development of CCP4 as a program suite suitable for both low- and high-intervention computational structural biology. As well as providing a carefully designed user interface to advanced algorithms of model building and analysis, CCP4 mg is intended to present a graphical toolkit to developers of novel algorithms in these fields.

The Importance of Quality in Ventilation-Perfusion Imaging.

PubMed

Mann, April; DiDea, Mario; Fournier, France; Tempesta, Daniel; Williams, Jessica; LaFrance, Norman

2018-06-01

As the health care environment continues to change and morph into a system focusing on increased quality and evidence-based outcomes, nuclear medicine technologists must be reminded that they play a critical role in achieving high-quality, interpretable images used to drive patient care, treatment, and best possible outcomes. A survey performed by the Quality Committee of the Society of Nuclear Medicine and Molecular Imaging Technologist Section demonstrated that a clear knowledge gap exists among technologists regarding their understanding of quality, how it is measured, and how it should be achieved by all practicing technologists regardless of role and education level. Understanding of these areas within health care, in conjunction with the growing emphasis on evidence-based outcomes, quality measures, and patient satisfaction, will ultimately elevate the role of nuclear medicine technologists today and into the future. The nuclear medicine role now requires technologists to demonstrate patient assessment skills, practice safety procedures with regard to staff and patients, provide patient education and instruction, and provide physicians with information to assist with the interpretation and outcome of the study. In addition, the technologist must be able to evaluate images by performing technical analysis, knowing the demonstrated anatomy and pathophysiology, and assessing overall quality. Technologists must also be able to triage and understand the disease processes being evaluated and how nuclear medicine diagnostic studies may drive care and treatment. Therefore, it is imperative that nuclear medicine technologists understand their role in the achievement of a high-quality, interpretable study by applying quality principles and understanding and using imaging techniques beyond just basic protocols for every type of disease or system being imaged. This article focuses on quality considerations related to ventilation-perfusion imaging. It provides insight on appropriate imaging techniques and protocols, true imaging variants and tracer distributions versus artifacts that may result in a lower-quality or misinterpreted study, and the use of SPECT and SPECT/CT as an alternative providing a high-quality, interpretable study with better diagnostic accuracy and fewer nondiagnostic procedures than historical planar imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Multi-color electron microscopy by element-guided identification of cells, organelles and molecules.

PubMed

Scotuzzi, Marijke; Kuipers, Jeroen; Wensveen, Dasha I; de Boer, Pascal; Hagen, Kees C W; Hoogenboom, Jacob P; Giepmans, Ben N G

2017-04-07

Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale 'color-EM' as a promising tool to unravel molecular (de)regulation in biomedicine.

Multi-color electron microscopy by element-guided identification of cells, organelles and molecules

PubMed Central

Scotuzzi, Marijke; Kuipers, Jeroen; Wensveen, Dasha I.; de Boer, Pascal; Hagen, Kees (C.) W.; Hoogenboom, Jacob P.; Giepmans, Ben N. G.

2017-01-01

Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale ‘color-EM’ as a promising tool to unravel molecular (de)regulation in biomedicine. PMID:28387351

Tradeoffs in the design of a system for high level language interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osorio, F.C.C.; Patt, Y.N.

The problem of designing a system for high-level language interpretation (HLLI) is considered. First, a model of the design process is presented where several styles of design, e.g. turing machine interpretation, CISC architecture interpretation and RISC architecture interpretation are treated uniformly. Second, the most significant characteristics of HLLI are analysed in the context of different design styles, and some guidelines are presented on how to identify the most suitable design style for a given high-level language problem. 12 references.

[Relevance of big data for molecular diagnostics].

PubMed

Bonin-Andresen, M; Smiljanovic, B; Stuhlmüller, B; Sörensen, T; Grützkau, A; Häupl, T

2018-04-01

Big data analysis raises the expectation that computerized algorithms may extract new knowledge from otherwise unmanageable vast data sets. What are the algorithms behind the big data discussion? In principle, high throughput technologies in molecular research already introduced big data and the development and application of analysis tools into the field of rheumatology some 15 years ago. This includes especially omics technologies, such as genomics, transcriptomics and cytomics. Some basic methods of data analysis are provided along with the technology, however, functional analysis and interpretation requires adaptation of existing or development of new software tools. For these steps, structuring and evaluating according to the biological context is extremely important and not only a mathematical problem. This aspect has to be considered much more for molecular big data than for those analyzed in health economy or epidemiology. Molecular data are structured in a first order determined by the applied technology and present quantitative characteristics that follow the principles of their biological nature. These biological dependencies have to be integrated into software solutions, which may require networks of molecular big data of the same or even different technologies in order to achieve cross-technology confirmation. More and more extensive recording of molecular processes also in individual patients are generating personal big data and require new strategies for management in order to develop data-driven individualized interpretation concepts. With this perspective in mind, translation of information derived from molecular big data will also require new specifications for education and professional competence.

Antioxidant behavior of mearnsetin and myricetin flavonoid compounds — A DFT study

NASA Astrophysics Data System (ADS)

Sadasivam, K.; Kumaresan, R.

2011-06-01

The molecular characteristics of two naturally occurring flavonoid compounds mearnsetin and myricetin have been computed using density functional theory (DFT) approach with B3LYP/6-311G(d,p) level of theory. The computation and analysis of bond dissociation enthalpy magnitudes for all the OH sites for both the compounds clearly denotes the contribution of the B-ring for the antioxidant activity. The analysis has also indicated the higher values of BDE on the C5-OH radical species in both the compounds. The computed vibrational frequency analysis indicates the absence of imaginary frequency in the neutral as well as radical species of both the flavonoid compounds. The ionisation potential (IP) analysis was found to be within the range of the IP of synthetic food additives. In addition, various molecular descriptors such as electron affinity, hardness, softness, electronegativity, electrophilic index have also been calculated and the validity of Koopman's theorem is verified. The plot of frontier molecular orbital and spin density distribution analysis for neutral and the corresponding radical species for both the compounds have been computed and interpreted. The polar nature and their polarizing capacity are well established through the analysis of dipole moment and polarisability magnitudes.

Crankshaft motion in a highly congested bis(triarylmethyl)peroxide.

PubMed

Khuong, Tinh-Alfredo V; Zepeda, Gerardo; Sanrame, Carlos N; Dang, Hung; Bartberger, Michael D; Houk, K N; Garcia-Garibay, Miguel A

2004-11-17

Crankshaft motion has been proposed in the solid state for molecular fragments consisting of three or more rotors linked by single bonds, whereby the two terminal rotors are static and the internal rotors experience circular motion. Bis-[tri-(3,5-di-tert-butyl)phenylmethyl]-peroxide 2 was tested as a model in search of crankshaft motion at the molecular level. In the case of peroxide 2, the bulky trityl groups may be viewed as the external static rotors, while the two peroxide oxygens can undergo the sought after internal rotation. Evidence for this process in the case of peroxide 2 was obtained from conformational dynamics determined by variable-temperature (13)C and (1)H NMR between 190 and 375 K in toluene-d(8). Detailed spectral assignments for the interpretation of two coalescence processes were based on a correlation between NMR spectra obtained in solution at low temperature, in the solid state by (13)C CPMAS NMR, and by GIAO calculations based on a B3LYP/6-31G structure of 2 obtained from its X-ray coordinates as the input. Evidence supporting crankshaft rotation rather than slippage of the trityl groups was obtained from molecular mechanics calculations.

Molecular structure, vibrational spectra, NBO analysis and molecular packing prediction of 3-nitroacetanilide by ab initio HF and density functional theory.

PubMed

Li, Xiao-Hong; Li, Tong-Wei; Ju, Wei-Wei; Yong, Yong-Liang; Zhang, Xian-Zhou

2014-01-24

Quantum chemical calculations of geometries and vibrational wavenumbers of 3-nitroacetanilide (C8H8N2O3) in the ground state were carried out by using ab initio HF and density functional theory (DFT/B3LYP) methods with 6-31+G(*) basis set. The -311++G(**) basis set is also used for B3LYP level. The scaled harmonic vibrational frequencies have been compared with experimental FT-IR spectra. Theoretical vibrational spectra of the title compound were interpreted by means of potential energies distributions (PEDs) using MOLVIB program. The theoretical spectrograms for IR spectra of the title compound have been constructed. The shortening of C-H bond length and the elongation of N-H bond length suggest the existence of weak C-H⋯O and N-H⋯O hydrogen bonds, which is confirmed by the natural bond orbital analysis. In addition, the crystal structure obtained by molecular mechanics belongs to the P2(1) space group, with lattice parameters Z=4, a=14.9989 Å, b=4.0367 Å, c=12.9913 Å, ρ=0.998 g cm(-3). Copyright © 2013 Elsevier B.V. All rights reserved.

Molecular structure, vibrational spectra, NBO analysis and molecular packing prediction of 3-nitroacetanilide by ab initio HF and density functional theory

NASA Astrophysics Data System (ADS)

Li, Xiao-Hong; Li, Tong-Wei; Ju, Wei-Wei; Yong, Yong-Liang; Zhang, Xian-Zhou

2014-01-01

Quantum chemical calculations of geometries and vibrational wavenumbers of 3-nitroacetanilide (C8H8N2O3) in the ground state were carried out by using ab initio HF and density functional theory (DFT/B3LYP) methods with 6-31+G* basis set. The -311++G** basis set is also used for B3LYP level. The scaled harmonic vibrational frequencies have been compared with experimental FT-IR spectra. Theoretical vibrational spectra of the title compound were interpreted by means of potential energies distributions (PEDs) using MOLVIB program. The theoretical spectrograms for IR spectra of the title compound have been constructed. The shortening of Csbnd H bond length and the elongation of Nsbnd H bond length suggest the existence of weak Csbnd H⋯O and Nsbnd H⋯O hydrogen bonds, which is confirmed by the natural bond orbital analysis. In addition, the crystal structure obtained by molecular mechanics belongs to the P21 space group, with lattice parameters Z = 4, a = 14.9989 Å, b = 4.0367 Å, c = 12.9913 Å, ρ = 0.998 g cm-3.

Atomic and molecular supernovae

NASA Technical Reports Server (NTRS)

Liu, Weihong

1997-01-01

Atomic and molecular physics of supernovae is discussed with an emphasis on the importance of detailed treatments of the critical atomic and molecular processes with the best available atomic and molecular data. The observations of molecules in SN 1987A are interpreted through a combination of spectral and chemical modelings, leading to strong constraints on the mixing and nucleosynthesis of the supernova. The non-equilibrium chemistry is used to argue that carbon dust can form in the oxygen-rich clumps where the efficient molecular cooling makes the nucleation of dust grains possible. For Type Ia supernovae, the analyses of their nebular spectra lead to strong constraints on the supernova explosion models.

An Expanded Framework for Biomolecular Visualization in the Classroom: Learning Goals and Competencies

ERIC Educational Resources Information Center

Dries, Daniel R.; Dean, Diane M.; Listenberger, Laura L.; Novak, Walter R. P.; Franzen, Margaret A.; Craig, Paul A.

2017-01-01

A thorough understanding of the molecular biosciences requires the ability to visualize and manipulate molecules in order to interpret results or to generate hypotheses. While many instructors in biochemistry and molecular biology use visual representations, few indicate that they explicitly teach visual literacy. One reason is the need for a list…

Quantitative Detection of Low-Abundance Transcripts at Single-Cell Level in Human Epidermal Keratinocytes by Digital Droplet Reverse Transcription-Polymerase Chain Reaction.

PubMed

Auvré, Frédéric; Coutier, Julien; Martin, Michèle T; Fortunel, Nicolas O

2018-05-08

Genetic and epigenetic characterization of the large cellular diversity observed within tissues is essential to understanding the molecular networks that ensure the regulation of homeostasis, repair, and regeneration, but also pathophysiological processes. Skin is composed of multiple cell lineages and is therefore fully concerned by this complexity. Even within one particular lineage, such as epidermal keratinocytes, different immaturity statuses or differentiation stages are represented, which are still incompletely characterized. Accordingly, there is presently great demand for methods and technologies enabling molecular investigation at single-cell level. Also, most current methods used to analyze gene expression at RNA level, such as RT-qPCR, do not directly provide quantitative data, but rather comparative ratios between two conditions. A second important need in skin biology is thus to determine the number of RNA molecules in a given cell sample. Here, we describe a workflow that we have set up to meet these specific needs, by means of transcript quantification in cellular micro-samples using flow cytometry sorting and reverse transcription-digital droplet polymerase chain reaction. As a proof-of-principle, the workflow was tested for the detection of transcription factor transcripts expressed at low levels in keratinocyte precursor cells. A linear correlation was found between quantification values and keratinocyte input numbers in a low quantity range from 40 cells to 1 cell. Interpretable signals were repeatedly obtained from single-cell samples corresponding to estimated expression levels as low as 10-20 transcript copies per keratinocyte or less. The present workflow may have broad applications for the detection and quantification of low-abundance nucleic acid species in single cells, opening up perspectives for the study of cell-to-cell genetic and molecular heterogeneity. Interestingly, the process described here does not require internal references such as house-keeping gene expression, as it is initiated with defined cell numbers, precisely sorted by flow cytometry.

Exploring an optimal wavelet-based filter for cryo-ET imaging.

PubMed

Huang, Xinrui; Li, Sha; Gao, Song

2018-02-07

Cryo-electron tomography (cryo-ET) is one of the most advanced technologies for the in situ visualization of molecular machines by producing three-dimensional (3D) biological structures. However, cryo-ET imaging has two serious disadvantages-low dose and low image contrast-which result in high-resolution information being obscured by noise and image quality being degraded, and this causes errors in biological interpretation. The purpose of this research is to explore an optimal wavelet denoising technique to reduce noise in cryo-ET images. We perform tests using simulation data and design a filter using the optimum selected wavelet parameters (three-level decomposition, level-1 zeroed out, subband-dependent threshold, a soft-thresholding and spline-based discrete dyadic wavelet transform (DDWT)), which we call a modified wavelet shrinkage filter; this filter is suitable for noisy cryo-ET data. When testing using real cryo-ET experiment data, higher quality images and more accurate measures of a biological structure can be obtained with the modified wavelet shrinkage filter processing compared with conventional processing. Because the proposed method provides an inherent advantage when dealing with cryo-ET images, it can therefore extend the current state-of-the-art technology in assisting all aspects of cryo-ET studies: visualization, reconstruction, structural analysis, and interpretation.

Assessing the Level of Performance of Sign Language Interpreters from Impaired Hearing Students' Perspectives at Public and Private Jordanian Universities

ERIC Educational Resources Information Center

Shanikat, Feryal Abdel-Hadi

2014-01-01

This study aimed at assessing the level of performance of sign language interpreters in both public and private Jordanian universities, as well as to recognize the effect of the study variables specifically gender and qualifications for acoustically disabled and interpreter, and the experience of the interpreter on the level of the performance…

Epistasis increases the rate of conditionally neutral substitution in an adapting population.

PubMed

Draghi, Jeremy A; Parsons, Todd L; Plotkin, Joshua B

2011-04-01

Kimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations--i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations--substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations.

Epistasis Increases the Rate of Conditionally Neutral Substitution in an Adapting Population

PubMed Central

Draghi, Jeremy A.; Parsons, Todd L.; Plotkin, Joshua B.

2011-01-01

Kimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations—i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations—substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations. PMID:21288876

Hydrophobic Hydration of Stimulus-Responsive Polyproteins Measured by Single Molecule Force Spectroscopy

NASA Astrophysics Data System (ADS)

Zauscher, Stefan

2007-03-01

We present a new procedure to reduce and analyze force-extension data obtained by single molecule force spectroscopy (SMFS). This approach allows, for the first time, to infer effects of solvent quality and minor changes in molecular architecture on molecular-elasticity of individual (bio)macromolecules. Specifically, we show how changes in the effective Kuhn segment length can be used to interpret the hydrophobic hydration behavior of elastin-like polypeptides (ELPs).Our results are intriguing as they suggest that SMFS in combination with our analysis procedure can be used to study the subtleties of polypeptide-water interactions on the single molecule level. We also report on the force-induced cis-trans isomerization of prolines, which are repeated every fifth residue in the main chain of ELPs. We present evidence for this mechanism by Monte Carlo simulations of the force-extension curves using an elastically coupled two-state system. Our results suggest that SMFS could be used to assay proline cis-trans isomerization in proteins and may thus have significant potential diagnostic utility.

[Microarray CGH: principle and use for constitutional disorders].

PubMed

Sanlaville, D; Lapierre, J M; Coquin, A; Turleau, C; Vermeesch, J; Colleaux, L; Borck, G; Vekemans, M; Aurias, A; Romana, S P

2005-10-01

Chips technology has allowed to miniaturize process making possible to realize in one step and using the same device a lot of chemical reactions. The application of this technology to molecular cytogenetics resulted in the development of comparative genomic hybridization (CGH) on microarrays technique. Using this technique it is possible to detect very small genetic imbalances anywhere in the genome. Its usefulness has been well documented in cancer and more recently in constitutional disorders. In particular it has been used to detect interstitial and subtelomeric submicroscopic imbalances, to characterize their size at the molecular level or to define the breakpoints of translocation. The challenge today is to transfer this technology in laboratory medicine. Nevertheless this technology remains expensive and the existence of numerous sequence polymorphisms makes its interpretation difficult. Finally its is unlikely that it will make karyotyping obsolete as it does not allow to detect balanced rearrangements which after meiotic segregation might result in genome imbalance in the progeny.

Entropy of Leukemia on Multidimensional Morphological and Molecular Landscapes

NASA Astrophysics Data System (ADS)

Vilar, Jose M. G.

2014-04-01

Leukemia epitomizes the class of highly complex diseases that new technologies aim to tackle by using large sets of single-cell-level information. Achieving such a goal depends critically not only on experimental techniques but also on approaches to interpret the data. A most pressing issue is to identify the salient quantitative features of the disease from the resulting massive amounts of information. Here, I show that the entropies of cell-population distributions on specific multidimensional molecular and morphological landscapes provide a set of measures for the precise characterization of normal and pathological states, such as those corresponding to healthy individuals and acute myeloid leukemia (AML) patients. I provide a systematic procedure to identify the specific landscapes and illustrate how, applied to cell samples from peripheral blood and bone marrow aspirates, this characterization accurately diagnoses AML from just flow cytometry data. The methodology can generally be applied to other types of cell populations and establishes a straightforward link between the traditional statistical thermodynamics methodology and biomedical applications.

Tailoring the properties of acetate-based ionic liquids using the tricyanomethanide anion.

PubMed

Lepre, L F; Szala-Bilnik, J; Padua, A A H; Traïkia, M; Ando, R A; Costa Gomes, M F

2016-08-17

The equilibrium and transport properties of mixtures of two ionic liquids - [C4C1Im][OAc] and [C4C1Im][C(CN)3] - were determined and interpreted at the molecular level using vibration spectroscopy, NMR and molecular dynamics simulation. The non-ideality of the mixtures [C4C1Im][OAc](1-x)[C(CN)3]x was characterized by V(E) = +0.28 cm(3) mol(-1) (293 K, x = 0.65) and H(E) = -2.2 kJ mol(-1) for x = 0.5. These values could be explained by a rearrangement of the hydrogen-bond network of the mixture that favours the interaction of the acetate anion with the imidazolium cation at position C2. The dynamic properties of the mixture are also dramatically influenced by the composition with a decrease of the viscosity and an increase of self-diffusion coefficients of the ions when the amount of tricyanomethanide anion increases in the mixture.

Inquiry-based experiments for large-scale introduction to PCR and restriction enzyme digests.

PubMed

Johanson, Kelly E; Watt, Terry J

2015-01-01

Polymerase chain reaction and restriction endonuclease digest are important techniques that should be included in all Biochemistry and Molecular Biology laboratory curriculums. These techniques are frequently taught at an advanced level, requiring many hours of student and faculty time. Here we present two inquiry-based experiments that are designed for introductory laboratory courses and combine both techniques. In both approaches, students must determine the identity of an unknown DNA sequence, either a gene sequence or a primer sequence, based on a combination of PCR product size and restriction digest pattern. The experimental design is flexible, and can be adapted based on available instructor preparation time and resources, and both approaches can accommodate large numbers of students. We implemented these experiments in our courses with a combined total of 584 students and have an 85% success rate. Overall, students demonstrated an increase in their understanding of the experimental topics, ability to interpret the resulting data, and proficiency in general laboratory skills. © 2015 The International Union of Biochemistry and Molecular Biology.

Enzymatic cybernetics: an unpublished work by Jacques Monod.

PubMed

Gayon, Jean

2015-06-01

In 1959, Jacques Monod wrote a manuscript entitled Cybernétique enzymatique [Enzymatic cybernetics]. Never published, this unpublished manuscript presents a synthesis of how Monod interpreted enzymatic adaptation just before the publication of the famous papers of the 1960s on the operon. In addition, Monod offers an example of a philosophy of biology immersed in scientific investigation. Monod's philosophical thoughts are classified into two categories, methodological and ontological. On the methodological side, Monod explicitly hints at his preferences regarding the scientific method in general: hypothetical-deductive method, and use of theoretical models. He also makes heuristic proposals regarding molecular biology: the need to analyse the phenomena in question at the level of individual cells, and the dual aspect of all biological explanation, functional and evolutionary. Ontological issues deal with the notions of information and genetic determinism, "cellular memory", the irrelevance of the notion of "living matter", and the usefulness of a cybernetic comprehension of molecular biology. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Interaction between perylene-derivated molecules observed by low temperature scanning tunneling microscopy

NASA Astrophysics Data System (ADS)

Vernisse, Loranne; Guillermet, Olivier; Gourdon, André; Coratger, Roland

2018-03-01

Derivative perylene molecules deposited on Ag(111) and on NaCl(001) ultrathin layers have been investigated using low temperature STM and NC-AFM. When the metallic substrate is held at ambient temperature during evaporation, the molecules form characteristic trimers on the Ag(111) surface and interact through their polar groups. Close to the steps, the molecules form linear structures and seems to stand side by side. On the other hand, after deposition on a substrate cooled at liquid helium temperature, single molecules are observed both on metal and on NaCl. On the ultrathin insulator layers, the STM images present characteristic contrasts related to the molecular orbitals which favors the localization of aldehyde groups. In this case, the lateral molecular interactions may induce the formation of small assemblies in which the electronic levels are slightly shifted. A possible interpretation of this phenomenon is to take into account polar interactions and charge transfer between neighboring molecules.

Synthesis, spectroscopic characterization and crystallographic behavior of a biologically relevant novel indole-fused heterocyclic compound - Experimental and theoretical (DFT) studies

NASA Astrophysics Data System (ADS)

Sharma, Sakshi; Brahmachari, Goutam; Banerjee, Bubun; Nurjamal, Khondekar; Kumar, Abhishek; Srivastava, Ambrish Kumar; Misra, Neeraj; Pandey, Sarvesh Kumar; Rajnikant; Gupta, Vivek K.

2016-08-01

The present communication deals with the eco-friendly synthesis, spectral properties and X-ray crystal structure of an indole derivative - Ethyl 2'-amino-3'-cyano-6'-methyl-5-nitro-2-oxospiro [indoline-3,4'-pyran]-5'-carboxylate. The title compound was synthesized in 87% yield. The crystal structure of the molecule is stabilized by intermolecular Nsbnd H … N, Nsbnd H … O and Csbnd H … π interactions. The molecule is organized in the crystal lattice forming sheet like structure. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 09 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-31 + G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) with frontier orbital gap were presented. The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and density of states (DOS). From the optimized geometry of the molecule, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMOs) of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compound.

FT-Raman study of deferoxamine and deferiprone exhibits potent amelioration of structural changes in the liver tissues of mice due to aluminum exposure

NASA Astrophysics Data System (ADS)

Sivakumar, S.; Khatiwada, Chandra Prasad; Sivasubramanian, J.; Raja, B.

2014-01-01

The present study inform the alterations on major biochemical constituents such as lipids, proteins, nucleic acids and glycogen along with phosphodiester linkages, tryptophan bands, tyrosine doublet, disulfide bridge conformations, aliphatic hydrophobic residue, and salt bridges in liver tissues of mice using Fourier transform Raman spectroscopy. In amide I, amide II and amide III, the area value significant decrease due structural alteration in the protein, glycogen and triglycerides levels but chelating agents DFP and DFO upturned it. Morphology changes by aluminium induced alterations and recovery by chelating agents within liver tissues known by histopathological examination. Concentrations of trace elements were found by ICP-OES. FT-Raman study was revealed to be in agreement with biochemical studies and demonstrate that it can successfully specify the molecular alteration in liver tissues. The tyrosyl doublet ratio I899/I831 decreases more in aluminum intoxicated tissues but treatment with DFP and DFO + DFP brings back to nearer control value. This indicates more variation in the hydrogen bonding of the phenolic hydroxyl group due to aluminum poisoning. The decreased Raman intensity ratio (I3220/I3400) observed in the aluminum induced tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the aluminum intoxicated liver tissues. Finally, FT-Raman spectroscopy might be a useful tool for obtained successfully to indicate the molecular level changes.

Deep proteomic profiling of vasopressin-sensitive collecting duct cells. I. Virtual Western blots and molecular weight distributions.

PubMed

Yang, Chin-Rang; Tongyoo, Pumipat; Emamian, Milad; Sandoval, Pablo C; Raghuram, Viswanathan; Knepper, Mark A

2015-12-15

The mouse mpkCCD cell line is a continuous cultured epithelial cell line with characteristics of renal collecting duct principal cells. This line is widely used to study epithelial transport and its regulation. To provide a data resource useful for experimental design and interpretation in studies using mpkCCD cells, we have carried out "deep" proteomic profiling of these cells using three levels of fractionation (differential centrifugation, SDS-PAGE, and HPLC) followed by tandem mass spectrometry to identify and quantify proteins. The analysis of all resulting samples generated 34.6 gigabytes of spectral data. As a result, we identified 6,766 proteins in mpkCCD cells at a high level of stringency. These proteins are expressed over eight orders of magnitude of protein abundance. The data are provided to users as a public data base (https://helixweb.nih.gov/ESBL/Database/mpkFractions/). The mass spectrometry data were mapped back to their gel slices to generate "virtual Western blots" for each protein. For most of the 6,766 proteins, the apparent molecular weight from SDS-PAGE agreed closely with the calculated molecular weight. However, a substantial fraction (>15%) of proteins was found to run aberrantly, with much higher or much lower mobilities than predicted. These proteins were analyzed to identify mechanisms responsible for altered mobility on SDS-PAGE, including high or low isoelectric point, high or low hydrophobicity, physiological cleavage, residence in the lysosome, posttranslational modifications, and expression of alternative isoforms due to alternative exon usage. Additionally, this analysis identified a previously unrecognized isoform of aquaporin-2 with apparent molecular mass <20 kDa. Copyright © 2015 the American Physiological Society.

Deep proteomic profiling of vasopressin-sensitive collecting duct cells. I. Virtual Western blots and molecular weight distributions

PubMed Central

Yang, Chin-Rang; Tongyoo, Pumipat; Emamian, Milad; Sandoval, Pablo C.; Raghuram, Viswanathan

2015-01-01

The mouse mpkCCD cell line is a continuous cultured epithelial cell line with characteristics of renal collecting duct principal cells. This line is widely used to study epithelial transport and its regulation. To provide a data resource useful for experimental design and interpretation in studies using mpkCCD cells, we have carried out “deep” proteomic profiling of these cells using three levels of fractionation (differential centrifugation, SDS-PAGE, and HPLC) followed by tandem mass spectrometry to identify and quantify proteins. The analysis of all resulting samples generated 34.6 gigabytes of spectral data. As a result, we identified 6,766 proteins in mpkCCD cells at a high level of stringency. These proteins are expressed over eight orders of magnitude of protein abundance. The data are provided to users as a public data base (https://helixweb.nih.gov/ESBL/Database/mpkFractions/). The mass spectrometry data were mapped back to their gel slices to generate “virtual Western blots” for each protein. For most of the 6,766 proteins, the apparent molecular weight from SDS-PAGE agreed closely with the calculated molecular weight. However, a substantial fraction (>15%) of proteins was found to run aberrantly, with much higher or much lower mobilities than predicted. These proteins were analyzed to identify mechanisms responsible for altered mobility on SDS-PAGE, including high or low isoelectric point, high or low hydrophobicity, physiological cleavage, residence in the lysosome, posttranslational modifications, and expression of alternative isoforms due to alternative exon usage. Additionally, this analysis identified a previously unrecognized isoform of aquaporin-2 with apparent molecular mass <20 kDa. PMID:26310816

New insight into the IR-spectra/structure relationship in amyloid fibrils: a theoretical study on a prion peptide.

PubMed

Zanetti Polzi, Laura; Amadei, Andrea; Aschi, Massimiliano; Daidone, Isabella

2011-08-03

Molecular-level structural information on amyloid aggregates is of great importance for the understanding of protein-misfolding-related deseases. Nevertheless, this kind of information is experimentally difficult to obtain. In this work, we used molecular dynamics (MD) simulations combined with a mixed quantum mechanics/molecular mechanics theoretical methodology, the perturbed matrix method (PMM), in order to study the amide I' IR spectrum of fibrils formed by a short peptide, the H1 peptide, derived from residues 109 through 122 of the Syrian hamster prion protein. The PMM/MD approach allows isolation of the amide I' signal arising from any desired peptide group of the polypeptide chain and quantification of the effect of the excitonic coupling on the frequency position. The calculated single-residue signals were found to be in good agreement with the experimental site-specific spectra obtained by means of isotope-labeled IR spectroscopy, providing a means for their interpretation at the molecular level. In particular, our results confirm the experimental hypothesis that residues ala117 are aligned in all strands and that the alignment gives rise to a red shift of the corresponding site-specific amide I' mode due to strong excitonic coupling among the ala117 peptide groups. In addition, our data show that a red shift of the amide I' band due to strong excitonic coupling can also occur for amino acids adjacent in sequence to the aligned ones. Thus, a red shift of the signal of a given isotope-labeled amino acid does not necessarily imply that the peptide groups under consideration are aligned in the β-sheet.

The Mathematics of the Brain

DTIC Science & Technology

2009-05-27

should not be interpreted as representing the official policies, either expressed or implied, of the Defence Advanced Research Project Agency or the... neurobiological interpretation of E-states? 36 8.5 The statistical molecular dynamics of E-states 37 8.6 The C++ program EPMM 40 9 Promising...have an intuitive link between E-machines and neural networks. Such a link provides a source of neurobiological heuristic considerations for the design

Low-level laser therapy on MCF-7 cells: a micro-Fourier transform infrared spectroscopy study.

PubMed

Magrini, Taciana D; dos Santos, Nathalia Villa; Milazzotto, Marcella Pecora; Cerchiaro, Giselle; da Silva Martinho, Herculano

2012-10-01

Low-level laser therapy (LLLT) is an emerging therapeutic approach for several clinical conditions. The clinical effects induced by LLLT presumably scale from photobiostimulation/photobioinhibition at the cellular level to the molecular level. The detailed mechanism underlying this effect remains unknown. This study quantifies some relevant aspects of LLLT related to molecular and cellular variations. Malignant breast cells (MCF-7) were exposed to spatially filtered light from a He-Ne laser (633 nm) with fluences of 5, 28.8, and 1000  mJ/cm². The cell viability was evaluated by optical microscopy using the Trypan Blue viability test. The micro-Fourier transform infrared technique was employed to obtain the vibrational spectra of each experimental group (control and irradiated) and identify the relevant biochemical alterations that occurred due to the process. It was observed that the red light influenced the RNA, phosphate, and serine/threonine/tyrosine bands. We found that light can influence cell metabolism depending on the laser fluence. For 5  mJ/cm², MCF-7 cells suffer bioinhibition with decreased metabolic rates. In contrast, for the 1  J/cm² laser fluence, cells present biostimulation accompanied by a metabolic rate elevation. Surprisingly, at the intermediate fluence, 28.8  mJ/cm², the metabolic rate is increased despite the absence of proliferative results. The data were interpreted within the retrograde signaling pathway mechanism activated with light irradiation.

Excited State Chemistry in the Free Stream of the NASA IHF Arc Jet Facility Observed by Emission Spectroscopy

NASA Technical Reports Server (NTRS)

Winter, Michael W.; Prabhu, Dinesh K.

2011-01-01

Spectroscopic measurements of non-equilibrium emission were made in the free stream of the 60 megawatts Interaction Heating Facility at NASA Ames Research Center. In the visible near infrared wavelength region, the most prominent emission was from molecular N2, and in the ultra violet region, the spectra were dominated by emission from molecular NO. The only atomic lines observed were those of copper (an erosion product of the electrodes). The bands of the 1st Positive system of N2 (if B is true then A is true) differed significantly from spectra computed spectra assuming only thermal excitation, suggesting overpopulation of the high vibrational states of the B state of N2. Populations of these high vibrational levels (peaking at v (sub upper) equals 13) of the N2 B state were determined by scaling simulated spectra; calculations were performed for each upper vibrational state separately. The experimental-theoretical procedure was repeated for several radial positions away from the nozzle axis to obtain spatial distributions of the upper state populations; rotational symmetry of the flow was assumed in simulations. The overpopulation of the high vibrational levels has been interpreted as the effect of inverse pre-dissociation of neutral atoms in the N2 A state, which populates the N2 B state through a level crossing process at v (sub upper) is greater than 10.

Radiative transfer in molecular lines

NASA Astrophysics Data System (ADS)

Asensio Ramos, A.; Trujillo Bueno, J.; Cernicharo, J.

2001-07-01

The highly convergent iterative methods developed by Trujillo Bueno and Fabiani Bendicho (1995) for radiative transfer (RT) applications are generalized to spherical symmetry with velocity fields. These RT methods are based on Jacobi, Gauss-Seidel (GS), and SOR iteration and they form the basis of a new NLTE multilevel transfer code for atomic and molecular lines. The benchmark tests carried out so far are presented and discussed. The main aim is to develop a number of powerful RT tools for the theoretical interpretation of molecular spectra.

Sketching the Invisible to Predict the Visible: From Drawing to Modeling in Chemistry.

PubMed

Cooper, Melanie M; Stieff, Mike; DeSutter, Dane

2017-10-01

Sketching as a scientific practice goes beyond the simple act of inscribing diagrams onto paper. Scientists produce a wide range of representations through sketching, as it is tightly coupled to model-based reasoning. Chemists in particular make extensive use of sketches to reason about chemical phenomena and to communicate their ideas. However, the chemical sciences have a unique problem in that chemists deal with the unseen world of the atomic-molecular level. Using sketches, chemists strive to develop causal mechanisms that emerge from the structure and behavior of molecular-level entities, to explain observations of the macroscopic visible world. Interpreting these representations and constructing sketches of molecular-level processes is a crucial component of student learning in the modern chemistry classroom. Sketches also serve as an important component of assessment in the chemistry classroom as student sketches give insight into developing mental models, which allows instructors to observe how students are thinking about a process. In this paper we discuss how sketching can be used to promote such model-based reasoning in chemistry and discuss two case studies of curricular projects, CLUE and The Connected Chemistry Curriculum, that have demonstrated a benefit of this approach. We show how sketching activities can be centrally integrated into classroom norms to promote model-based reasoning both with and without component visualizations. Importantly, each of these projects deploys sketching in support of other types of inquiry activities, such as making predictions or depicting models to support a claim; sketching is not an isolated activity but is used as a tool to support model-based reasoning in the discipline. Copyright © 2017 Cognitive Science Society, Inc.

The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment.

PubMed

Brockmeier, Erica K; Hodges, Geoff; Hutchinson, Thomas H; Butler, Emma; Hecker, Markus; Tollefsen, Knut Erik; Garcia-Reyero, Natalia; Kille, Peter; Becker, Dörthe; Chipman, Kevin; Colbourne, John; Collette, Timothy W; Cossins, Andrew; Cronin, Mark; Graystock, Peter; Gutsell, Steve; Knapen, Dries; Katsiadaki, Ioanna; Lange, Anke; Marshall, Stuart; Owen, Stewart F; Perkins, Edward J; Plaistow, Stewart; Schroeder, Anthony; Taylor, Daisy; Viant, Mark; Ankley, Gerald; Falciani, Francesco

2017-08-01

In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.

The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment

PubMed Central

Brockmeier, Erica K.; Hodges, Geoff; Hutchinson, Thomas H.; Butler, Emma; Hecker, Markus; Tollefsen, Knut Erik; Garcia-Reyero, Natalia; Kille, Peter; Becker, Dörthe; Chipman, Kevin; Colbourne, John; Collette, Timothy W.; Cossins, Andrew; Cronin, Mark; Graystock, Peter; Gutsell, Steve; Knapen, Dries; Katsiadaki, Ioanna; Lange, Anke; Marshall, Stuart; Owen, Stewart F.; Perkins, Edward J.; Plaistow, Stewart; Schroeder, Anthony; Taylor, Daisy; Viant, Mark; Ankley, Gerald; Falciani, Francesco

2017-01-01

Abstract In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework. PMID:28525648

Molecular Testing of 163 Patients with Morquio A (Mucopolysaccharidosis IVA) Identifies 39 Novel GALNS Mutations

PubMed Central

Morrone, A; Tylee, K.L.; Al-Sayed, M; Brusius-Facchin, A.C.; Caciotti, A.; Church, H.J.; Coll, M.J.; Davidson, K.; Fietz, M.J.; Gort, L.; Hegde, M.; Kubaski, F.; Lacerda, L.; Laranjeira, F.; Leistner-Segal, S.; Mooney, S.; Pajares, S.; Pollard, L.; Riberio, I.; Wang, R.Y.; Miller, N.

2014-01-01

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles produce protein with decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided. PMID:24726177

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles.

PubMed

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F; Perez, Danny

2017-10-21

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles

NASA Astrophysics Data System (ADS)

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F.; Perez, Danny

2017-10-01

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Structural and spectroscopic investigation of glycinium oxalurate

NASA Astrophysics Data System (ADS)

Kavitha, T.; Pasupathi, G.; Marchewka, M. K.; Anbalagan, G.; Kanagathara, N.

2017-09-01

Glycinium oxalurate (GO) single crystals has been synthesized and grown by the slow solvent evaporation method at room temperature. Single crystal X-ray diffraction study confirms that GO crystal crystallizes in the monoclinic system with centrosymmetric space group P121/c1. The grown crystals are built up from single protonated glycinium residues and single dissociated oxalurate anions. A combination of ionic and donor-acceptor hydrogen-bond interactions linking together the glycine and oxaluric acid residues forms a three-dimensional network. Hydrogen bonded network present in the crystal gives notable vibrational effect. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on HF and density functional theory B3LYP methods with 6-311++G(d,p) basis set. Frontier molecular orbital energies and other related electronic properties are calculated. The natural bonding orbital (NBO) charges have been calculated and interpreted. The molecular electrostatic potential map has been constructed and discussed in detail.

Diversity and Habitat Preferences of Cultivated and Uncultivated Aerobic Methanotrophic Bacteria Evaluated Based on pmoA as Molecular Marker

PubMed Central

Knief, Claudia

2015-01-01

Methane-oxidizing bacteria are characterized by their capability to grow on methane as sole source of carbon and energy. Cultivation-dependent and -independent methods have revealed that this functional guild of bacteria comprises a substantial diversity of organisms. In particular the use of cultivation-independent methods targeting a subunit of the particulate methane monooxygenase (pmoA) as functional marker for the detection of aerobic methanotrophs has resulted in thousands of sequences representing “unknown methanotrophic bacteria.” This limits data interpretation due to restricted information about these uncultured methanotrophs. A few groups of uncultivated methanotrophs are assumed to play important roles in methane oxidation in specific habitats, while the biology behind other sequence clusters remains still largely unknown. The discovery of evolutionary related monooxygenases in non-methanotrophic bacteria and of pmoA paralogs in methanotrophs requires that sequence clusters of uncultivated organisms have to be interpreted with care. This review article describes the present diversity of cultivated and uncultivated aerobic methanotrophic bacteria based on pmoA gene sequence diversity. It summarizes current knowledge about cultivated and major clusters of uncultivated methanotrophic bacteria and evaluates habitat specificity of these bacteria at different levels of taxonomic resolution. Habitat specificity exists for diverse lineages and at different taxonomic levels. Methanotrophic genera such as Methylocystis and Methylocaldum are identified as generalists, but they harbor habitat specific methanotrophs at species level. This finding implies that future studies should consider these diverging preferences at different taxonomic levels when analyzing methanotrophic communities. PMID:26696968

Linking Adverse Outcome Pathways to Dynamic Energy Budgets: A Conceptual Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, Cheryl; Nisbet, Roger; Antczak, Philipp

Ecological risk assessment quantifies the likelihood of undesirable impacts of stressors, primarily at high levels of biological organization. Data used to inform ecological risk assessments come primarily from tests on individual organisms or from suborganismal studies, indicating a disconnect between primary data and protection goals. We know how to relate individual responses to population dynamics using individual-based models, and there are emerging ideas on how to make connections to ecosystem services. However, there is no established methodology to connect effects seen at higher levels of biological organization with suborganismal dynamics, despite progress made in identifying Adverse Outcome Pathways (AOPs) thatmore » link molecular initiating events to ecologically relevant key events. This chapter is a product of a working group at the National Center for Mathematical and Biological Synthesis (NIMBioS) that assessed the feasibility of using dynamic energy budget (DEB) models of individual organisms as a “pivot” connecting suborganismal processes to higher level ecological processes. AOP models quantify explicit molecular, cellular or organ-level processes, but do not offer a route to linking sub-organismal damage to adverse effects on individual growth, reproduction, and survival, which can be propagated to the population level through individual-based models. DEB models describe these processes, but use abstract variables with undetermined connections to suborganismal biology. We propose linking DEB and quantitative AOP models by interpreting AOP key events as measures of damage-inducing processes in a DEB model. Here, we present a conceptual model for linking AOPs to DEB models and review existing modeling tools available for both AOP and DEB.« less

Complex Homology and the Evolution of Nervous Systems

PubMed Central

Liebeskind, Benjamin J.; Hillis, David M.; Zakon, Harold H.; Hofmann, Hans A.

2016-01-01

We examine the complex evolution of animal nervous systems and discuss the ramifications of this complexity for inferring the nature of early animals. Although reconstructing the origins of nervous systems remains a central challenge in biology, and the phenotypic complexity of early animals remains controversial, a compelling picture is emerging. We now know that the nervous system and other key animal innovations contain a large degree of homoplasy, at least on the molecular level. Conflicting hypotheses about early nervous system evolution are due primarily to differences in the interpretation of this homoplasy. We highlight the need for explicit discussion of assumptions and discuss the limitations of current approaches for inferring ancient phenotypic states. PMID:26746806

Navigating the network: signaling cross-talk in hematopoietic cells

PubMed Central

Fraser, Iain D C; Germain, Ronald N

2009-01-01

Recent studies in hematopoietic cells have led to a growing appreciation of the diverse modes of molecular and functional cross-talk between canonical signaling pathways. However, these intersections represent only the tip of the iceberg. Emerging global analytical methods are providing an even richer and more complete picture of the many components that measurably interact in a network manner to produce cellular responses. Here we highlight the pieces in this Focus, emphasize the limitations of the present canonical pathway paradigm, and discuss the value of a systems biology approach using more global, quantitative experimental design and data analysis strategies. Lastly, we urge caution about overly facile interpretation of genome- and proteome-level studies. PMID:19295628

Single molecule data under scrutiny. Comment on "Extracting physics of life at the molecular level: A review of single-molecule data analyses" by W. Colomb & S.K. Sarkar

NASA Astrophysics Data System (ADS)

Wohland, Thorsten

2015-06-01

Single Molecule Detection and Spectroscopy have grown from their first beginnings into mainstream, mature research areas that are widely applied in the biological sciences. However, despite the advances in technology and the application of many single molecule techniques even in in vivo settings, the data analysis of single molecule experiments is complicated by noise, systematic errors, and complex underlying processes that are only incompletely understood. Colomb and Sarkar provide in this issue an overview of single molecule experiments and the accompanying problems in data analysis, which have to be overcome for a proper interpretation of the experiments [1].

Distribution of molecular weight in glyceride polymerizates or aggregates of them after contact with lunar grains

NASA Technical Reports Server (NTRS)

Asunmaa, S. K.; Haack, R.

1977-01-01

An attempt is made to report on experiments in which a molecular-weight increase was determined in thin layers of triglyceride-containing glycerides after thin-layer contact for two years with lunar topsoil grains at 25 C without any thermal activation. It is noted that solidification was observed on both dielectric grains and metal-rich areas and that changes in viscosity and molecular weights were first detected by solidification of surface layers. Gel permeation chromatography is described which detected a general shift of the Gaussian distribution of the molecular-weight data toward generally higher molecular weights as well as an increase in mean molecular weight. Reaction mechanisms are considered, and results of spectrographic analysis are cited which support the interpretations of the molecular-weight data.

Psychological Testing of Sign Language Interpreters

ERIC Educational Resources Information Center

Seal, Brenda C.

2004-01-01

Twenty-eight sign language interpreters participated in a battery of tests to determine if a profile of cognitive, motor, attention, and personality attributes might distinguish them as a group and at different credential levels. Eight interpreters held Level II and nine held Level III Virginia Quality Assurance Screenings (VQAS); the other 11…

[Clinical importance of thyroid gland cytology].

PubMed

Ting, S; Synoracki, S; Bockisch, A; Führer, D; Schmid, K W

2015-11-01

The cytological evaluation of fine needle biopsies (FNB) of the thyroid gland crucially depends on a close cooperation between clinicians and cytopathologists. Scintigraphy, sonography as well as clinical data and patient history are necessary for a correct interpretation of the indications for FNB; moreover, these data are of outstanding importance for cytopathologists for the correct interpretation of the cytomorphological findings. This overview describes the present standards in the acquisition, technical workup and cytopathological interpretation of thyroid gland tissue obtained by FNB, particularly focusing on the rapidly growing relevance of additional molecular pathological investigations to increase the diagnostic accuracy of thyroid FNB.

Uncertainty in the Timing of Origin of Animals and the Limits of Precision in Molecular Timescales

PubMed Central

dos Reis, Mario; Thawornwattana, Yuttapong; Angelis, Konstantinos; Telford, Maximilian J.; Donoghue, Philip C.J.; Yang, Ziheng

2015-01-01

Summary The timing of divergences among metazoan lineages is integral to understanding the processes of animal evolution, placing the biological events of species divergences into the correct geological timeframe. Recent fossil discoveries and molecular clock dating studies have suggested a divergence of bilaterian phyla >100 million years before the Cambrian, when the first definite crown-bilaterian fossils occur. Most previous molecular clock dating studies, however, have suffered from limited data and biases in methodologies, and virtually all have failed to acknowledge the large uncertainties associated with the fossil record of early animals, leading to inconsistent estimates among studies. Here we use an unprecedented amount of molecular data, combined with four fossil calibration strategies (reflecting disparate and controversial interpretations of the metazoan fossil record) to obtain Bayesian estimates of metazoan divergence times. Our results indicate that the uncertain nature of ancient fossils and violations of the molecular clock impose a limit on the precision that can be achieved in estimates of ancient molecular timescales. For example, although we can assert that crown Metazoa originated during the Cryogenian (with most crown-bilaterian phyla diversifying during the Ediacaran), it is not possible with current data to pinpoint the divergence events with sufficient accuracy to test for correlations between geological and biological events in the history of animals. Although a Cryogenian origin of crown Metazoa agrees with current geological interpretations, the divergence dates of the bilaterians remain controversial. Thus, attempts to build evolutionary narratives of early animal evolution based on molecular clock timescales appear to be premature. PMID:26603774

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.

PubMed

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

2012-03-28

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 the importance of a quantum chemical description of the hyperpolarizability tensor elements of the methyl group. © 2012 IOP Publishing Ltd

Genetic effects on gene expression across human tissues

PubMed Central

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease. PMID:29022597

Environmental statistics and optimal regulation

NASA Astrophysics Data System (ADS)

Sivak, David; Thomson, Matt

2015-03-01

The precision with which an organism can detect its environment, and the timescale for and statistics of environmental change, will affect the suitability of different strategies for regulating protein levels in response to environmental inputs. We propose a general framework--here applied to the enzymatic regulation of metabolism in response to changing nutrient concentrations--to predict the optimal regulatory strategy given the statistics of fluctuations in the environment and measurement apparatus, and the costs associated with enzyme production. We find: (i) relative convexity of enzyme expression cost and benefit influences the fitness of thresholding or graded responses; (ii) intermediate levels of measurement uncertainty call for a sophisticated Bayesian decision rule; and (iii) in dynamic contexts, intermediate levels of uncertainty call for retaining memory of the past. Statistical properties of the environment, such as variability and correlation times, set optimal biochemical parameters, such as thresholds and decay rates in signaling pathways. Our framework provides a theoretical basis for interpreting molecular signal processing algorithms and a classification scheme that organizes known regulatory strategies and may help conceptualize heretofore unknown ones.

Genetic effects on gene expression across human tissues.

PubMed

Battle, Alexis; Brown, Christopher D; Engelhardt, Barbara E; Montgomery, Stephen B

2017-10-11

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Structure of single-supported DMPC lipid bilayer membranes as a function of hydration level studied by neutron reflectivity and Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Miskowiec, A.; Schnase, P.; Bai, M.; Taub, H.; Hansen, F. Y.; Dubey, M.; Singh, S.; Majewski, J.

2012-02-01

We have recently been investigating the diffusion of water on single-supported DMPC lipid bilayer membranes at different levels of hydration, using high-resolution quasielastic neutron scattering (QNS). To aid in the interpretation of these QNS studies, we have conducted neutron reflectivity (NR) measurements on SPEAR at LANSCE to characterize the structure of similarly prepared samples. Protonated DMPC membranes were deposited onto SiO2-coated Si(100) substrates and characterized by Atomic Force Microscopy (AFM) at different levels of hydration. We find reasonable agreement between the membrane thickness determined by NR and AFM at room temperature. We also find consistency between the scattering length density (SLD) profile in the vicinity of the upper leaflet of the supported DMPC membrane and that found in a molecular dynamics simulation of a freestanding membrane at 303 K. However, the fit to the reflectivity curve can be improved by modifying the SLD profile near the leaflet closest to the SiO2 surface.

Functional Dynamics of Hexameric Helicase Probed by Hydrogen Exchange and Simulation

PubMed Central

Radou, Gaël; Dreyer, Frauke N.; Tuma, Roman; Paci, Emanuele

2014-01-01

The biological function of large macromolecular assemblies depends on their structure and their dynamics over a broad range of timescales; for this reason, it is a significant challenge to investigate these assemblies using conventional experimental techniques. One of the most promising experimental techniques is hydrogen-deuterium exchange detected by mass spectrometry. Here, we describe to our knowledge a new computational method for quantitative interpretation of deuterium exchange kinetics and apply it to a hexameric viral helicase P4 that unwinds and translocates RNA into a virus capsid at the expense of ATP hydrolysis. Room-temperature dynamics probed by a hundred nanoseconds of all-atom molecular dynamics simulations is sufficient to predict the exchange kinetics of most sequence fragments and provide a residue-level interpretation of the low-resolution experimental results. The strategy presented here is also a valuable tool to validate experimental data, e.g., assignments, and to probe mechanisms that cannot be observed by x-ray crystallography, or that occur over timescales longer than those that can be realistically simulated, such as the opening of the hexameric ring. PMID:25140434

Quantum chemical studies on structural, vibrational, nonlinear optical properties and chemical reactivity of indigo carmine dye

NASA Astrophysics Data System (ADS)

El-Mansy, M. A. M.

2017-08-01

Structural and vibrational spectroscopic studies were performed on indigo carmine (IC) isomers using FT-IR spectral analysis along with DFT/B3LYP method utilizing Gaussian 09 software. GaussView 5 program has been employed to perform a detailed interpretation of vibrational spectra. Simulation of infrared spectra has led to an excellent overall agreement with the observed spectral patterns. Mulliken population analyses on atomic charges, MEP, HOMO-LUMO, NLO, first order hyperpolarizability and thermodynamic properties have been examined by (DFT/B3LYP) method with the SDD basis set level. Density of state spectra (DOS) were calculated using GaussSum 3 at the same level of theory. Molecular modeling approved that DOS Spectra are the most significant tools for differentiating between two IC isomers so far. Moreover, The IC isomers (cis-isomer) have shown an extended applicability for manufacturing both NLO and photovoltaic devices such as solar cells.

Fractal evaluation of drug amorphicity from optical and scanning electron microscope images

NASA Astrophysics Data System (ADS)

Gavriloaia, Bogdan-Mihai G.; Vizireanu, Radu C.; Neamtu, Catalin I.; Gavriloaia, Gheorghe V.

2013-09-01

Amorphous materials are metastable, more reactive than the crystalline ones, and have to be evaluated before pharmaceutical compound formulation. Amorphicity is interpreted as a spatial chaos, and patterns of molecular aggregates of dexamethasone, D, were investigated in this paper by using fractal dimension, FD. Images having three magnifications of D were taken from an optical microscope, OM, and with eight magnifications, from a scanning electron microscope, SEM, were analyzed. The average FD for pattern irregularities of OM images was 1.538, and about 1.692 for SEM images. The FDs of the two kinds of images are less sensitive of threshold level. 3D images were shown to illustrate dependence of FD of threshold and magnification level. As a result, optical image of single scale is enough to characterize the drug amorphicity. As a result, the OM image at a single scale is enough to characterize the amorphicity of D.

Multifaceted origins of sex differences in the brain

PubMed Central

2016-01-01

Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue. PMID:26833829

[Eco-epidemiology: towards epidemiology of complexity].

PubMed

Bizouarn, Philippe

2016-05-01

In order to solve public health problems posed by the epidemiology of risk factors centered on the individual and neglecting the causal processes linking the risk factors with the health outcomes, Mervyn Susser proposed a multilevel epidemiology called eco-epidemiology, addressing the interdependence of individuals and their connection with molecular, individual, societal, environmental levels of organization participating in the causal disease processes. The aim of this epidemiology is to integrate more than a level of organization in design, analysis and interpretation of health problems. After presenting the main criticisms of risk-factor epidemiology focused on the individual, we will try to show how eco-epidemiology and its development could help to understand the need for a broader and integrative epidemiology, in which studies designed to identify risk factors would be balanced by studies designed to answer other questions equally vital to public health. © 2016 médecine/sciences – Inserm.

[Post-mortem microbiology analysis].

PubMed

Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

2013-12-01

Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. Crown Copyright © 2012. Published by Elsevier Espana. All rights reserved.

Speciation in ancient cryptic species complexes: evidence from the molecular phylogeny of Brachionus plicatilis (Rotifera).

PubMed

Gómez, Africa; Serra, Manuel; Carvalho, Gary R; Lunt, David H

2002-07-01

Continental lake-dwelling zooplanktonic organisms have long been considered cosmopolitan species with little geographic variation in spite of the isolation of their habitats. Evidence of morphological cohesiveness and high dispersal capabilities support this interpretation. However, this view has been challenged recently as many such species have been shown either to comprise cryptic species complexes or to exhibit marked population genetic differentiation and strong phylogeographic structuring at a regional scale. Here we investigate the molecular phylogeny of the cosmopolitan passively dispersing rotifer Brachionus plicatilis (Rotifera: Monogononta) species complex using nucleotide sequence variation from both nuclear (ribosomal internal transcribed spacer 1, ITS1) and mitochondrial (cytochrome c oxidase subunit I, COI) genes. Analysis of rotifer resting eggs from 27 salt lakes in the Iberian Peninsula plus lakes from four continents revealed nine genetically divergent lineages. The high level of sequence divergence, absence of hybridization, and extensive sympatry observed support the specific status of these lineages. Sequence divergence estimates indicate that the B. plicatilis complex began diversifying many millions of years ago, yet has showed relatively high levels of morphological stasis. We discuss these results in relation to the ecology and genetics of aquatic invertebrates possessing dispersive resting propagules and address the apparent contradiction between zooplanktonic population structure and their morphological stasis.

Collaborative Research: Nanopore Confinement of C-H-O Mixed Volatile Fluids Relevant to Subsurface Energy Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grady, Brian P.

2015-03-11

The scientific objective of this proposal was to obtain a fundamental atomic- to macro-scale understanding of the sorptivity, structure and dynamics of simple and complex hydrocarbon (HC) fluids at mineral surfaces or within nanoporous matrices over temperatures, pressures and compositions encountered in near-surface and shallow crustal environments. The research supported by this award was complementary to that conducted by the group of Prof. David cole at Ohio State University. The scope of the present award was to utilize molecular-level modeling to provide critically important insights into the interfacial properties of mineral-volatile systems, assist in the interpretation of experimental data andmore » predict fluid behavior beyond the limits of current experimental capability. During the past three years the effort has focused primarily on the behavior of C-H volatiles including methane (CH 4) and propane (C 3H 8), mixed-volatile systems including hydrocarbon - CO 2 with and without H 2O present. The long-range goal is to quantitatively link structure, dynamics and reactivity in complex mineral-/C-H-O systems from the atomic to the molecular to the macroscopic levels. The results are relevant to areas of growing importance such as gas shale, HC-bearing hydrothermal systems, and CO 2 storage.« less

Importance and pitfalls of molecular analysis to parasite epidemiology.

PubMed

Constantine, Clare C

2003-08-01

Molecular tools are increasingly being used to address questions about parasite epidemiology. Parasites represent a diverse group and they might not fit traditional population genetic models. Testing hypotheses depends equally on correct sampling, appropriate tool and/or marker choice, appropriate analysis and careful interpretation. All methods of analysis make assumptions which, if violated, make the results invalid. Some guidelines to avoid common pitfalls are offered here.

TANDEM: a two-stage approach to maximize interpretability of drug response models based on multiple molecular data types.

PubMed

Aben, Nanne; Vis, Daniel J; Michaut, Magali; Wessels, Lodewyk F A

2016-09-01

Clinical response to anti-cancer drugs varies between patients. A large portion of this variation can be explained by differences in molecular features, such as mutation status, copy number alterations, methylation and gene expression profiles. We show that the classic approach for combining these molecular features (Elastic Net regression on all molecular features simultaneously) results in models that are almost exclusively based on gene expression. The gene expression features selected by the classic approach are difficult to interpret as they often represent poorly studied combinations of genes, activated by aberrations in upstream signaling pathways. To utilize all data types in a more balanced way, we developed TANDEM, a two-stage approach in which the first stage explains response using upstream features (mutations, copy number, methylation and cancer type) and the second stage explains the remainder using downstream features (gene expression). Applying TANDEM to 934 cell lines profiled across 265 drugs (GDSC1000), we show that the resulting models are more interpretable, while retaining the same predictive performance as the classic approach. Using the more balanced contributions per data type as determined with TANDEM, we find that response to MAPK pathway inhibitors is largely predicted by mutation data, while predicting response to DNA damaging agents requires gene expression data, in particular SLFN11 expression. TANDEM is available as an R package on CRAN (for more information, see http://ccb.nki.nl/software/tandem). m.michaut@nki.nl or l.wessels@nki.nl Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Saturn meteorology - A diagnostic assessment of thin-layer configurations for the zonal flow

NASA Technical Reports Server (NTRS)

Allison, M.; Stone, P. H.

1983-01-01

Voyager imaging, infrared, and radio observations for Saturn have been recently interpreted by Smith et al. (1982) as an indication that the jet streams observed at the cloud tops extend to depths greater than the 10,000-bar level. This analysis assumes a maximum latitudinal temperature contrast of a few percent, a mean atmospheric rotation rate at depth given by Saturn's ratio period, and no variation with latitude of the bottom pressure level for the zonal flow system. These assumptions are not, however, firmly constrained by observation. The diagnostic analysis of plausible alternative configurations for Saturn's atmospheric structure demonstrates that a thin weather layer system (confined at mid to high latitudes to levels above 200 bar) cannot be excluded by any of the available observations. A quantitative estimate of the effects of moisture condensation (including the differentiation of mean molecular weight) suggests that these might provide the buoyancy contrasts necessary to support a thin-layer flow provided that Saturn's outer envelope is enriched approximately 10 times in water abundance relative to a solar composition atmosphere and strongly differentiated with latitude at the condensation level.

Toxicogenomics: the challenges and opportunities to identify biomarkers, signatures and thresholds to support mode-of-action.

PubMed

Currie, Richard A

2012-08-15

Toxicogenomics (TGx) can be defined as the application of "omics" techniques to toxicology and risk assessment. By identifying molecular changes associated with toxicity, TGx data might assist hazard identification and investigate causes. Early technical challenges were evaluated and addressed by consortia (e.g. ISLI/HESI and the Microarray Quality Control consortium), which demonstrated that TGx gave reliable and reproducible information. The MAQC also produced "best practice on signature generation" after conducting an extensive evaluation of different methods on common datasets. Two findings of note were the need for methods that control batch variability, and that the predictive ability of a signature changes in concert with the variability of the endpoint. The key challenge remaining is data interpretation, because TGx can identify molecular changes that are causal, associated with or incidental to toxicity. Application of Bradford Hill's tests for causation, which are used to build mode of action (MOA) arguments, can produce reasonable hypotheses linking altered pathways to phenotypic changes. However, challenges in interpretation still remain: are all pathway changes equal, which are most important and plausibly linked to toxicity? Therefore the expert judgement of the toxicologist is still needed. There are theoretical reasons why consistent alterations across a metabolic pathway are important, but similar changes in signalling pathways may not alter information flow. At the molecular level thresholds may be due to the inherent properties of the regulatory network, for example switch-like behaviours from some network motifs (e.g. positive feedback) in the perturbed pathway leading to the toxicity. The application of systems biology methods to TGx data can generate hypotheses that explain why a threshold response exists. However, are we adequately trained to make these judgments? There is a need for collaborative efforts between regulators, industry and academia to properly define how these technologies can be applied using appropriate case-studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular Chemistry as Diagnostic tool for Starbursts and AGNs The Molecular ISM of NGC 4418

NASA Astrophysics Data System (ADS)

Monje, R. R.; Aalto, S.

We present a brief discussion of the statistical surveys of HCN, HNC, HCO+ and HC3N that are used to model the extreme environments in the nuclei of starbursts and AGNs. Molecular studies are particularly useful for probing the deeply enshrouded dusty nuclei of luminous infrared galaxies. Here we present NGC 4418 as an example, one of the closest LIRG with high obscuration of the inner region. The interpretation of the observed line ratios require parallel development of theoretical chemical and radiative transport models.

Computer aided drug design

NASA Astrophysics Data System (ADS)

Jain, A.

2017-08-01

Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.

Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research

PubMed Central

Ilić, Nataša; Pilarczyk, Götz; Lee, Jin-Ho; Logeswaran, Abiramy; Borroni, Aurora Paola; Krufczik, Matthias; Theda, Franziska; Waltrich, Nadine; Bestvater, Felix; Hildenbrand, Georg; Cremer, Christoph; Blank, Michael

2017-01-01

Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine. PMID:28956810

Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research.

PubMed

Hausmann, Michael; Ilić, Nataša; Pilarczyk, Götz; Lee, Jin-Ho; Logeswaran, Abiramy; Borroni, Aurora Paola; Krufczik, Matthias; Theda, Franziska; Waltrich, Nadine; Bestvater, Felix; Hildenbrand, Georg; Cremer, Christoph; Blank, Michael

2017-09-28

Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine.

Building New Bridges between In Vitro and In Vivo in Early Drug Discovery: Where Molecular Modeling Meets Systems Biology.

PubMed

Pearlstein, Robert A; McKay, Daniel J J; Hornak, Viktor; Dickson, Callum; Golosov, Andrei; Harrison, Tyler; Velez-Vega, Camilo; Duca, José

2017-01-01

Cellular drug targets exist within networked function-generating systems whose constituent molecular species undergo dynamic interdependent non-equilibrium state transitions in response to specific perturbations (i.e.. inputs). Cellular phenotypic behaviors are manifested through the integrated behaviors of such networks. However, in vitro data are frequently measured and/or interpreted with empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs-Haldane) relevant to isolated target populations. We propose that cells act as analog computers, "solving" sets of coupled "molecular differential equations" (i.e. represented by populations of interacting species)via "integration" of the dynamic state probability distributions among those populations. Disconnects between biochemical and functional/phenotypic assays (cellular/in vivo) may arise with targetcontaining systems that operate far from equilibrium, and/or when coupled contributions (including target-cognate partner binding and drug pharmacokinetics) are neglected in the analysis of biochemical results. The transformation of drug discovery from a trial-and-error endeavor to one based on reliable design criteria depends on improved understanding of the dynamic mechanisms powering cellular function/dysfunction at the systems level. Here, we address the general mechanisms of molecular and cellular function and pharmacological modulation thereof. We outline a first principles theory on the mechanisms by which free energy is stored and transduced into biological function, and by which biological function is modulated by drug-target binding. We propose that cellular function depends on dynamic counter-balanced molecular systems necessitated by the exponential behavior of molecular state transitions under non-equilibrium conditions, including positive versus negative mass action kinetics and solute-induced perturbations to the hydrogen bonds of solvating water versus kT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Theoretical molecular studies of astrophysical interest

NASA Technical Reports Server (NTRS)

Flynn, George

1991-01-01

When work under this grant began in 1974 there was a great need for state-to-state collisional excitation rates for interstellar molecules observed by radio astronomers. These were required to interpret observed line intensities in terms of local temperatures and densities, but, owing to lack of experimental or theoretical values, estimates then being used for this purpose ranged over several orders of magnitude. A problem of particular interest was collisional excitation of formaldehyde; Townes and Cheung had suggested that the relative size of different state-to-state rates (propensity rules) was responsible for the anomalous absorption observed for this species. We believed that numerical molecular scattering techniques (in particular the close coupling or coupled channel method) could be used to obtain accurate results, and that these would be computationally feasible since only a few molecular rotational levels are populated at the low temperatures thought to prevail in the observed regions. Such calculations also require detailed knowledge of the intermolecular forces, but we thought that those could also be obtained with sufficient accuracy by theoretical (quantum chemical) techniques. Others, notably Roy Gordon at Harvard, had made progress in solving the molecular scattering equations, generally using semi-empirical intermolecular potentials. Work done under this grant generalized Gordon's scattering code, and introduced the use of theoretical interaction potentials obtained by solving the molecular Schroedinger equation. Earlier work had considered only the excitation of a diatomic molecule by collisions with an atom, and we extended the formalism to include excitation of more general molecular rotors (e.g., H2CO, NH2, and H2O) and also collisions of two rotors (e.g., H2-H2).

Analyzing Students’ Level of Understanding on Kinetic Theory of Gases

NASA Astrophysics Data System (ADS)

Nurhuda, T.; Rusdiana, D.; Setiawan, W.

2017-02-01

The purpose of this research is to analysis students’ level of understanding on gas kinetic theory. The method used is descriptive analytic with 32 students at the 11th grade of one high school in Bandung city as a sample. The sample was taken using random sampling technique. Data collection tool used is an essay test with 23 questions. The instrument was used to identify students’ level of understanding and was judged by four expert judges before it was employed, from 27 questions become to 23 questions, for data collection. Questions used are the conceptual understanding including the competence to explain, extrapolate, translate and interpret. Kinetic theory of gases section that was tested includes ideal gas law, kinetic molecular theory and equipartition of energy. The result shows from 0-4 level of understanding, 19% of the students have partial understanding on the 3th level and 81% of them have partial understanding with a specific misconception on 2th level. For the future research, it is suggested to overcome these conceptual understanding with an Interactive Lecture Demonstrations teaching model and coupled with some teaching materials based on multi-visualization because kinetic theory of gases is a microscopic concept.

Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against Methicillin Resistant Staphylococcus aureus.

PubMed

Kiem, Sungmin; Schentag, Jerome J

2014-12-01

Although antibiotics whose epithelial lining fluid (ELF) concentrations are reported high tend to be preferred in treatment of pneumonia, measurement of ELF concentrations of antibiotics could be misled by contamination from lysis of ELF cells and technical errors of bronchoalveolar lavage (BAL). In this review, ELF concentrations of anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics were interpreted considering above confounding factors. An equation used to explain antibiotic diffusion into CSF (cerebrospinal fluid) was adopted: ELF/free serum concentration ratio = 0.96 + 0.091 × ln (partition coefficient / molecular weight(1/2)). Seven anti-MRSA antibiotics with reported ELF concentrations were fitted to this equation to see if their ELF concentrations were explainable by the penetration capacity only. Then, outliers were modeled under the assumption of varying contamination from lysed ELF cells (test range 0-10% of ELF volume). ELF concentrations of oritavancin, telavancin, tigecycline, and vancomycin were well described by the diffusion equation, with or without additional impact from cell lysis. For modestly high ELF/free serum concentration ratio of linezolid, technical errors of BAL should be excluded. Although teicoplanin and iclaprim showed high ELF/free serum ratios also, their protein binding levels need to be cleared for proper interpretation. At the moment, it appears very premature to use ELF concentrations of anti-MRSA antibiotics as a relevant guide for treatment of lung infections by MRSA.

Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against Methicillin Resistant Staphylococcus aureus

PubMed Central

Schentag, Jerome J

2014-01-01

Although antibiotics whose epithelial lining fluid (ELF) concentrations are reported high tend to be preferred in treatment of pneumonia, measurement of ELF concentrations of antibiotics could be misled by contamination from lysis of ELF cells and technical errors of bronchoalveolar lavage (BAL). In this review, ELF concentrations of anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics were interpreted considering above confounding factors. An equation used to explain antibiotic diffusion into CSF (cerebrospinal fluid) was adopted: ELF/free serum concentration ratio = 0.96 + 0.091 × ln (partition coefficient / molecular weight1/2). Seven anti-MRSA antibiotics with reported ELF concentrations were fitted to this equation to see if their ELF concentrations were explainable by the penetration capacity only. Then, outliers were modeled under the assumption of varying contamination from lysed ELF cells (test range 0-10% of ELF volume). ELF concentrations of oritavancin, telavancin, tigecycline, and vancomycin were well described by the diffusion equation, with or without additional impact from cell lysis. For modestly high ELF/free serum concentration ratio of linezolid, technical errors of BAL should be excluded. Although teicoplanin and iclaprim showed high ELF/free serum ratios also, their protein binding levels need to be cleared for proper interpretation. At the moment, it appears very premature to use ELF concentrations of anti-MRSA antibiotics as a relevant guide for treatment of lung infections by MRSA. PMID:25566401

A novel knowledge-based system for interpreting complex engineering drawings: theory, representation, and implementation.

PubMed

Lu, Tong; Tai, Chiew-Lan; Yang, Huafei; Cai, Shijie

2009-08-01

We present a novel knowledge-based system to automatically convert real-life engineering drawings to content-oriented high-level descriptions. The proposed method essentially turns the complex interpretation process into two parts: knowledge representation and knowledge-based interpretation. We propose a new hierarchical descriptor-based knowledge representation method to organize the various types of engineering objects and their complex high-level relations. The descriptors are defined using an Extended Backus Naur Form (EBNF), facilitating modification and maintenance. When interpreting a set of related engineering drawings, the knowledge-based interpretation system first constructs an EBNF-tree from the knowledge representation file, then searches for potential engineering objects guided by a depth-first order of the nodes in the EBNF-tree. Experimental results and comparisons with other interpretation systems demonstrate that our knowledge-based system is accurate and robust for high-level interpretation of complex real-life engineering projects.

Cutibacterium acnes molecular typing: time to standardize the method.

PubMed

Dagnelie, M-A; Khammari, A; Dréno, B; Corvec, S

2018-03-12

The Gram-positive, anaerobic/aerotolerant bacterium Cutibacterium acnes is a commensal of healthy human skin; it is subdivided into six main phylogenetic groups or phylotypes: IA1, IA2, IB, IC, II and III. To decipher how far specific subgroups of C. acnes are involved in disease physiopathology, different molecular typing methods have been developed to identify these subgroups: i.e. phylotypes, clonal complexes, and types defined by single-locus sequence typing (SLST). However, as several molecular typing methods have been developed over the last decade, it has become a difficult task to compare the results from one article to another. Based on the scientific literature, the aim of this narrative review is to propose a standardized method to perform molecular typing of C. acnes, according to the degree of resolution needed (phylotypes, clonal complexes, or SLST types). We discuss the existing different typing methods from a critical point of view, emphasizing their advantages and drawbacks, and we identify the most frequently used methods. We propose a consensus algorithm according to the needed phylogeny resolution level. We first propose to use multiplex PCR for phylotype identification, MLST9 for clonal complex determination, and SLST for phylogeny investigation including numerous isolates. There is an obvious need to create a consensus about molecular typing methods for C. acnes. This standardization will facilitate the comparison of results between one article and another, and also the interpretation of clinical data. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Molecular structure, NMR, UV-Visible, vibrational spectroscopic and HOMO, LUMO analysis of (E)-1-(2, 6-bis (4-methoxyphenyl)-3, 3-dimethylpiperidine-4-ylidene)-2-(3-(3, 5-dimethyl-1H-pyrazol-1-yl) pyrazin-2-yl) hydrazine by DFT method

NASA Astrophysics Data System (ADS)

Alphonsa, A. Therasa; Loganathan, C.; Anand, S. Athavan Alias; Kabilan, S.

2016-02-01

We have synthesized (E)-1-(2, 6-bis (4-methoxyphenyl)-3, 3-dimethylpiperidine-4-ylidene)-2-(3-(3, 5-dimethyl-1H-pyrazol-1-yl) pyrazin-2-yl) hydrazine (PM6). It was characterized using FT-IR, FT-Raman, 1H NMR, 13C NMR techniques. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 09 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-311 G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated stretching frequencies have been found to be in good agreement with the experimental frequencies. The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and density of states (DOS). The absorption spectra have been computed by using time dependent density functional theory (TD-DFT). 1H and 13C NMR spectra were recorded and 1H and 13C NMR chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. From the optimized geometry of the molecule, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMOs) of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values.

Mirrored continuum and molecular scale simulations of the ignition of gamma phase RDX

NASA Astrophysics Data System (ADS)

Stewart, D. Scott; Chaudhuri, Santanu; Joshi, Kaushik; Lee, Kibaek

2017-01-01

We describe the ignition of an explosive crystal of gamma-phase RDX due to a thermal hot spot with reactive molecular dynamics (RMD), with first-principles trained, reactive force field based molecular potentials that represents an extremely complex reaction network. The RMD simulation is analyzed by sorting molecular product fragments into high and low molecular weight groups, to represent identifiable components that can be interpreted by a continuum model. A continuum model based on a Gibbs formulation has a single temperature and stress state for the mixture. The continuum simulation that mirrors the atomistic simulation allows us to study the atomistic simulation in the familiar physical chemistry framework and provides an essential, continuum/atomistic link.

Vibrational spectroscopic studies of Isoleucine by quantum chemical calculations.

PubMed

Moorthi, P P; Gunasekaran, S; Ramkumaar, G R

2014-04-24

In this work, we reported a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of Isoleucine (2-Amino-3-methylpentanoic acid). The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments, thermodynamics properties, NBO analyses, NMR chemical shifts and ultraviolet-visible spectral interpretation of Isoleucine have been studied by performing MP2 and DFT/cc-pVDZ level of theory. The FTIR, FT-Raman spectra were recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1) respectively. The UV-visible absorption spectra of the compound were recorded in the range of 200-800 nm. Computational calculations at MP2 and B3LYP level with basis set of cc-pVDZ is employed in complete assignments of Isoleucine molecule on the basis of the potential energy distribution (PED) of the vibrational modes, calculated using VEDA-4 program. The calculated wavenumbers are compared with the experimental values. The difference between the observed and calculated wavenumber values of most of the fundamentals is very small. (13)C and (1)H nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method and compared with experimental results. The formation of hydrogen bond was investigated in terms of the charge density by the NBO calculations. Based on the UV spectra and TD-DFT calculations, the electronic structure and the assignments of the absorption bands were carried out. Besides, molecular electrostatic potential (MEP) were investigated using theoretical calculations. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemistry of dense clumps near moving Herbig-Haro objects

NASA Astrophysics Data System (ADS)

Christie, H.; Viti, S.; Williams, D. A.; Girart, J. M.; Morata, O.

2011-09-01

Localized regions of enhanced emission from HCO+, NH3 and other species near Herbig-Haro objects (HHOs) have been interpreted as arising in a photochemistry stimulated by the HHO radiation on high-density quiescent clumps in molecular clouds. Static models of this process have been successful in accounting for the variety of molecular species arising ahead of the jet; however, recent observations show that the enhanced molecular emission is widespread along the jet as well as ahead. Hence, a realistic model must take into account the movement of the radiation field past the clump. It was previously unclear as to whether the short interaction time between the clump and the HHO in a moving source model would allow molecules such as HCO+ to reach high enough levels, and to survive for long enough to be observed. In this work we model a moving radiation source that approaches and passes a clump. The chemical picture is qualitatively unchanged by the addition of the moving source, strengthening the idea that enhancements are due to evaporation of molecules from dust grains. In addition, in the case of several molecules, the enhanced emission regions are longer lived. Some photochemically induced species, including methanol, are expected to maintain high abundances for ˜104 yr.

Molecular Dynamics Simulations Provide Atomistic Insight into Hydrogen Exchange Mass Spectrometry Experiments.

PubMed

Petruk, Ariel A; Defelipe, Lucas A; Rodríguez Limardo, Ramiro G; Bucci, Hernán; Marti, Marcelo A; Turjanski, Adrian G

2013-01-08

It is now clear that proteins are flexible entities that in solution switch between conformations to achieve their function. Hydrogen/Deuterium Exchange Mass Spectrometry (HX/MS) is an invaluable tool to understand dynamic changes in proteins modulated by cofactor binding, post-transductional modifications, or protein-protein interactions. ERK2MAPK, a protein involved in highly conserved signal transduction pathways of paramount importance for normal cellular function, has been extensively studied by HX/MS. Experiments of the ERK2MAPK in the inactive and active states (in the presence or absence of bound ATP) have provided valuable information on the plasticity of the MAPK domain. However, interpretation of the HX/MS data is difficult, and changes are mostly explained in relation to available X-ray structures, precluding a complete atomic picture of protein dynamics. In the present work, we have used all atom Molecular Dynamics simulations (MD) to provide a theoretical framework for the interpretation of HX/MS data. Our results show that detailed analysis of protein-solvent interaction along the MD simulations allows (i) prediction of the number of protons exchanged for each peptide in the HX/MS experiments, (ii) rationalization of the experimentally observed changes in exchange rates in different protein conditions at the residue level, and (iii) that at least for ERK2MAPK, most of the functionally observed differences in protein dynamics are related to what can be considered the native state conformational ensemble. In summary, the combination of HX/MS experiments with all atom MD simulations emerges as a powerful approach to study protein native state dynamics with atomic resolution.

Ab initio determination of geometries and vibrational characteristics of building blocks of organic super-conductors: TTF and its derivatives.

PubMed

Rani, P; Yadav, R A

2012-12-01

Molecular behavior of the building block {[2-(1,3-dithiole-2-ylidene)-1,3-dithiole] ≡ tetrathiafulvalene (TTF)} of organic superconductors have been investigated along with its three derivatives, namely, {[2-(1,3-dioxole-2-ylidene)-1,3-dioxole] ≡ tetraoxafulvalene (TOF)}; [2,2]-bi -[[1,3] oxathiolylidene] ≡ Der I and 2-(3H-Furan-2-ylidene)-[1,3] oxathiole ≡ Der II. The properties of the molecules such as molecular geometries, frontier MOs and vibrational spectra have been investigated by using DFT method at the B3LYP level employing 6-311++G(d,p) basis set. The geometrical parameters and atomic charges on various atomic sites of the TTF, TOF, Ders I and II suggest extended conjugation in these systems. The present calculations lead to the reassignments for of some of the fundamentals and new interpretations for some of the observed IR and Raman frequencies. One of the two modes involved in the Fermi resonance giving rise to the doublet 1555 and 1564 cm(-1) needed to be revised and another doublet 3083 and 3108 cm(-1) could be interpreted as a Fermi resonance doublet. Out of the two ν(C = C) modes under the a(1) species, the lower frequency mode is assigned to the ν(C = C) of the ring and the higher one to the ν(C = C) of the central C = C bond contrary to the assignment reported in literature. The conducting properties of these molecules depend mainly on this mode. Copyright © 2012 Elsevier B.V. All rights reserved.

Methodological flaws introduce strong bias into molecular analysis of microbial populations.

PubMed

Krakat, N; Anjum, R; Demirel, B; Schröder, P

2017-02-01

In this study, we report how different cell disruption methods, PCR primers and in silico analyses can seriously bias results from microbial population studies, with consequences for the credibility and reproducibility of the findings. Our results emphasize the pitfalls of commonly used experimental methods that can seriously weaken the interpretation of results. Four different cell lysis methods, three commonly used primer pairs and various computer-based analyses were applied to investigate the microbial diversity of a fermentation sample composed of chicken dung. The fault-prone, but still frequently used, amplified rRNA gene restriction analysis was chosen to identify common weaknesses. In contrast to other studies, we focused on the complete analytical process, from cell disruption to in silico analysis, and identified potential error rates. This identified a wide disagreement of results between applied experimental approaches leading to very different community structures depending on the chosen approach. The interpretation of microbial diversity data remains a challenge. In order to accurately investigate the taxonomic diversity and structure of prokaryotic communities, we suggest a multi-level approach combining DNA-based and DNA-independent techniques. The identified weaknesses of commonly used methods to study microbial diversity can be overcome by a multi-level approach, which produces more reliable data about the fate and behaviour of microbial communities of engineered habitats such as biogas plants, so that the best performance can be ensured. © 2016 The Society for Applied Microbiology.

An Alienation-Based Framework for Student Experience in Higher Education: New Interpretations of Past Observations in Student Learning Theory

ERIC Educational Resources Information Center

Barnhardt, Bradford; Ginns, Paul

2014-01-01

This article orients a recently proposed alienation-based framework for student learning theory (SLT) to the empirical basis of the approaches to learning perspective. The proposed framework makes new macro-level interpretations of an established micro-level theory, across three levels of interpretation: (1) a context-free psychological state…

Concordance in hippocampal and fecal Nr3c1 methylation is moderated by maternal behavior in the mouse

PubMed Central

Liberman, Shayna A; Mashoodh, Rahia; Thompson, Robert C; Dolinoy, Dana C; Champagne, Frances A

2012-01-01

Recent advances in genomic technologies now enable a reunion of molecular and evolutionary biology. Researchers investigating naturally living animal populations are thus increasingly able to capitalize upon genomic technologies to connect molecular findings with multiple levels of biological organization. Using this vertical approach in the laboratory, epigenetic gene regulation has emerged as an important mechanism integrating genotype and phenotype. To connect phenotype to population fitness, however, this same vertical approach must now be applied to naturally living populations. A major obstacle to studying epigenetics in noninvasive samples is tissue specificity of epigenetic marks. Here, using the mouse as a proof-of-principle model, we present the first known attempt to validate an epigenetic assay for use in noninvasive samples. Specifically, we compare DNA methylation of the NGFI-A (nerve growth factor-inducible protein A) binding site in the promoter of the glucocorticoid receptor (Nr3c1) gene between central (hippocampal) and peripheral noninvasive (fecal) tissues in juvenile Balb/c mice that had received varying levels of postnatal maternal care. Our results indicate that while hippocampal DNA methylation profiles correspond to maternal behavior, fecal DNA methylation levels do not. Moreover, concordance in methylation levels between these tissues within individuals only emerges after accounting for the effects of postnatal maternal care. Thus, although these findings may be specific to the Nr3c1 gene, we urge caution when interpreting DNA methylation patterns from noninvasive tissues, and offer suggestions for further research in this field. PMID:23301177

Interpretation bias in Cluster-C and borderline personality disorders.

PubMed

Arntz, Arnoud; Weertman, Anoek; Salet, Sjoerd

2011-08-01

Cognitive therapy (CT) assumes that personality disorders (PDs) are characterized by interpretational biases that maintain the disorder. Changing interpretations is therefore a major aim of CT of PDs. This study tested whether Borderline PD (BPD), Avoidant and Dependent PD (AV/DEPD), and Obsessive-Compulsive PD (OCPD) are characterized by specific interpretations. Among the 122 participants there were 55 PD patients (17 BPD, 30 AV/DEPD, 29 OCPD diagnoses), 26 axis-1 patients, and 41 nonpatients. Participants put themselves into 10 scripts of negative events and noted feelings, thoughts and behaviors that came to mind. Next, they chose between hypothesized BPD-specific, AV/DEPD-specific, and OCPD-specific interpretations of each event (forced choice). Lastly, participants rated belief in each interpretation. Regression analyses revealed that forced choices and belief ratings supported the CT-model of BPD and AV/DEP: interpretations were specific. The alleged OCPD-beliefs were however not specifically related to OCPD, with relatively high popularity in axis-1 patients and nonpatients. The open responses were classified by judges blind for diagnoses, with the following results. BPD was characterized by low levels of solution-focused and healthy-flexible/accepting responses, and higher levels of criticizing others and malevolent interpretations of others. AV/DEPD was characterized by lower levels of solution-focused responses, and higher levels of self-criticism, negative emotions, guilt and fear of judgment, as well as lower levels of other-criticism. OCPD only showed trends for lower healthy responses, and higher compulsiveness and worry. It is concluded that the assumptions of CT are supported for BPD and AV/DEPD, but not - at least not on the explicit interpretational level - for OCPD. CT of OCPD might need a slightly different approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structure and vibrational spectra of melaminium bis(trifluoroacetate) trihydrate: FT-IR, FT-Raman and quantum chemical calculations

NASA Astrophysics Data System (ADS)

Sangeetha, V.; Govindarajan, M.; Kanagathara, N.; Marchewka, M. K.; Gunasekaran, S.; Anbalagan, G.

Melaminium bis(trifluoroacetate) trihydrate (MTFA), an organic material has been synthesized and single crystals of MTFA have been grown by the slow solvent evaporation method at room temperature. X-ray powder diffraction analysis confirms that MTFA crystal belongs to the monoclinic system with space group P2/c. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on density functional theory (DFT) B3LYP method with 6-311G(d,p) and 6-311++G(d,p) basis sets. The X-ray diffraction data have been compared with the data of optimized molecular structure. The theoretical results show that the crystal structure can be reproduced by optimized geometry and the vibrational frequencies show good agreement with the experimental values. The nuclear magnetic resonance (NMR) chemical shift of the molecule has been calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. HOMO-LUMO, and other related molecular and electronic properties are calculated. The Mulliken and NBO charges have also been calculated and interpreted.

Ionic Mechanisms of Carbon Formation in Flames.

DTIC Science & Technology

1981-05-01

EFFECT OF MOLECULAR STRUCTURE ON INCIPIENT SOOT FORMATION, H.F. Calcote and D.M. Manos APPENDIX E: CORRELATION OF SOOT FORMATION IN TURBOJET ENGINES...future use by the Air Force of synfuels derived from coal, tar sands, and shale oil . These fuels are expected to have higher molecular weights, more...emissions and flame radiation from turbojet engines and larger scale combustors simulating practical engine conditions. b. Interpret and correlate the

Dynamics of crystalline acetanilide: Analysis using neutron scattering and computer simulation

NASA Astrophysics Data System (ADS)

Hayward, R. L.; Middendorf, H. D.; Wanderlingh, U.; Smith, J. C.

1995-04-01

The unusual temperature dependence of several optical spectroscopic vibrational bands in crystalline acetanilide has been interpreted as providing evidence for dynamic localization. Here we examine the vibrational dynamics of crystalline acetanilide over a spectral range of ˜20-4000 cm-1 using incoherent neutron scattering experiments, phonon normal mode calculations and molecular dynamics simulations. A molecular mechanics energy function is parametrized and used to perform the normal mode analyses in the full configurational space of the crystal i.e., including the intramolecular and intermolecular degrees of freedom. One- and multiphonon incoherent inelastic neutron scattering intensities are calculated from harmonic analyses in the first Brillouin zone and compared with the experimental data presented here. Phonon dispersion relations and mean-square atomic displacements are derived from the harmonic model and compared with data derived from coherent inelastic neutron scattering and neutron and x-ray diffraction. To examine the temperature effects on the vibrations the full, anharmonic potential function is used in molecular dynamics simulations of the crystal at 80, 140, and 300 K. Several, but not all, of the spectral features calculated from the molecular dynamics simulations exhibit temperature-dependent behavior in agreement with experiment. The significance of the results for the interpretation of the optical spectroscopic results and possible improvements to the model are discussed.

Transcriptional and catalytic responses of antioxidant and biotransformation pathways in mussels, Mytilus galloprovincialis, exposed to chemical mixtures.

PubMed

Giuliani, Maria Elisa; Benedetti, Maura; Arukwe, Augustine; Regoli, Francesco

2013-06-15

Antioxidant and biotransformation pathways are widely studied in marine organisms exposed to environmental stressors. However, mechanisms of responses and links between different intracellular levels are not always easy to elucidate and conflicting results are frequently observed between molecular and enzymatic data. In this study, transcriptional and catalytic responses of antioxidant and biotransformation parameters were analyzed after a 4-week exposure of a marine invertebrate, Mytilus galloprovincialis, to chemical mixtures from low polluted and highly polluted sediments. A significant, dose-dependent bioaccumulation was observed for polycyclic aromatic hydrocarbons, especially low molecular weight compounds. Among antioxidant defences, catalase and glutathione peroxidases did not exhibit variations in enzymatic activity, while the corresponding gene transcriptions were up- and down-regulated, respectively; unchanged mRNA levels of superoxide dismutase confirmed the non-synchronous pathways of variations for such antioxidants. Biotransformation responses also revealed inconsistent trends between transcriptional and catalytic variations of glutathione S-transferases, and a significant increase in mRNA levels for cytochrome P450 3A1. The overall results indicated that transcriptional responses might be sensitive but do not necessarily correspond to functional changes, being more useful as "exposure" rather than "effect" biomarkers. Data on gene transcription and catalytic activities should be carefully interpreted when assessing the impact of chemical pollutants and additional studies are needed on modulation of post-transcriptional mechanisms by environmental stressors. Copyright © 2013 Elsevier B.V. All rights reserved.

Probing the cellular damage in bacteria induced by GaN nanoparticles using confocal laser Raman spectroscopy

NASA Astrophysics Data System (ADS)

Sahoo, Prasana; Murthy, P. Sriyutha; Dhara, S.; Venugopalan, V. P.; Das, A.; Tyagi, A. K.

2013-08-01

Understanding the mechanism of nanoparticle (NP) induced toxicity in microbes is of potential importance to a variety of disciplines including disease diagnostics, biomedical implants, and environmental analysis. In this context, toxicity to bacterial cells and inhibition of biofilm formation by GaN NPs and their functional derivatives have been investigated against gram positive and gram negative bacterial species down to single cellular level. High levels of inhibition of biofilm formation (>80 %) was observed on treatments with GaN NPs at sub-micro molar concentrations. These results were substantiated with morphological features investigated with field emission scanning electron microscope, and the observed changes in vibrational modes of microbial cells using Raman spectroscopy. Raman spectra provided molecular interpretation of cell damage by registering signatures of molecular vibrations of individual living microbial cells and mapping the interplay of proteins at the cell membrane. As compared to the untreated cells, Raman spectra of NP-treated cells showed an increase in the intensities of characteristic protein bands, which confirmed membrane damage and subsequent release of cellular contents outside the cells. Raman spectral mapping at single cellular level can facilitate understanding of the mechanistic aspect of toxicity of GaN NPs. The effect may be correlated to passive diffusion causing mechanical damage to the membrane or ingress of Ga3+ (ionic radius 0.076 nm) which can potentially interfere with bacterial metabolism, as it resembles Fe2+ (ionic radius 0.077 nm), which is essential for energy metabolism.

Divergence of Iron Metabolism in Wild Malaysian Yeast

PubMed Central

Lee, Hana N.; Mostovoy, Yulia; Hsu, Tiffany Y.; Chang, Amanda H.; Brem, Rachel B.

2013-01-01

Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics. PMID:24142925

Divergence of iron metabolism in wild Malaysian yeast.

PubMed

Lee, Hana N; Mostovoy, Yulia; Hsu, Tiffany Y; Chang, Amanda H; Brem, Rachel B

2013-12-09

Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics.

Complex Homology and the Evolution of Nervous Systems.

PubMed

Liebeskind, Benjamin J; Hillis, David M; Zakon, Harold H; Hofmann, Hans A

2016-02-01

We examine the complex evolution of animal nervous systems and discuss the ramifications of this complexity for inferring the nature of early animals. Although reconstructing the origins of nervous systems remains a central challenge in biology, and the phenotypic complexity of early animals remains controversial, a compelling picture is emerging. We now know that the nervous system and other key animal innovations contain a large degree of homoplasy, at least on the molecular level. Conflicting hypotheses about early nervous system evolution are due primarily to differences in the interpretation of this homoplasy. We highlight the need for explicit discussion of assumptions and discuss the limitations of current approaches for inferring ancient phenotypic states. Copyright © 2015. Published by Elsevier Ltd.

Molecules as diagnostic tools in the interstellar medium

NASA Astrophysics Data System (ADS)

Spielfiedel, A.; Feautrier, N.; Balança, C.; Dayou, F.; Lique, F.; Senent, M.-L.

Analysis of light emission from different regions of the interstellar medium and circumstellar environments provides crucial information about the chemical composition and the physical conditions in these regions. Interpretation of the observed spectra requires the knowledge of collisional excitation rates as well as radiative rates participating to the line formation. In the first part, the paper focuses on collisional excitation rates of molecules relevant to the interstellar medium. It discusses currently available data and outlines new work carried out by the authors. Due to the use of accurate ab initio potential energy surfaces, the new rate coefficients differ significantly from previously published ones. In the second part, it is analysed from two examples how the use of the new rate coefficients could lead to important changes in the interpretation of molecular emission emerging from molecular clouds.

Conformational interpretation of vescalagin and castalagin physicochemical properties.

PubMed

Vivas, Nicolas; Laguerre, Michel; Pianet de Boissel, Isabelle; Vivas de Gaulejac, Nathalie; Nonier, Marie-Françoise

2004-04-07

Vescalagin and castalagin are two diastereoisomers. The variability of their principal physicochemical properties, compared with their small structural differences, suggests important conformational variations. This study shows, experimentally, that vescalagin has a greater effect on polarity, oxidizability in solution, and thermodegradability than castalagin. Conformational analysis by molecular mechanics demonstrated that vescalagin was more hydrophilic and was more reactive to electrophilic reagents than castalagin. Experimental results were thus explained and demonstrated the distinct behaviors of vescalagin and castalagin. These results were attributed to the C1 position of the two compounds because vescalin and castalin have comparable characteristics. Experimental data were confirmed and interpreted by molecular mechanics. This work represents one of the first attempts to correlate conformation and the properties of phenolic compounds. This step constitutes a predictive method for the pharmacology or chemistry of new compounds.

Transition from direct to inverted charge transport Marcus regions in molecular junctions via molecular orbital gating

NASA Astrophysics Data System (ADS)

Yuan, Li; Wang, Lejia; Garrigues, Alvar R.; Jiang, Li; Annadata, Harshini Venkata; Anguera Antonana, Marta; Barco, Enrique; Nijhuis, Christian A.

2018-04-01

Solid-state molecular tunnel junctions are often assumed to operate in the Landauer regime, which describes essentially activationless coherent tunnelling processes. In solution, on the other hand, charge transfer is described by Marcus theory, which accounts for thermally activated processes. In practice, however, thermally activated transport phenomena are frequently observed also in solid-state molecular junctions but remain poorly understood. Here, we show experimentally the transition from the Marcus to the inverted Marcus region in a solid-state molecular tunnel junction by means of intra-molecular orbital gating that can be tuned via the chemical structure of the molecule and applied bias. In the inverted Marcus region, charge transport is incoherent, yet virtually independent of temperature. Our experimental results fit well to a theoretical model that combines Landauer and Marcus theories and may have implications for the interpretation of temperature-dependent charge transport measurements in molecular junctions.

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH).

PubMed

Porto, Graça; Brissot, Pierre; Swinkels, Dorine W; Zoller, Heinz; Kamarainen, Outi; Patton, Simon; Alonso, Isabel; Morris, Michael; Keeney, Steve

2016-04-01

Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE-related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines.

Dielectric spectroscopy in aqueous solutions of oligosaccharides: Experiment meets simulation

NASA Astrophysics Data System (ADS)

Weingärtner, Hermann; Knocks, Andrea; Boresch, Stefan; Höchtl, Peter; Steinhauser, Othmar

2001-07-01

We report the frequency-dependent complex dielectric permittivity of aqueous solutions of the homologous saccharides D(+)-glucose, maltose, and maltotriose in the frequency range 200 MHz⩽ν⩽20 GHz. For each solute, solutions having concentrations between 0.01 and 1 mol dm-3 were studied. In all measured spectra two dispersion/loss regions could be discerned. With the exception of the two most concentrated maltotriose solutions, a good description of the spectra by the superposition of two Debye processes was possible. The amplitudes and correlation times of the glucose and maltose solutions determined from fits of the experimental data were compared to those obtained in an earlier molecular dynamics study of such systems; the overall agreement between experiment and simulation is quite satisfactory. A dielectric component analysis of the simulation results permitted a more detailed assignment of the relaxation processes occurring on the molecular level. The physical picture emerging from this analysis is compared with traditional hydration models used in the interpretation of measured dielectric data. It is shown that the usual standard models do not capture an important contribution arising from cross terms due to dipolar interactions between solute and water, as well as between hydration water and bulk water. This finding suggests that conventional approaches to determine molecular dipole moments of the solutes may be problematic. This is certainly the case for solutes with small molecular dipole moments, but strong solute-solvent interactions, such as the saccharides studied here.

Differential Interaction of Antimicrobial Peptides with Lipid Structures Studied by Coarse-Grained Molecular Dynamics Simulations.

PubMed

Balatti, Galo E; Ambroggio, Ernesto E; Fidelio, Gerardo D; Martini, M Florencia; Pickholz, Mónica

2017-10-20

In this work; we investigated the differential interaction of amphiphilic antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid structures by means of extensive molecular dynamics simulations. By using a coarse-grained (CG) model within the MARTINI force field; we simulated the peptide-lipid system from three different initial configurations: (a) peptides in water in the presence of a pre-equilibrated lipid bilayer; (b) peptides inside the hydrophobic core of the membrane; and (c) random configurations that allow self-assembled molecular structures. This last approach allowed us to sample the structural space of the systems and consider cooperative effects. The peptides used in our simulations are aurein 1.2 and maculatin 1.1; two well-known antimicrobial peptides from the Australian tree frogs; and molecules that present different membrane-perturbing behaviors. Our results showed differential behaviors for each type of peptide seen in a different organization that could guide a molecular interpretation of the experimental data. While both peptides are capable of forming membrane aggregates; the aurein 1.2 ones have a pore-like structure and exhibit a higher level of organization than those conformed by maculatin 1.1. Furthermore; maculatin 1.1 has a strong tendency to form clusters and induce curvature at low peptide-lipid ratios. The exploration of the possible lipid-peptide structures; as the one carried out here; could be a good tool for recognizing specific configurations that should be further studied with more sophisticated methodologies.

Molecular mechanism for lipid flip-flops.

PubMed

Gurtovenko, Andrey A; Vattulainen, Ilpo

2007-12-06

Transmembrane lipid translocation (flip-flop) processes are involved in a variety of properties and functions of cell membranes, such as membrane asymmetry and programmed cell death. Yet, flip-flops are one of the least understood dynamical processes in membranes. In this work, we elucidate the molecular mechanism of pore-mediated transmembrane lipid translocation (flip-flop) acquired from extensive atomistic molecular dynamics simulations. On the basis of 50 successful flip-flop events resolved in atomic detail, we demonstrate that lipid flip-flops may spontaneously occur in protein-free phospholipid membranes under physiological conditions through transient water pores on a time scale of tens of nanoseconds. While the formation of a water pore is induced here by a transmembrane ion density gradient, the particular way by which the pore is formed is irrelevant for the reported flip-flop mechanism: the appearance of a transient pore (defect) in the membrane inevitably leads to diffusive translocation of lipids through the pore, which is driven by thermal fluctuations. Our findings strongly support the idea that the formation of membrane defects in terms of water pores is the rate-limiting step in the process of transmembrane lipid flip-flop, which, on average, requires several hours. The findings are consistent with available experimental and computational data and provide a view to interpret experimental observations. For example, the simulation results provide a molecular-level explanation in terms of pores for the experimentally observed fact that the exposure of lipid membranes to electric field pulses considerably reduces the time required for lipid flip-flops.

Synthesis, X-ray crystallography, spectroscopic (FT-IR, 1H &13C NMR and UV), computational (DFT/B3LYP) and enzymes inhibitory studies of 7-hydroximinocholest-5-en-3-ol acetate

NASA Astrophysics Data System (ADS)

Ahmad, Faheem; Parveen, Mehtab; Alam, Mahboob; Azaz, Shaista; Malla, Ali Mohammed; Alam, Mohammad Jane; Lee, Dong-Ung; Ahmad, Shabbir

2016-07-01

The present study reports the synthesis of 7-Hydroximinocholest-5-en-3-ol acetate (syn. 3β-acetoxycholest-5-en-7-one oxime; in general, steroidal oxime). The identity of steroidal molecule was confirmed by NMR, FT-IR, MS, CHN microanalysis and X-ray crystallography. DFT calculations on the titled molecule have been performed. The molecular structure and spectra interpreted by Gaussian hybrid computational analysis theory (B3LYP) are found to be in good correlation with the experimental data obtained from the various spectrophotometric techniques. The vibrational bands appearing in the FTIR are assigned with great accuracy using harmonic frequencies along with intensities and animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural atomic charges have been presented at the same level of theory. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The percentages of various interactions are pictorialized by fingerprint plots of Hirshfeld surface. Steroidal oxime exhibited promising inhibitory activity against acetylcholinesterase (AChE) as compared to the reference drug, tacrine. Molecular docking was performed to introduce steroidal molecules into the X-ray crystal structures of acetylcholinesterase at the active site to find out the probable binding mode. The results of molecular docking admitted that steroidal oxime may exhibit enzyme inhibitor activity.

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)

PubMed Central

Porto, Graça; Brissot, Pierre; Swinkels, Dorine W; Zoller, Heinz; Kamarainen, Outi; Patton, Simon; Alonso, Isabel; Morris, Michael; Keeney, Steve

2016-01-01

Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE-related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines. PMID:26153218

CO2 capture in amine solutions: modelling and simulations with non-empirical methods

NASA Astrophysics Data System (ADS)

Andreoni, Wanda; Pietrucci, Fabio

2016-12-01

Absorption in aqueous amine solutions is the most advanced technology for the capture of CO2, although suffering from drawbacks that do not allow exploitation on large scale. The search for optimum solvents has been pursued with empirical methods and has also motivated a number of computational approaches over the last decade. However, a deeper level of understanding of the relevant chemical reactions in solution is required so as to contribute to this effort. We present here a brief critical overview of the most recent applications of computer simulations using ab initio methods. Comparison of their outcome shows a strong dependence on the structural models employed to represent the molecular systems in solution and on the strategy used to simulate the reactions. In particular, the results of very recent ab initio molecular dynamics augmented with metadynamics are summarized, showing the crucial role of water, which has been so far strongly underestimated both in the calculations and in the interpretation of experimental data. Indications are given for advances in computational approaches that are necessary if meant to contribute to the rational design of new solvents.

Admixture analysis in relation to pedigree studies of introgression in a minority British cattle breed: the Lincoln Red.

PubMed

Bray, T C; Hall, S J G; Bruford, M W

2014-02-01

Investigation of historic population processes using molecular data has been facilitated by the use of approximate Bayesian computation (ABC), which enables the consideration of multiple alternative demographic scenarios. The Lincoln Red cattle breed provides a relatively simple example of two well-documented admixture events. Using molecular data for this breed, we found that structure did not resolve very low (<5% levels) of introgression, possibly due to sampling limitations. We evaluated the performance of two ABC approaches (2BAD and DIYABC) against those of two earlier methodologies, ADMIX and LEADMIX, by comparing their interpretations with the conclusions drawn from herdbook analysis. The ABC methods gave credible values for the proportions of the Lincoln Red genotype that are attributable to Aberdeen Angus and Limousin, although estimates of effective population size and event timing were not realistic. We suggest ABC methods are a valuable supplement to pedigree-based studies but that the accuracy of admixture determination is likely to diminish with increasing complexity of the admixture scenario. © 2013 Blackwell Verlag GmbH.

Hydrogen bonding as the origin of the switching behavior in dithiolated phenylene-vinylene oligomers

NASA Astrophysics Data System (ADS)

Obodo, J. T.; Gkionis, K.; Rungger, I.; Sanvito, S.; Schwingenschlögl, U.

2013-08-01

We investigate theoretically the switching behavior of a dithiolated phenylene-vinylene oligomer sandwiched between Au(111) electrodes using self-interaction corrected density-functional theory combined with the nonequilibrium Green's-function method for quantum transport. The molecule presents a configurational bistability, which can be exploited in constructing molecular memories, switches, and sensors. We find that protonation of the terminating thiol groups is at the origin of the change in conductance. H bonding at the thiol group weakens the S-Au bond and reduces by about one order of magnitude the transmission coefficient at the Fermi level, and thus the linear response conductance. Furthermore, protonation downshifts in energy the position of the highest occupied molecular orbital, so that the current of the protonated species is lower than that of the unprotonated one along the entire bias range investigated, from -1.5 to 1.5 V. A second protonation at the opposite thiol group has only minor effects and no further drastic reduction in transmission takes place. Our results allow us to re-interpret the experimental data originally attributing the conductance reduction to H dissociation.

Top-down approach to vestibular compensation: translational lessons from vestibular rehabilitation

PubMed Central

Balaban, Carey D.; Hoffer, Michael E.; Gottshall, Kim R.

2012-01-01

This review examines vestibular compensation and vestibular rehabilitation from a unified translational research perspective. Laboratory studies illustrate neurobiological principles of vestibular compensation at the molecular, cellular and systems levels in animal models that inform vestibular rehabilitation practice. However, basic research has been hampered by an emphasis on ‘naturalistic’ recovery, with time after insult and drug interventions as primary dependent variables. The vestibular rehabilitation literature, on the other hand, provides information on how the degree of compensation can be shaped by specific activity regimens. The milestones of the early spontaneous static compensation mark the re-establishment of static gaze stability, which provides a common coordinate frame for the brain to interpret residual vestibular information in the context of visual, somatosensory and visceral signals that convey gravitoinertial information. Stabilization of the head orientation and the eye orientation (suppression of spontaneous nystagmus) appear to be necessary by not sufficient conditions for successful rehabilitation, and define a baseline for initiating retraining. The lessons from vestibular rehabilitation in animal models offer the possibility of shaping the recovery trajectory to identify molecular and genetic factors that can improve vestibular compensation. PMID:22981400

A 400,000-year-old mitochondrial genome questions phylogenetic relationships amongst archaic hominins: using the latest advances in ancient genomics, the mitochondrial genome sequence of a 400,000-year-old hominin has been deciphered.

PubMed

Orlando, Ludovic

2014-06-01

By combining state-of-the-art approaches in ancient genomics, Meyer and co-workers have reconstructed the mitochondrial sequence of an archaic hominin that lived at Sierra de Atapuerca, Spain about 400,000 years ago. This achievement follows recent advances in molecular anthropology that delivered the genome sequence of younger archaic hominins, such as Neanderthals and Denisovans. Molecular phylogenetic reconstructions placed the Atapuercan as a sister group to Denisovans, although its morphology suggested closer affinities with Neanderthals. In addition to possibly challenging our interpretation of the fossil record, this study confirms that genomic information can be recovered from extremely damaged DNA molecules, even in the presence of significant levels of human contamination. Together with the recent characterization of a 700,000-year-old horse genome, this study opens the Middle Pleistocene to genomics, thereby extending the scope of ancient DNA to the last million years. © 2014 WILEY Periodicals, Inc.

Quantum descriptors for predictive toxicology of halogenated aliphatic hydrocarbons.

PubMed

Trohalaki, S; Pachter, R

2003-04-01

In order to improve Quantitative Structure-Activity Relationships (QSARs) for halogenated aliphatics (HA) and to better understand the biophysical mechanism of toxic response to these ubiquitous chemicals, we employ improved quantum-mechanical descriptors to account for HA electrophilicity. We demonstrate that, unlike the lowest unoccupied molecular orbital energy, ELUMO, which was previously used as a descriptor, the electron affinity can be systematically improved by application of higher levels of theory. We also show that employing the reciprocal of ELUMO, which is more consistent with frontier molecular orbital (FMO) theory, improves the correlations with in vitro toxicity data. We offer explanations based on FMO theory for a result from our previous work, in which the LUMO energies of HA anions correlated surprisingly well with in vitro toxicity data. Additional descriptors are also suggested and interpreted in terms of the accepted biophysical mechanism of toxic response to HAs and new QSARs are derived for various chemical categories that compose the data set employed. These alternate descriptors provide important insight and could benefit other classes of compounds where the biophysical mechanism of toxic response involves dissociative attachment.

A Clinical and Molecular Survey of 62 Cystic Fibrosis Patients from Umbria (Central Italy) Disclosing a High Frequency (2.4%) of the 2184insA Allele: Implications for Screening.

PubMed

Prontera, Paolo; Isidori, Ilenia; Mencarini, Valeria; Pennoni, Guido; Mencarelli, Amedea; Stangoni, Gabriela; Di Cara, Giuseppe; Verrotti, Alberto

2016-01-01

Genetic testing strategies and counseling in cystic fibrosis (CF) can be problematic due to its extreme allelic heterogeneity and the difficult clinical interpretation of rare variants. Since in a previous survey of Italian CF patients, Umbria (a small region with about 900,000 inhabitants) was excluded due to the low number of chromosomes tested (<50), we have performed a comprehensive retrospective clinical and molecular survey of 62 CF patients coming from this region. We have summarized all the genotypic and phenotypic data in a table, and we interviewed the older patients in order to obtain a comprehensive overview of their conditions. We found that the c.2052_2053insA (2184insA) variant, a class I mutation with high frequency in Eastern Europe but very rare in Italy, is the fourth most frequent allele in Umbria. The 2184insA variant was not included in the first-level regional screening, and we therefore suggest the implementation of this variant in the future. © 2016 S. Karger AG, Basel.

A report template for molecular genetic tests designed to improve communication between the clinician and laboratory.

PubMed

Scheuner, Maren T; Hilborne, Lee; Brown, Julie; Lubin, Ira M

2012-07-01

Errors are most likely to occur during the pre- and postanalytic phases of the genetic testing process, which can contribute to underuse, overuse, and misuse of genetic tests. To mitigate these errors, we created a template for molecular genetic test reports that utilizes the combined features of synoptic reporting and narrative interpretation. A variation of the Delphi consensus process with an expert panel was used to create a draft report template, which was further informed by focus group discussions with primary care physicians. There was agreement that molecular genetic test reports should present information in groupings that flow in a logical manner, and most participants preferred the following order of presentation: patient and physician information, test performed, test results and interpretation, guidance on next steps, and supplemental information. We define data elements for the report as "required," "optional," "possible," and "not necessary"; provide recommendations regarding the grouping of these data elements; and describe the ideal design of the report template, including the preferred order of the report sections, formatting of data, and length of the report. With input from key stakeholders and building upon prior work, we created a template for molecular genetic test reports designed to improve clinical decision making at the point of care. The template design should lead to more effective communication between the laboratory and ordering clinician. Studies are needed to assess the usefulness and effectiveness of molecular genetic test reports generated using this template.

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement.

PubMed

Domínguez, J; Boettger, E C; Cirillo, D; Cobelens, F; Eisenach, K D; Gagneux, S; Hillemann, D; Horsburgh, R; Molina-Moya, B; Niemann, S; Tortoli, E; Whitelaw, A; Lange, C

2016-01-01

The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

Implementing a modeling software for animated protein-complex interactions using a physics simulation library.

PubMed

Ueno, Yutaka; Ito, Shuntaro; Konagaya, Akihiko

2014-12-01

To better understand the behaviors and structural dynamics of proteins within a cell, novel software tools are being developed that can create molecular animations based on the findings of structural biology. This study proposes our method developed based on our prototypes to detect collisions and examine the soft-body dynamics of molecular models. The code was implemented with a software development toolkit for rigid-body dynamics simulation and a three-dimensional graphics library. The essential functions of the target software system included the basic molecular modeling environment, collision detection in the molecular models, and physical simulations of the movement of the model. Taking advantage of recent software technologies such as physics simulation modules and interpreted scripting language, the functions required for accurate and meaningful molecular animation were implemented efficiently.

Targeting the untargeted in molecular phenomics with structurally-selective ion mobility-mass spectrometry.

PubMed

May, Jody Christopher; Gant-Branum, Randi Lee; McLean, John Allen

2016-06-01

Systems-wide molecular phenomics is rapidly expanding through technological advances in instrumentation and bioinformatics. Strategies such as structural mass spectrometry, which utilizes size and shape measurements with molecular weight, serve to characterize the sum of molecular expression in biological contexts, where broad-scale measurements are made that are interpreted through big data statistical techniques to reveal underlying patterns corresponding to phenotype. The data density, data dimensionality, data projection, and data interrogation are all critical aspects of these approaches to turn data into salient information. Untargeted molecular phenomics is already having a dramatic impact in discovery science from drug discovery to synthetic biology. It is evident that these emerging techniques will integrate closely in broad efforts aimed at precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-scale modelling of supercapacitors: From molecular simulations to a transmission line model

NASA Astrophysics Data System (ADS)

Pean, C.; Rotenberg, B.; Simon, P.; Salanne, M.

2016-09-01

We perform molecular dynamics simulations of a typical nanoporous-carbon based supercapacitor. The organic electrolyte consists in 1-ethyl-3-methylimidazolium and hexafluorophosphate ions dissolved in acetonitrile. We simulate systems at equilibrium, for various applied voltages. This allows us to determine the relevant thermodynamic (capacitance) and transport (in-pore resistivities) properties. These quantities are then injected in a transmission line model for testing its ability to predict the charging properties of the device. The results from this macroscopic model are in good agreement with non-equilibrium molecular dynamics simulations, which validates its use for interpreting electrochemical impedance experiments.

The Basic Principles of FDG-PET/CT Imaging.

PubMed

Basu, Sandip; Hess, Søren; Nielsen Braad, Poul-Erik; Olsen, Birgitte Brinkmann; Inglev, Signe; Høilund-Carlsen, Poul Flemming

2014-10-01

Positron emission tomography (PET) imaging with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) forms the basis of molecular imaging. FDG-PET imaging is a multidisciplinary undertaking that requires close interdisciplinary collaboration in a broad team comprising physicians, technologists, secretaries, radio-chemists, hospital physicists, molecular biologists, engineers, and cyclotron technicians. The aim of this review is to provide a brief overview of important basic issues and considerations pivotal to successful patient examinations, including basic physics, instrumentation, radiochemistry, molecular and cell biology, patient preparation, normal distribution of tracer, and potential interpretive pitfalls. Copyright © 2014 Elsevier Inc. All rights reserved.

Interpretation of size-exclusion chromatography for the determination of molecular-size distribution of human immunoglobulins.

PubMed

Christians, S; Schluender, S; van Treel, N D; Behr-Gross, M-E

2016-01-01

Molecular-size distribution by size-exclusion chromatography (SEC) [1] is used for the quantification of unwanted aggregated forms in therapeutic polyclonal antibodies, referred to as human immunoglobulins (Ig) in the European Pharmacopoeia. Considering not only the requirements of the monographs for human normal Ig (0338, 0918 and 2788) [2-4], but also the general chapter on chromatographic techniques (2.2.46) [5], several chromatographic column types are allowed for performing this test. Although the EDQM knowledge database gives only 2 examples of suitable columns as a guide for the user, these monographs permit the use of columns with different lengths and diameters, and do not prescribe either particle size or pore size, which are considered key characteristics of SEC columns. Therefore, the columns used may differ significantly from each other with regard to peak resolution, potentially resulting in ambiguous peak identity assignment. In some cases, this may even lead to situations where the manufacturer and the Official Medicines Control Laboratory (OMCL) in charge of Official Control Authority Batch Release (OCABR) have differing molecular-size distribution profiles for aggregates of the same batch of Ig, even though both laboratories follow the requirements of the relevant monograph. In the present study, several formally acceptable columns and the peak integration results obtained therewith were compared. A standard size-exclusion column with a length of 60 cm and a particle size of 10 µm typically detects only 3 Ig fractions, namely monomers, dimers and polymers. This column type was among the first reliable HPLC columns on the market for this test and very rapidly became the standard for many pharmaceutical manufacturers and OMCLs for batch release testing. Consequently, the distribution of monomers, dimers and polymers was established as the basis for the interpretation of the results of the molecular-size distribution test in the relevant monographs. However, modern columns with a smaller particle size provide better resolution and also reveal a class of components designated here as oligomers. This publication addresses the interpretation of the SEC test for Ig with respect to the following questions: - how can molecular-size distribution tests benefit from the use of the most recent column technology without changing the sense of well-established quality parameters? - is it possible to mathematically define a way to interpret chromatograms generated with various column types with the same fractionation range but different resolution power? - how should oligomers be considered regarding compliance with compendial specifications?

Digging into the low molecular weight peptidome with the OligoNet web server.

PubMed

Liu, Youzhong; Forcisi, Sara; Lucio, Marianna; Harir, Mourad; Bahut, Florian; Deleris-Bou, Magali; Krieger-Weber, Sibylle; Gougeon, Régis D; Alexandre, Hervé; Schmitt-Kopplin, Philippe

2017-09-15

Bioactive peptides play critical roles in regulating many biological processes. Recently, natural short peptides biomarkers are drawing significant attention and are considered as "hidden treasure" of drug candidates. High resolution and high mass accuracy provided by mass spectrometry (MS)-based untargeted metabolomics would enable the rapid detection and wide coverage of the low-molecular-weight peptidome. However, translating unknown masses (<1 500 Da) into putative peptides is often limited due to the lack of automatic data processing tools and to the limit of peptide databases. The web server OligoNet responds to this challenge by attempting to decompose each individual mass into a combination of amino acids out of metabolomics datasets. It provides an additional network-based data interpretation named "Peptide degradation network" (PDN), which unravels interesting relations between annotated peptides and generates potential functional patterns. The ab initio PDN built from yeast metabolic profiling data shows a great similarity with well-known metabolic networks, and could aid biological interpretation. OligoNet allows also an easy evaluation and interpretation of annotated peptides in systems biology, and is freely accessible at https://daniellyz200608105.shinyapps.io/OligoNet/ .

HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events

PubMed Central

Buhler, Stéphane; Sanchez-Mazas, Alicia

2011-01-01

Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies. Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the genetic history of human populations, and that their analysis allows a more thorough investigation of human MHC molecular evolution. PMID:21408106

Quantum dot multiplexing for the profiling of cellular receptors

NASA Astrophysics Data System (ADS)

Lee-Montiel, Felipe T.; Li, Peter; Imoukhuede, P. I.

2015-11-01

The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine.The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine. Electronic supplementary information (ESI) available: Additional information of Qdot size, spectra, images of HUVEC, HDFa cells, confocal microscopy setting and colocalization analysis results. See DOI: 10.1039/c5nr01455g

Hybridization improved bacteria resistance in abalone: Evidence from physiological and molecular responses.

PubMed

Liang, Shuang; Luo, Xuan; You, Weiwei; Ke, Caihuan

2018-01-01

Hybridization is an effective way of improving germplasm in abalone, as it often generates benign traits in the hybrids. The hybrids of Haliotis discus hannai and H. gigantea have shown heterosis in terms of disease resistance than one or both parental species. In the present study, to elucidate the physiological and molecular mechanism of this heterosis, we analyzed the dynamic changes of several immune indexes including survival rate, total circulating haemocyte count (THC), phagocytic activity, reactive oxygen species level (ROS) and phenoloxidase activity (PO) in two parental species, H. discus hannai (DD) and H. gigantea (GG), and their reciprocal hybrids H. discus hannai ♀ × H. gigantea ♂ (DG), H. gigantea ♀ × H. discus hannai ♂ (GD) challenged with a mixture of Vibrio harveyi, V. alginolyticus and V. parahaemolyticus (which have been demonstrated to be pathogenic to abalone). Besides, we cloned and analyzed three important immune genes: heat shock protein 70 (hsp70), ferritin and cold shock domain protein (csdp) in H. discus hannai and H. gigantea, then further investigated their mRNA level changes in the four abalone genotypes after bacterial challenge. Results showed that these physiological and molecular parameters were significantly induced by bacterial exposure, and their changing patterns were obviously different between the four genotypes: (1) Survival rates of the two hybrids were higher than both parental species after bacterial exposure; (2) DG had higher THC than the other three genotypes; (3) Phagocytosis responded slower in the hybrids than in the parental species; (4) DD's ROS level was lower than the other three genotypes at 48 h post infection; (5) Phenoloxidase activity was lower in DD during the infection compared to the other genotypes; (6) mRNA levels of hsp70 and csdp, were always lower in at least one parental species (DD) than in the hybrids after the bacterial exposure. Results from this study indicate that the hybrids are more active or efficient in immune system function, hence they could effectively defense against a bacterial invasion, leading to higher survival rates after challenge. This study provides physiological and molecular evidences for interpreting the disease resistant heterosis in this abalone hybrid system, which could help us in a better understanding and utilization of heterosis in abalone aquaculture. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Study of the Liquid-Liquid Partitioning Process Using Reverse-Phase Liquid Chromatography: An Undergraduate Analytical Chemistry Experiment.

ERIC Educational Resources Information Center

Lochmuller, C. H.; And Others

1980-01-01

Presents an undergraduate analytical chemistry experiment that promotes an interpretation of the molecular aspects of solute partitioning, enhancing student understanding of separation science and liquid chromatography. (CS)

Dudley Herschbach: Chemical Reactions and Molecular Beams

Science.gov Websites

elementary reactions such as K + CH3I and K + Br2, where it became possible to correlate reaction dynamics been a pioneer in the measurement and theoretical interpretation of vector properties of reaction

Evolutionary anthropology and genes: investigating the genetics of human evolution from excavated skeletal remains.

PubMed

Anastasiou, Evilena; Mitchell, Piers D

2013-10-01

The development of molecular tools for the extraction, analysis and interpretation of DNA from the remains of ancient organisms (paleogenetics) has revolutionised a range of disciplines as diverse as the fields of human evolution, bioarchaeology, epidemiology, microbiology, taxonomy and population genetics. The paper draws attention to some of the challenges associated with the extraction and interpretation of ancient DNA from archaeological material, and then reviews the influence of paleogenetics on the field of human evolution. It discusses the main contributions of molecular studies to reconstructing the evolutionary and phylogenetic relationships between extinct hominins (human ancestors) and anatomically modern humans. It also explores the evidence for evolutionary changes in the genetic structure of anatomically modern humans in recent millennia. This breadth of research has led to discoveries that would never have been possible using traditional approaches to human evolution. Copyright © 2013 Elsevier B.V. All rights reserved.

Viscosity of Common Seed and Vegetable Oils

NASA Astrophysics Data System (ADS)

Wes Fountain, C.; Jennings, Jeanne; McKie, Cheryl K.; Oakman, Patrice; Fetterolf, Monty L.

1997-02-01

Viscosity experiments using Ostwald-type gravity flow viscometers are not new to the physical chemistry laboratory. Several physical chemistry laboratory texts (1 - 3) contain at least one experiment studying polymer solutions or other well-defined systems. Several recently published articles (4 - 8) indicated the continued interest in using viscosity measurements in the teaching lab to illustrate molecular interpretation of bulk phenomena. Most of these discussions and teaching experiments are designed around an extensive theory of viscous flow and models of molecular shape that allow a full data interpretation to be attempted. This approach to viscosity experiments may not be appropriate for all teaching situations (e.g., high schools, general chemistry labs, and nonmajor physical chemistry labs). A viscosity experiment is presented here that is designed around common seed and vegetable oils. With the importance of viscosity to foodstuffs (9) and the importance of fatty acids to nutrition (10), an experiment using these common, recognizable oils has broad appeal.

Abnormal characteristics of binary molecular clusters in DMSO–ethanol mixtures under external electric fields

NASA Astrophysics Data System (ADS)

Wu, Zhiyan; Huang, Kama

2018-05-01

For the nonlinearly phenomena on the dielectric properties of dimethyl sulfoxide (DMSO)-ethanol mixtures under a low intensity microwave field, we propose a conjecture that there exist some abnormal molecular clusters. To interpret the mechanism of abnormal phenomena and confirm our conjecture about the existence of abnormal molecular clusters, an in-depth investigation about the structure evolutions of (DMSO)m(C2H5OH)n (m = 0-4; n = 0-4; m + n ≤ 4) molecular clusters induced by external electric fields has been given by using density functional theory. The results show that there exist some binary molecular clusters with large cluster radii in mixtures, and some of them are unstable under exposure of electric fields. It implies that the existence of certain abnormal molecular clusters in DMSO-ethanol mixtures results in their abnormality of dielectric properties.

Studies on molecular structure, vibrational spectra and molecular docking analysis of 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate

NASA Astrophysics Data System (ADS)

Suresh, D. M.; Amalanathan, M.; Hubert Joe, I.; Bena Jothy, V.; Diao, Yun-Peng

2014-09-01

The molecular structure, vibrational analysis and molecular docking analysis of the 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate (MDDNAB) molecule have been carried out using FT-IR and FT-Raman spectroscopic techniques and DFT method. The equilibrium geometry, harmonic vibrational wave numbers, various bonding features have been computed using density functional method. The calculated molecular geometry has been compared with experimental data. The detailed interpretation of the vibrational spectra has been carried out by using VEDA program. The hyper-conjugative interactions and charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The simulated FT-IR and FT-Raman spectra satisfactorily coincide with the experimental spectra. The PES and charge analysis have been made. The molecular docking was done to identify the binding energy and the Hydrogen bonding with the cancer protein molecule.

The identification of selected vegetation types in Arizona through the photointerpretation of intermediate scale aerial photography. M.S. Thesis

NASA Technical Reports Server (NTRS)

Ross, G. F. (Principal Investigator)

1973-01-01

The author has identified the following significant results. Nine photography interpretation tests were performed with a total of 19 different interpreters. Three tests were conducted with black and white intermediate scale photography and six tests with color infrared intermediate scale photography. The black and white test results show that the interpretation of vegetation mapped at the association level of classification is reliable for all the classes used at 61%. The color infrared tests indicate that the association level of mapping is unsatisfactory for vegetation interpretation of classes 1 and 6. Students' t-test indicated that intermediate scale black and white photography is significantly better than this particular color infrared photography for the interpretation of southeastern Arizona vegetation mapped at the association level.

Diagnostics of Carbon Nanotube Formation in a Laser Produced Plume: An Investigation of the Metal Catalyst by Laser Ablation Atomic Fluorescence Spectroscopy

NASA Technical Reports Server (NTRS)

deBoer, Gary; Scott, Carl

2003-01-01

Carbon nanotubes, elongated molecular tubes with diameters of nanometers and lengths in microns, hold great promise for material science. Hopes for super strong light-weight material to be used in spacecraft design is the driving force behind nanotube work at JSC. The molecular nature of these materials requires the appropriate tools for investigation of their structure, properties, and formation. The mechanism of nanotube formation is of particular interest because it may hold keys to controlling the formation of different types of nanotubes and allow them to be produced in much greater quantities at less cost than is currently available. This summer's work involved the interpretation of data taken last summer and analyzed over the academic year. The work involved diagnostic studies of carbon nanotube formation processes occurring in a laser-produced plume. Laser ablation of metal doped graphite to produce a plasma plume in which carbon nanotubes self assemble is one method of making carbon nanotube. The laser ablation method is amenable to applying the techniques of laser spectroscopy, a powerful tool for probing the energies and dynamics of atomic and molecular species. The experimental work performed last summer involved probing one of the metal catalysts, nickel, by laser induced fluorescence. The nickel atom was studied as a function of oven temperature, probe laser wavelength, time after ablation, and position in the laser produced plume. This data along with previously obtained data on carbon was analyzed over the academic year. Interpretations of the data were developed this summer along with discussions of future work. The temperature of the oven in which the target is ablated greatly influences the amount of material ablated and the propagation of the plume. The ablation conditions and the time scale of atomic and molecular lifetimes suggest that initial ablation of the metal doped carbon target results in atomic and small molecular species. The metal atoms survive for several milliseconds while the gaseous carbon atoms and small molecules nucleate more rapidly. Additional experiments and the development of in situ methods for carbon nanotube detection would allow these results to be interpreted from the perspective of carbon nanotube formation.

Assessment of the level of agreement in the interpretation of plain radiographs of lumbar spondylosis among clinical physiotherapists in Ghana.

PubMed

Bello, Ajediran I; Ofori, Eric K; Alabi, Oluwasegun J; Adjei, David N

2014-03-29

Objective physical assessment of patients with lumbar spondylosis involves plain film radiographs (PFR) viewing and interpretation by the radiologists. Physiotherapists also routinely assess PFR within the scope of their practice. However, studies appraising the level of agreement of physiotherapists' PFR interpretation with radiologists are not common in Ghana. Forty-one (41) physiotherapists took part in the cross-sectional survey. An assessment guide was developed from findings of the interpretation of three PFR of patients with lumbar spondylosis by a radiologist. The three PFR were selected from a pool of different radiographs based on clarity, common visible pathological features, coverage body segments and short post production period. Physiotherapists were required to view the same PFR after which they were assessed with the assessment guide according to the number of features identified correctly or incorrectly. The score range on the assessment form was 0-24, interpreted as follow: 0-8 points (low), 9-16 points (moderate) and 17-24 points (high) levels of agreement. Data were analyzed using one sample t-test and fisher's exact test at α = 0.05. The mean score of interpretation for the physiotherapists was 12.7 ± 2.6 points compared to the radiologist's interpretation of 24 points (assessment guide). The physiotherapists' levels were found to be significantly associated with their academic qualification (p = 0.006) and sex (p = 0.001). However, their levels of agreement were not significantly associated with their age group (p = 0.098), work settings (p = 0.171), experience (p = 0.666), preferred PFR view (p = 0.088) and continuing education (p = 0.069). The physiotherapists' skills fall short of expectation for interpreting PFR of patients with lumbar spondylosis. The levels of agreement with radiologist's interpretation have no link with year of clinial practice, age, work settings and continuing education. Thus, routine PFR viewing techniques should be made a priority in physiotherapists' continuing professional education.

Hubby and Lewontin on Protein Variation in Natural Populations: When Molecular Genetics Came to the Rescue of Population Genetics.

PubMed

Charlesworth, Brian; Charlesworth, Deborah; Coyne, Jerry A; Langley, Charles H

2016-08-01

The 1966 GENETICS papers by John Hubby and Richard Lewontin were a landmark in the study of genome-wide levels of variability. They used the technique of gel electrophoresis of enzymes and proteins to study variation in natural populations of Drosophila pseudoobscura, at a set of loci that had been chosen purely for technical convenience, without prior knowledge of their levels of variability. Together with the independent study of human populations by Harry Harris, this seminal study provided the first relatively unbiased picture of the extent of genetic variability in protein sequences within populations, revealing that many genes had surprisingly high levels of diversity. These papers stimulated a large research program that found similarly high electrophoretic variability in many different species and led to statistical tools for interpreting the data in terms of population genetics processes such as genetic drift, balancing and purifying selection, and the effects of selection on linked variants. The current use of whole-genome sequences in studies of variation is the direct descendant of this pioneering work. Copyright © 2016 by the Genetics Society of America.

Two-dimensional functional molecular nanoarchitectures - Complementary investigations with scanning tunneling microscopy and X-ray spectroscopy

NASA Astrophysics Data System (ADS)

Klappenberger, Florian

2014-02-01

Functional molecular nanoarchitectures (FMNs) are highly relevant for the development of future nanotechnology devices. Profound knowledge about the atomically controlled construction of such nanoscale assemblies is an indispensable requirement to render the implementation of such components into a real product successful. For exploiting their full potential the architectures’ functionalities have to be characterized in detail including the ways to tailor them. In recent years a plethora of sophisticated constructs were fabricated touching a wide range of research topics. The present review summarizes important achievements of bottom-up fabricated, molecular nanostructures created on single crystal metal surfaces under ultra-high vacuum conditions. This selection focuses on examples where self-assembly mechanisms played a central role for their construction. Such systems, though typically quite complex, can be comprehensively understood by the STM+XS approach combining scanning tunneling microscopy (STM) with X-ray spectroscopy (XS) and being aided in the atomic interpretation by the appropriate theoretic analysis, often from density functional theory. The symbiosis of the techniques is especially fruitful because of the complementary character of the information accessed by the local microscopy and the space-averaging spectroscopy tools. STM delivers sub-molecular spatial-resolution, but suffers from limited sensitivity for the chemical and conformational states of the building-blocks. XS compensates these weaknesses with element- and moiety-specific data, which in turn would be hard to interpret with respect to structure formation without the topographic details revealed by STM. The united merit of this methodology allows detailed geometric information to be obtained and addresses both the electronic and chemical state of the complex organic species constituting such architectures. Thus, possible changes induced by the various processes such as surface interaction, thermal annealing, or molecular recognition can be followed with unprecedented level of detail. The well-understood nanoarchitecture construction protocols often rely on the ‘classic’ supramolecular interactions, namely hydrogen bonding and metal-organic coordination. Further examples include rarely encountered special cases where substrate-mediated processes or repulsive forces drive the emergence of order. The demonstrated functionalities include tuning of the electronic structure by confining surface state electrons and atomically defined arrays of magnetic complexes. Moreover, the high-quality templates can be utilized for imposing novel thin film growth modes or act as basic constituents of nanoswitches. Finally, the aptitude of the STM+XS approach for the emerging field of creating nanoarchitectures by on-surface covalent coupling is addressed.

Measurable characteristics of lysozyme crystal growth

NASA Technical Reports Server (NTRS)

Gorti, Sridhar; Forsythe, Elizabeth L.; Pusey, Marc L.

2005-01-01

The behavior of protein crystal growth is estimated from measurements performed at both the microscopic and molecular levels. In the absence of solutal flow, it was determined that a model that balances the macromolecular flux toward the crystal surface with the flux of the crystal surface well characterizes crystal growth observed using microscopic methods. Namely, it was determined that the model provides accurate estimates for the crystal-growth velocities upon evaluation of crystal-growth measurements obtained in time. Growth velocities thus determined as a function of solution supersaturation were further interpreted using established deterministic models. From analyses of crystal-growth velocities, it was found that the mode of crystal growth varies with respect to increasing solution supersaturation, possibly owing to kinetic roughening. To verify further the hypothesis of kinetic roughening, crystal growth at the molecular level was examined using atomic force microscopy (AFM). From the AFM measurements, it was found that the magnitude of surface-height fluctuations, h(x), increases with increasing solution supersaturation. In contrast, the estimated characteristic length, xi, decreases rapidly upon increasing solution supersaturation. It was conjectured that the magnitude of both h(x) and xi could possibly determine the mode of crystal growth. Although the data precede any exact theory, the non-critical divergence of h(x) and xi with respect to increasing solution supersaturation was nevertheless preliminarily established. Moreover, approximate models to account for behavior of both h(x) and xi are also presented.

Analysis of the low molecular weight fraction of serum by LC-dual ESI-FT-ICR mass spectrometry: precision of retention time, mass, and ion abundance.

PubMed

Johnson, Kenneth L; Mason, Christopher J; Muddiman, David C; Eckel, Jeanette E

2004-09-01

This study quantifies the experimental uncertainty for LC retention time, mass measurement precision, and ion abundance obtained from replicate nLC-dual ESI-FT-ICR analyses of the low molecular weight fraction of serum. We used ultrafiltration to enrich the < 10-kDa fraction of components from the high-abundance proteins in a pooled serum sample derived from ovarian cancer patients. The THRASH algorithm for isotope cluster detection was applied to five replicate nLC-dual ESI-FT-ICR chromatograms. A simple two-level grouping algorithm was applied to the more than 7000 isotope clusters found in each replicate and identified 497 molecular species that appeared in at least four of the replicates. In addition, a representative set of 231 isotope clusters, corresponding to 188 unique molecular species, were manually interpreted to verify the automated algorithm and to set its tolerances. For nLC retention time reproducibility, 95% of the 497 species had a 95% confidence interval of the mean of +/- 0.9 min or less without the use of chromatographic alignment procedures. Furthermore, 95% of the 497 species had a mass measurement precision of < or = 3.2 and < or = 6.3 ppm for internally and externally calibrated spectra, respectively. Moreover, 95% of replicate ion abundance measurements, covering an ion abundance range of approximately 3 orders of magnitude, had a coefficient of variation of less than 62% without using any normalization functions. The variability of ion abundance was independent of LC retention time, mass, and ion abundance quartile. These measures of analytical reproducibility establish a statistical rationale for differentiating healthy and disease patient populations for the elucidation of biomarkers in the low molecular fraction of serum. Copyright 2004 American Chemical Society

Better, Cheaper, Faster Molecular Dynamics

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; DeVincenzi, Donald L. (Technical Monitor)

2001-01-01

Recent, revolutionary progress in genomics and structural, molecular and cellular biology has created new opportunities for molecular-level computer simulations of biological systems by providing vast amounts of data that require interpretation. These opportunities are further enhanced by the increasing availability of massively parallel computers. For many problems, the method of choice is classical molecular dynamics (iterative solving of Newton's equations of motion). It focuses on two main objectives. One is to calculate the relative stability of different states of the system. A typical problem that has' such an objective is computer-aided drug design. Another common objective is to describe evolution of the system towards a low energy (possibly the global minimum energy), "native" state. Perhaps the best example of such a problem is protein folding. Both types of problems share the same difficulty. Often, different states of the system are separated by high energy barriers, which implies that transitions between these states are rare events. This, in turn, can greatly impede exploration of phase space. In some instances this can lead to "quasi non-ergodicity", whereby a part of phase space is inaccessible on time scales of the simulation. To overcome this difficulty and to extend molecular dynamics to "biological" time scales (millisecond or longer) new physical formulations and new algorithmic developments are required. To be efficient they should account for natural limitations of multi-processor computer architecture. I will present work along these lines done in my group. In particular, I will focus on a new approach to calculating the free energies (stability) of different states and to overcoming "the curse of rare events". I will also discuss algorithmic improvements to multiple time step methods and to the treatment of slowly decaying, log-ranged, electrostatic effects.

ALMA Multiple-transition Molecular Line Observations of the Ultraluminous Infrared Galaxy IRAS 20551-4250: Different HCN, HCO+, and HNC Excitation, and Implications for Infrared Radiative Pumping

NASA Astrophysics Data System (ADS)

Imanishi, Masatoshi; Nakanishi, Kouichiro; Izumi, Takuma

2017-11-01

We present our ALMA multi-transition molecular line observational results for the ultraluminous infrared galaxy IRAS 20551-4250, which is known to contain a luminous buried active galactic nucleus and shows detectable vibrationally excited (v 2 = 1f) HCN and HNC emission lines. The rotational J = 1-0, 4-3, and 8-7 of HCN, {{HCO}}+, and HNC emission lines were clearly detected at a vibrational ground level (v = 0). Vibrationally excited (v 2 = 1f) J = 4-3 emission lines were detected for HCN and HNC, but not for {{HCO}}+. Their observed flux ratios further support our previously obtained suggestion, based on J = 3-2 data, that (1) infrared radiative pumping plays a role in rotational excitation at v = 0, at least for HCN and HNC, and (2) HCN abundance is higher than {{HCO}}+ and HNC. The flux measurements of the isotopologue H13CN, {{{H}}}13{{CO}}+, and HN13C J = 3-2 emission lines support the higher HCN abundance scenario. Based on modeling with collisional excitation, we constrain the physical properties of these line-emitting molecular gases, but find that higher HNC rotational excitation than HCN and {{HCO}}+ is difficult to explain, due to the higher effective critical density of HNC. We consider the effects of infrared radiative pumping using the available 5-30 μm infrared spectrum and find that our observational results are well-explained if the radiation source is located at 30-100 pc from the molecular gas. The simultaneously covered very bright CO J = 3-2 emission line displays a broad emission wing, which we interpret as being due to molecular outflow activity with the estimated rate of ˜ 150 {M}⊙ {{yr}}-1.

[Identification of mycobacteria to the species level by molecular methods in the Public Health Laboratory of Bogotá, Colombia].

PubMed

Hernández-Toloza, Johana Esther; Rincón-Serrano, María de Pilar; Celis-Bustos, Yamile Adriana; Aguillón, Claudia Inés

2016-01-01

Global epidemiology of non-tuberculous mycobacteria (NTM) is unknown due to the fact that notification is not required in many countries, however the number of infection reports and outbreaks caused by NTM suggest a significant increase in the last years. Traditionally, mycobacteria identification is made through biochemical profiles which allow to differentiate M. tuberculosis from NTM, and in some cases the mycobacteria species. Nevertheless, these methods are technically cumbersome and time consuming. On the other hand, the introduction of methods based on molecular biology has improved the laboratory diagnosis of NTM. To establish the NTM frequency in positive cultures for acid-fast bacilli (AAFB) which were sent to Laboratorio de Salud Pública de Bogotá over a 12 month period. A total of 100 positive cultures for acid-fast bacilli from public and private hospitals from Bogotá were identified by both biochemical methods and the molecular methods PRA (PCR-restriction enzyme analysis) and multiplex-PCR. Furthermore, low prevalence mycobacteria species and non-interpretable results were confirmed by 16SrDNA sequentiation analysis. Identification using the PRA method showed NMT occurrence in 11% of cultures. In addition, this molecular methodology allowed to detect the occurrence of more than one mycobacteria in 4% of the cultures. Interestingly, a new M. kubicae pattern of PCR-restriction analysis is reported in our study. Using a mycobacteria identification algorithm, which includes the molecular method PRA, improves the diagnostic power of conventional methods and could help to advance both NTM epidemiology knowledge and mycobacteriosis control. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The effect of glycosylation on the transferrin structure: A molecular dynamic simulation analysis.

PubMed

Ghanbari, Z; Housaindokht, M R; Bozorgmehr, M R; Izadyar, M

2016-09-07

Transferrins have been defined by the highly cooperative binding of iron and a carbonate anion to form a Fe-CO3-Tf ternary complex. As such, the layout of the binding site residues affects transferrin function significantly; In contrast to N-lobe, C-lobe binding site of the transferrin structure has been less characterized and little research which surveyed the interaction of carbonate with transferrin in the C-lobe binding site has been found. In the present work, molecular dynamic simulation was employed to gain access into the molecular level understanding of carbonate binding site and their interactions in each lobe. Residues responsible for carbonate binding of transferrin structure were pointed out. In addition, native human transferrin is a glycoprotein that two N-linked complex glycan chains located in the C-lobe. Usually, in the molecular dynamic simulation for simplifying, glycan is removed from the protein structure. Here, we explore the effect of glycosylation on the transferrin structure. Glycosylation appears to have an effect on the layout of the binding site residue and transferrin structure. On the other hand, sometimes the entire transferrin formed by separated lobes that it allows the results to be interpreted in a straightforward manner rather than more parameters required for full length protein. But, it should be noted that there are differences between the separated lobe and full length transferrin, hence, a comparative analysis by the molecular dynamic simulation was performed to investigate such structural variations. Results revealed that separation in C-lobe caused a significant structural variation in comparison to N-lobe. Consequently, the separated lobes and the full length one are different, showing the importance of the interlobe communication and the impact of the lobes on each other in the transferrin structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Historeceptomic Fingerprints for Drug-Like Compounds.

PubMed

Shmelkov, Evgeny; Grigoryan, Arsen; Swetnam, James; Xin, Junyang; Tivon, Doreen; Shmelkov, Sergey V; Cardozo, Timothy

2015-01-01

Most drugs exert their beneficial and adverse effects through their combined action on several different molecular targets (polypharmacology). The true molecular fingerprint of the direct action of a drug has two components: the ensemble of all the receptors upon which a drug acts and their level of expression in organs/tissues. Conversely, the fingerprint of the adverse effects of a drug may derive from its action in bystander tissues. The ensemble of targets is almost always only partially known. Here we describe an approach improving upon and integrating both components: in silico identification of a more comprehensive ensemble of targets for any drug weighted by the expression of those receptors in relevant tissues. Our system combines more than 300,000 experimentally determined bioactivity values from the ChEMBL database and 4.2 billion molecular docking scores. We integrated these scores with gene expression data for human receptors across a panel of human tissues to produce drug-specific tissue-receptor (historeceptomics) scores. A statistical model was designed to identify significant scores, which define an improved fingerprint representing the unique activity of any drug. These multi-dimensional historeceptomic fingerprints describe, in a novel, intuitive, and easy to interpret style, the holistic, in vivo picture of the mechanism of any drug's action. Valuable applications in drug discovery and personalized medicine, including the identification of molecular signatures for drugs with polypharmacologic modes of action, detection of tissue-specific adverse effects of drugs, matching molecular signatures of a disease to drugs, target identification for bioactive compounds with unknown receptors, and hypothesis generation for drug/compound phenotypes may be enabled by this approach. The system has been deployed at drugable.org for access through a user-friendly web site.

The new WHO 2016 classification of brain tumors-what neurosurgeons need to know.

PubMed

Banan, Rouzbeh; Hartmann, Christian

2017-03-01

The understanding of molecular alterations of tumors has severely changed the concept of classification in all fields of pathology. The availability of high-throughput technologies such as next-generation sequencing allows for a much more precise definition of tumor entities. Also in the field of brain tumors a dramatic increase of knowledge has occurred over the last years partially calling into question the purely morphologically based concepts that were used as exclusive defining criteria in the WHO 2007 classification. Review of the WHO 2016 classification of brain tumors as well as a search and review of publications in the literature relevant for brain tumor classification from 2007 up to now. The idea of incorporating the molecular features in classifying tumors of the central nervous system led the authors of the new WHO 2016 classification to encounter inevitable conceptual problems, particularly with respect to linking morphology to molecular alterations. As a solution they introduced the concept of a "layered diagnosis" to the classification of brain tumors that still allows at a lower level a purely morphologically based diagnosis while partially forcing the incorporation of molecular characteristics for an "integrated diagnosis" at the highest diagnostic level. In this context the broad availability of molecular assays was debated. On the one hand molecular antibodies specifically targeting mutated proteins should be available in nearly all neuropathological laboratories. On the other hand, different high-throughput assays are accessible only in few first-world neuropathological institutions. As examples oligodendrogliomas are now primarily defined by molecular characteristics since the required assays are generally established, whereas molecular grouping of ependymomas, found to clearly outperform morphologically based tumor interpretation, was rejected from inclusion in the WHO 2016 classification because the required assays are currently only established in a small number of institutions. In summary, while neuropathologists have now encountered various challenges in the transitional phase from the previous WHO 2007 version to the new WHO 2016 classification of brain tumors, clinical neurooncologists now face many new diagnoses allowing a clearly improved understanding that could offer them more effective therapeutic opportunities in neurooncological treatment. The new WHO 2016 classification presumably presents the highest number of modifications since the initial WHO classification of 1979 and thereby forces all professionals in the field of neurooncology to intensively understand the new concepts. This review article aims to present the basic concepts of the new WHO 2016 brain tumor classification for neurosurgeons with a focus on neurooncology.

Analyzing milestoning networks for molecular kinetics: definitions, algorithms, and examples.

PubMed

Viswanath, Shruthi; Kreuzer, Steven M; Cardenas, Alfredo E; Elber, Ron

2013-11-07

Network representations are becoming increasingly popular for analyzing kinetic data from techniques like Milestoning, Markov State Models, and Transition Path Theory. Mapping continuous phase space trajectories into a relatively small number of discrete states helps in visualization of the data and in dissecting complex dynamics to concrete mechanisms. However, not only are molecular networks derived from molecular dynamics simulations growing in number, they are also getting increasingly complex, owing partly to the growth in computer power that allows us to generate longer and better converged trajectories. The increased complexity of the networks makes simple interpretation and qualitative insight of the molecular systems more difficult to achieve. In this paper, we focus on various network representations of kinetic data and algorithms to identify important edges and pathways in these networks. The kinetic data can be local and partial (such as the value of rate coefficients between states) or an exact solution to kinetic equations for the entire system (such as the stationary flux between vertices). In particular, we focus on the Milestoning method that provides fluxes as the main output. We proposed Global Maximum Weight Pathways as a useful tool for analyzing molecular mechanism in Milestoning networks. A closely related definition was made in the context of Transition Path Theory. We consider three algorithms to find Global Maximum Weight Pathways: Recursive Dijkstra's, Edge-Elimination, and Edge-List Bisection. The asymptotic efficiency of the algorithms is analyzed and numerical tests on finite networks show that Edge-List Bisection and Recursive Dijkstra's algorithms are most efficient for sparse and dense networks, respectively. Pathways are illustrated for two examples: helix unfolding and membrane permeation. Finally, we illustrate that networks based on local kinetic information can lead to incorrect interpretation of molecular mechanisms.

Mass spectrometry based lipid(ome) analyzer and molecular platform: a new software to interpret and analyze electrospray and/or matrix-assisted laser desorption/ionization mass spectrometric data of lipids: a case study from Mycobacterium tuberculosis.

PubMed

Sabareesh, Varatharajan; Singh, Gurpreet

2013-04-01

Mass Spectrometry based Lipid(ome) Analyzer and Molecular Platform (MS-LAMP) is a new software capable of aiding in interpreting electrospray ionization (ESI) and/or matrix-assisted laser desorption/ionization (MALDI) mass spectrometric data of lipids. The graphical user interface (GUI) of this standalone programme is built using Perl::Tk. Two databases have been developed and constituted within MS-LAMP, on the basis of Mycobacterium tuberculosis (M. tb) lipid database (www.mrl.colostate.edu) and that of Lipid Metabolites and Pathways Strategy Consortium (LIPID MAPS; www.lipidmaps.org). Different types of queries entered through GUI would interrogate with a chosen database. The queries can be molecular mass(es) or mass-to-charge (m/z) value(s) and molecular formula. LIPID MAPS identifier also can be used to search but not for M. tb lipids. Multiple choices have been provided to select diverse ion types and lipids. Satisfying to input parameters, a glimpse of various lipid categories and their population distribution can be viewed in the output. Additionally, molecular structures of lipids in the output can be seen using ChemSketch (www.acdlabs.com), which has been linked to the programme. Furthermore, a version of MS-LAMP for use in Linux operating system is separately available, wherein PyMOL can be used to view molecular structures that result as output from General Lipidome MS-LAMP. The utility of this software is demonstrated using ESI mass spectrometric data of lipid extracts of M. tb grown under two different pH (5.5 and 7.0) conditions. Copyright © 2013 John Wiley & Sons, Ltd.

Distance geometry protocol to generate conformations of natural products to structurally interpret ion mobility-mass spectrometry collision cross sections.

PubMed

Stow, Sarah M; Goodwin, Cody R; Kliman, Michal; Bachmann, Brian O; McLean, John A; Lybrand, Terry P

2014-12-04

Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data.

Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections

PubMed Central

2015-01-01

Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data. PMID:25360896

Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs

PubMed Central

Seifert, Marva; Garfein, Richard S.; Rodwell, Timothy C.

2017-01-01

ABSTRACT Rapid molecular diagnostics have great potential to limit the spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis genome that confer phenotypic drug resistance. However, there have been few data published regarding the relationships between the detected M. tuberculosis resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological, and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between M. tuberculosis resistance mutations and patient mortality. The presence of an rrs 1401G mutation was associated with significantly higher odds of patient mortality (adjusted odds ratio [OR] = 5.72; 95% confidence interval [CI], 1.65 to 19.84]) after adjusting for relevant patient clinical characteristics and all other resistance mutations. Further analysis of mutations, categorized by the associated resistance level, indicated that the detection of mutations associated with high-level fluoroquinolone (OR, 3.99 [95% CI, 1.10 to 14.40]) and kanamycin (OR, 5.47 [95% CI, 1.64 to 18.24]) resistance was also significantly associated with higher odds of patient mortality, even after accounting for clinical site, patient age, reported smoking history, body mass index (BMI), diabetes, HIV, and all other resistance mutations. Specific gyrA and rrs resistance mutations, associated with high-level resistance, were associated with patient mortality as identified in clinical M. tuberculosis isolates from a diverse M/XDR-TB patient population at three high-burden clinical sites. These results have important implications for the interpretation of molecular diagnostics, including identifying patients at increased risk for mortality during treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT02170441.) PMID:28404672

Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs.

PubMed

Georghiou, Sophia B; Seifert, Marva; Catanzaro, Donald G; Garfein, Richard S; Rodwell, Timothy C

2017-06-01

Rapid molecular diagnostics have great potential to limit the spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis genome that confer phenotypic drug resistance. However, there have been few data published regarding the relationships between the detected M. tuberculosis resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological, and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between M. tuberculosis resistance mutations and patient mortality. The presence of an rrs 1401G mutation was associated with significantly higher odds of patient mortality (adjusted odds ratio [OR] = 5.72; 95% confidence interval [CI], 1.65 to 19.84]) after adjusting for relevant patient clinical characteristics and all other resistance mutations. Further analysis of mutations, categorized by the associated resistance level, indicated that the detection of mutations associated with high-level fluoroquinolone (OR, 3.99 [95% CI, 1.10 to 14.40]) and kanamycin (OR, 5.47 [95% CI, 1.64 to 18.24]) resistance was also significantly associated with higher odds of patient mortality, even after accounting for clinical site, patient age, reported smoking history, body mass index (BMI), diabetes, HIV, and all other resistance mutations. Specific gyrA and rrs resistance mutations, associated with high-level resistance, were associated with patient mortality as identified in clinical M. tuberculosis isolates from a diverse M/XDR-TB patient population at three high-burden clinical sites. These results have important implications for the interpretation of molecular diagnostics, including identifying patients at increased risk for mortality during treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT02170441.). Copyright © 2017 American Society for Microbiology.

Causality in cancer research: a journey through models in molecular epidemiology and their philosophical interpretation.

PubMed

Vineis, Paolo; Illari, Phyllis; Russo, Federica

2017-01-01

In the last decades, Systems Biology (including cancer research) has been driven by technology, statistical modelling and bioinformatics. In this paper we try to bring biological and philosophical thinking back. We thus aim at making different traditions of thought compatible: (a) causality in epidemiology and in philosophical theorizing-notably, the "sufficient-component-cause framework" and the "mark transmission" approach; (b) new acquisitions about disease pathogenesis, e.g. the "branched model" in cancer, and the role of biomarkers in this process; (c) the burgeoning of omics research, with a large number of "signals" and of associations that need to be interpreted. In the paper we summarize first the current views on carcinogenesis, and then explore the relevance of current philosophical interpretations of "cancer causes". We try to offer a unifying framework to incorporate biomarkers and omic data into causal models, referring to a position called "evidential pluralism". According to this view, causal reasoning is based on both "evidence of difference-making" (e.g. associations) and on "evidence of underlying biological mechanisms". We conceptualize the way scientists detect and trace signals in terms of information transmission , which is a generalization of the mark transmission theory developed by philosopher Wesley Salmon. Our approach is capable of helping us conceptualize how heterogeneous factors such as micro and macro-biological and psycho-social-are causally linked. This is important not only to understand cancer etiology, but also to design public health policies that target the right causal factors at the macro-level.

The Relevance of External Quality Assessment for Molecular Testing for ALK Positive Non-Small Cell Lung Cancer: Results from Two Pilot Rounds Show Room for Optimization

PubMed Central

Tembuyser, Lien; Tack, Véronique; Zwaenepoel, Karen; Pauwels, Patrick; Miller, Keith; Bubendorf, Lukas; Kerr, Keith; Schuuring, Ed; Thunnissen, Erik; Dequeker, Elisabeth M. C.

2014-01-01

Background and Purpose Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is a critical biomarker to predict response to tyrosine kinase inhibitors such as crizotinib. To promote high quality testing in non-small cell lung cancer, the European Society of Pathology has introduced an external quality assessment scheme. This article summarizes the results of the first two pilot rounds organized in 2012–2013. Materials and Methods Tissue microarray slides consisting of cell-lines and resection specimens were distributed with the request for routine ALK testing using IHC or FISH. Participation in ALK FISH testing included the interpretation of four digital FISH images. Results Data from 173 different laboratories was obtained. Results demonstrate decreased error rates in the second round for both ALK FISH and ALK IHC, although the error rates were still high and the need for external quality assessment in laboratories performing ALK testing is evident. Error rates obtained by FISH were lower than by IHC. The lowest error rates were observed for the interpretation of digital FISH images. Conclusion There was a large variety in FISH enumeration practices. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing. PMID:25386659

The relevance of external quality assessment for molecular testing for ALK positive non-small cell lung cancer: results from two pilot rounds show room for optimization.

PubMed

Tembuyser, Lien; Tack, Véronique; Zwaenepoel, Karen; Pauwels, Patrick; Miller, Keith; Bubendorf, Lukas; Kerr, Keith; Schuuring, Ed; Thunnissen, Erik; Dequeker, Elisabeth M C

2014-01-01

Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is a critical biomarker to predict response to tyrosine kinase inhibitors such as crizotinib. To promote high quality testing in non-small cell lung cancer, the European Society of Pathology has introduced an external quality assessment scheme. This article summarizes the results of the first two pilot rounds organized in 2012-2013. Tissue microarray slides consisting of cell-lines and resection specimens were distributed with the request for routine ALK testing using IHC or FISH. Participation in ALK FISH testing included the interpretation of four digital FISH images. Data from 173 different laboratories was obtained. Results demonstrate decreased error rates in the second round for both ALK FISH and ALK IHC, although the error rates were still high and the need for external quality assessment in laboratories performing ALK testing is evident. Error rates obtained by FISH were lower than by IHC. The lowest error rates were observed for the interpretation of digital FISH images. There was a large variety in FISH enumeration practices. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing.

New Material of Beelzebufo, a Hyperossified Frog (Amphibia: Anura) from the Late Cretaceous of Madagascar

PubMed Central

Evans, Susan E.; Groenke, Joseph R.; Jones, Marc E. H.; Turner, Alan H.; Krause, David W.

2014-01-01

The extant anuran fauna of Madagascar is exceptionally rich and almost completely endemic. In recent years, many new species have been described and understanding of the history and relationships of this fauna has been greatly advanced by molecular studies, but very little is known of the fossil history of frogs on the island. Beelzebufo ampinga, the first named pre-Holocene frog from Madagascar, was described in 2008 on the basis of numerous disarticulated cranial and postcranial elements from the Upper Cretaceous (Maastrichtian) Maevarano Formation of Madagascar. These specimens documented the presence of a hyperossified taxon that differed strikingly from extant Malagasy frogs in its large size and heavy coarse cranial exostosis. Here we describe and analyse new, articulated, and more complete material of the skull, vertebral column, and hind limb, as well as additional isolated elements discovered since 2008. μCT scans allow a detailed understanding of both internal and external morphology and permit a more accurate reconstruction. The new material shows Beelzebufo to have been even more bizarre than originally interpreted, with large posterolateral skull flanges and sculptured vertebral spine tables. The apparent absence of a tympanic membrane, the strong cranial exostosis, and vertebral morphology suggest it may have burrowed during seasonally arid conditions, which have been interpreted for the Maevarano Formation from independent sedimentological and taphonomic evidence. New phylogenetic analyses, incorporating both morphological and molecular data, continue to place Beelzebufo with hyloid rather than ranoid frogs. Within Hyloidea, Beelzebufo still groups with the South American Ceratophryidae thus continuing to pose difficulties with both biogeographic interpretations and prior molecular divergence dates. PMID:24489877

Structural and vibrational study of 2-MethoxyEthylAmmonium Nitrate (2-OMeEAN): Interpretation of experimental results with ab initio molecular dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campetella, M.; Caminiti, R.; Bencivenni, L.

2016-07-14

In this work we report an analysis of the bulk phase of 2-methoxyethylammonium nitrate based on ab initio molecular dynamics. The structural and dynamical features of the ionic liquid have been characterized and the computational findings have been compared with the experimental X-ray diffraction patterns, with infrared spectroscopy data, and with the results obtained from molecular dynamics simulations. The experimental infrared spectrum was interpreted with the support of calculated vibrational density of states as well as harmonic frequency calculations of selected gas phase clusters. Particular attention was addressed to the high frequency region of the cation (ω > 2000 cm{supmore » −1}), where the vibrational motions involve the NH{sub 3}+ group responsible for hydrogen bond formation, and to the frequency range 1200-1400 cm{sup −1} where the antisymmetric stretching mode (ν{sub 3}) of nitrate is found. Its multiple absorption lines in the liquid arise from the removal of the degeneracy present in the D{sub 3h} symmetry of the isolated ion. Our ab initio molecular dynamics leads to a rationalization of the frequency shifts and splittings, which are inextricably related to the structural modifications induced by a hydrogen bonding environment. The DFT calculations lead to an inhomogeneous environment.« less

Normal and abnormal development of the kidney: a clinician's interpretation of current knowledge.

PubMed

Glassberg, Kenneth I

2002-06-01

The recent basic science literature is replete with new discoveries in the molecular genetics of renal development. However, little of this information has filtered into urological textbooks and journals. An effort is made herein to integrate these new findings and propose a more sophisticated blueprint of renal development than the one traditionally taught in medical school and residency. To accomplish this goal the author offers simple definitions and interpretations of complicated terms and events, and points out how maldevelopment results when mutations take place. A review of recent advances in the molecular genetics of renal development and maldevelopment was done. Renal metanephric development results from the expression of many genes in the ureteral bud and metanephric blastema with each sending messages to the other to induce organogenesis. Currently an understanding of normal renal organogenesis stems from a study of disease states resulting from perturbations in molecular genetics. In turn, a better understanding of normal renal organogenesis facilitates an understanding of how dysplasia, hypoplasia, cystic disease and tumors develop when molecular genetics go awry. For each form of renal dysgenesis and for most renal tumors 1 or more gene defects are eventually identified. The young urologist based in these new discoveries would be better prepared to make the breakthroughs in the future that are necessary for advancing the prevention and management of these conditions.

Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

PubMed

Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

2016-09-09

Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators, biological pathways, and gene networks.

The relation between social anxiety and biased interpretations in adolescents with mild intellectual disabilities.

PubMed

Houtkamp, Esther O; van der Molen, Mariët J; de Voogd, E Leone; Salemink, Elske; Klein, Anke M

2017-08-01

Cognitive theories of anxiety emphasize the importance of cognitive processes in the onset and maintenance of anxiety disorders. However, little is known about these processes in children and adolescents with Mild Intellectual Disabilities (MID). The aim of this study was to investigate interpretation bias and its content-specificity in adolescents with MID who varied in their levels of social anxiety. In total, 631 adolescents from seven special secondary schools for MID filled in questionnaires to measure their levels of social anxiety. They also completed the Interpretation Recognition Task to measure how they interpret ambiguous situations. Adolescents with higher self-reported levels of social anxiety interpreted ambiguous scenarios as more negative than adolescents with lower self-reported social anxiety. Furthermore, this negative interpretation was specific for social situations; social anxiety was only associated with ambiguous social anxiety-related scenarios, but not with other anxiety-related scenarios. These findings support the hypothesis that socially anxious adolescents with MID display an interpretation bias that is specific for stimuli that are relevant for their own anxiety. This insight is useful for improving treatments for anxious adolescents with MID by targeting content-specific interpretation biases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does body mass play a role in the regulation of food intake?

PubMed

Speakman, John R; Stubbs, R James; Mercer, Julian G

2002-11-01

It is widely believed that body fatness (and hence total body mass) is regulated by a lipostatic feedback system. This system is suggested to involve at least one peripheral signalling compound, which signals to the brain the current size of body fat stores. In the brain the level of the signal is compared with a desirable target level, and food intake and energy expenditure are then regulated to effect changes in the size of body fat stores. There is considerable support for this theory at several different levels of investigation. Patterns of body-mass change in subjects forced into energy imbalance seem to demonstrate homeostasis, and long-term changes in body mass are minor compared with the potential changes that might result from energy imbalance. Molecular studies of signalling compounds have suggested a putative lipostatic signal (leptin) and a complex network of downstream processing events in the brain, polymorphisms of which lead to disruption of body-mass regulation. This network of neuropeptides provides a rich seam of potential pharmaceutical targets for the control of obesity. Despite this consistent explanation for the observed phenomena at several different levels of enquiry, there are alternative explanations. In the present paper we explore the possibility that the existence of lipostatic regulation of body fatness is an illusion generated by the links between body mass and energy expenditure and responses to energy imbalance that are independent of body mass. Using computer-based models of temporal patterns in energy balance we show that common patterns of change in body mass following perturbation can be adequately explained by this 'non-lipostatic' model. This model has some important implications for the interpretations that we place on the molecular events in the brain, and ultimately in the search for pharmaceutical agents for alleviation of obesity.

Collisional excitation of sulfur dioxide by molecular hydrogen in warm molecular clouds

NASA Astrophysics Data System (ADS)

Balança, Christian; Spielfiedel, Annie; Feautrier, Nicole

2016-08-01

Interpretation of SO2 line emission in warm environments requires a detailed knowledge of collisional rate coefficients for a wide range of levels and temperatures. Using an accurate theoretical interaction potential for SO2-H2, rate coefficients for collisions of SO2 with para and ortho-H2 for the 31 first SO2, rotational levels are calculated for temperatures up to 500 K using the coupled states (CS) approximation. From a comparison with previously published close-coupling (CC) results, it was shown that the two sets of data agree within 20-30 per cent for both para- and ortho-H2 collisions. As previously found within the CC approach, the CS rate coefficients with ortho and para-H2 differ by a factor of 2 in average, the largest being mainly the rates for collisions with ortho-H2. For higher levels and temperatures, rate constants were computed within the infinite order sudden (IOS) approximation. Rate coefficients were obtained for the lowest 410 rotational levels of SO2 in the 100-1000 K temperature range. A comparison at 30, 100 and 300 K of the IOS data with the corresponding para-H2 CS results indicates that the IOS approximation systematically underestimates the CS results by a factor up to 2 at the lowest temperatures. As expected, IOS and CS rates are in a better agreement at higher temperatures. Considering that the IOS theory was developed for collisions with para-H2, this approach cannot describe with the same accuracy collisions with ortho-H2. So, our IOS data may be considered as quite reliable for collisions with para-H2 and less accurate for collisions with ortho-H2.

Molecular Population Genetic Structure in the Piping Plover

USGS Publications Warehouse

Miller, Mark P.; Haig, Susan M.; Gratto-Trevor, Cheri L.; Mullins, Thomas D.

2009-01-01

The Piping Plover (Charadrius melodus) is a migratory shorebird currently listed as Endangered in Canada and the U.S. Great Lakes, and threatened throughout the remainder of its U.S. breeding and winter range. In this study, we undertook the first comprehensive molecular genetic-based investigation of Piping Plovers. Our primary goals were to (1) address higher level subspecific taxonomic issues, (2) characterize population genetic structure, and (3) make inferences regarding past bottlenecks or population expansions that have occurred within this species. Our analyses included samples of individuals from 23 U.S. States and Canadian Provinces, and were based on mitochondrial DNA sequences (580 bp, n = 245 individuals) and eight nuclear microsatellite loci (n = 229 individuals). Our findings illustrate strong support for separate Atlantic and Interior Piping Plover subspecies (C. m. melodus and C. m. circumcinctus, respectively). Birds from the Great Lakes region were allied with the Interior subspecies group and should be taxonomically referred to as C. m. circumcinctus. Population genetic analyses suggested that genetic structure was stronger among Atlantic birds relative to the Interior group. This pattern indicates that natal and breeding site fidelity may be reduced among Interior birds. Furthermore, analyses suggested that Interior birds have previously experienced genetic bottlenecks, whereas no evidence for such patterns existed among the Atlantic subspecies. Likewise, genetic analyses indicated that the Great Lakes region has experienced a population expansion. This finding may be interpreted as population growth following a previous bottleneck event. No genetic evidence for population expansions was found for Atlantic, Prairie Canada, or U.S. Northern Great Plains individuals. We interpret our population history insights in light of 25 years of Piping Plover census data. Overall, differences observed between Interior and Atlantic birds may reflect differences in spatiotemporal stability of Piping Plover nesting habitat between regions.

The Anatomy of the Young Protostellar Outflow HH 211: Strong Evidence for CO v = 1-0 Fundamental Band Emission from Dense Gas in the Terminal Shock

NASA Astrophysics Data System (ADS)

Tappe, Achim; Forbrich, J.; Martín, S.; Lada, C. J.

2011-05-01

We present Spitzer Space Telescope 5-37 µm spectroscopic mapping observations toward the southeastern lobe of the young protostellar outflow HH 211 (part of IC 348 in Perseus, 260 pc). The terminal shock of the outflow shows a rich atomic and molecular spectrum with emission lines from OH, H2O, HCO+, CO2, H2, HD, [Fe II], [Si II], [Ne II], [S I], and [Cl I]. The spectrum also shows a rising continuum towards 5 µm, which we interpret as unresolved emission lines from highly excited rotational levels of the CO v=1-0 fundamental band. This interpretation is confirmed by a strong excess flux observed in the Spitzer IRAC 4-5 µm channel 2 image. We also observed the terminal outflow shock of this lobe with the Submillimeter Array (SMA) and detected pure rotational emission from CO 2-1, HCO+ 3-2, and HCN 3-2. The rotationally excited CO traces the collimated outflow and the terminal shock, whereas the vibrationally excited CO seen with Spitzer follows the continuation of the collimated outflow backbone in the terminal shock. The extremely high critical densities of the CO v=1-0 rovibrational lines indicate terminal shock jet densities larger than 107 cm-3. The unique combination of mid-infrared, submillimeter, and previous near-infrared observations allow us to gain detailed insights into the interaction of one of the youngest known protostellar outflows with its surrounding molecular cloud. Our results help to understand the nature of some of the so-called `green fuzzies’ (Extended Green Objects) identified by their Spitzer IRAC channel 2 excess and association with star-forming regions. They also provide a critical observational test to models of pulsed protostellar jets.

Novel Interpretation of Molecular Diagnosis of Congenital Toxoplasmosis According to Gestational Age at the Time of Maternal Infection

PubMed Central

Sterkers, Yvon; Pratlong, Francine; Albaba, Sahar; Loubersac, Julie; Picot, Marie-Christine; Pretet, Vanessa; Issert, Eric; Boulot, Pierre

2012-01-01

From a prospective cohort of 344 women who seroconverted for toxoplasmosis during pregnancy, 344 amniotic fluid, 264 placenta, and 216 cord blood samples were tested for diagnosis of congenital toxoplasmosis using the same PCR assay. The sensitivity and negative predictive value of the PCR assay using amniotic fluid were 86.3% and 97.2%, respectively, and both specificity and positive predictive value were 100%. Using placenta and cord blood, sensitivities were 79.5% and 21.2%, and specificities were 92% and 100%, respectively. In addition, the calculation of pretest and posttest probabilities and the use of logistic regression allowed us to obtain curves that give a dynamic interpretation of the risk of congenital toxoplasmosis according to gestational age at maternal infection, as represented by the three sample types (amniotic fluid, placenta, and cord blood). Two examples are cited here: for a maternal infection at 25 weeks of amenorrhea, a negative result of prenatal diagnosis allowed estimation of the probability of congenital toxoplasmosis at 5% instead of an a priori (pretest) risk estimate of 33%. For an infection at 10 weeks of amenorrhea associated with a pretest congenital toxoplasmosis risk of 7%, a positive PCR result using placenta at birth yields a risk increase to 43%, while a negative result damps down the risk to 0.02%. Thus, with a molecular diagnosis performing at a high level, and in spite of the persistence of false negatives, posttest risk curves using both negative and positive results prove highly informative, allowing a better assessment of the actual risk of congenital toxoplasmosis and finally an improved decision guide to treatment. PMID:23035201

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Analysis of sulfates on low molecular weight heparin using mass spectrometry: structural characterization of enoxaparin.

PubMed

Gupta, Rohitesh; Ponnusamy, Moorthy P

2018-05-31

Structural characterization of low molecular weight heparin (LMWH) is critical to meet biosimilarity standards. In this context, the review focuses on structural analysis of labile sulfates attached to the side-groups of LMWH using mass spectrometry. A comprehensive review of this topic will help readers to identify key strategies for tackling the problem related to sulfate loss. At the same time, various mass spectrometry techniques are presented to facilitate compositional analysis of LMWH, mainly enoxaparin. Areas covered: This review summarizes findings on mass spectrometry application for LMWH, including modulation of sulfates, using enzymology and sample preparation approaches. Furthermore, popular open-source software packages for automated spectral data interpretation are also discussed. Successful use of LC/MS can decipher structural composition for LMWH and help evaluate their sameness or biosimilarity with the innovator molecule. Overall, the literature has been searched using PubMed by typing various search queries such as 'enoxaparin', 'mass spectrometry', 'low molecular weight heparin', 'structural characterization', etc. Expert commentary: This section highlights clinically relevant areas that need improvement to achieve satisfactory commercialization of LMWHs. It also primarily emphasizes the advancements in instrumentation related to mass spectrometry, and discusses building automated software for data interpretation and analysis.

Analysing and Rationalising Molecular and Materials Databases Using Machine-Learning

NASA Astrophysics Data System (ADS)

de, Sandip; Ceriotti, Michele

Computational materials design promises to greatly accelerate the process of discovering new or more performant materials. Several collaborative efforts are contributing to this goal by building databases of structures, containing between thousands and millions of distinct hypothetical compounds, whose properties are computed by high-throughput electronic-structure calculations. The complexity and sheer amount of information has made manual exploration, interpretation and maintenance of these databases a formidable challenge, making it necessary to resort to automatic analysis tools. Here we will demonstrate how, starting from a measure of (dis)similarity between database items built from a combination of local environment descriptors, it is possible to apply hierarchical clustering algorithms, as well as dimensionality reduction methods such as sketchmap, to analyse, classify and interpret trends in molecular and materials databases, as well as to detect inconsistencies and errors. Thanks to the agnostic and flexible nature of the underlying metric, we will show how our framework can be applied transparently to different kinds of systems ranging from organic molecules and oligopeptides to inorganic crystal structures as well as molecular crystals. Funded by National Center for Computational Design and Discovery of Novel Materials (MARVEL) and Swiss National Science Foundation.

Apoptosis: a four-week laboratory investigation for advanced molecular and cellular biology students.

PubMed

DiBartolomeis, Susan M; Moné, James P

2003-01-01

Over the past decade, apoptosis has emerged as an important field of study central to ongoing research in many diverse fields, from developmental biology to cancer research. Apoptosis proceeds by a highly coordinated series of events that includes enzyme activation, DNA fragmentation, and alterations in plasma membrane permeability. The detection of each of these phenotypic changes is accessible to advanced undergraduate cell and molecular biology students. We describe a 4-week laboratory sequence that integrates cell culture, fluorescence microscopy, DNA isolation and analysis, and western blotting (immunoblotting) to follow apoptosis in cultured human cells. Students working in teams chemically induce apoptosis, and harvest, process, and analyze cells, using their data to determine the order of events during apoptosis. We, as instructors, expose the students to an environment closely simulating what they would encounter in an active cell or molecular biology research laboratory by having students coordinate and perform multiple tasks simultaneously and by having them experience experimental design using current literature, data interpretation, and analysis to answer a single question. Students are assessed by examination of laboratory notebooks for completeness of experimental protocols and analysis of results and for completion of an assignment that includes questions pertaining to data interpretation and apoptosis.

Structure and vibrational spectra of melaminium bis(trifluoroacetate) trihydrate: FT-IR, FT-Raman and quantum chemical calculations.

PubMed

Sangeetha, V; Govindarajan, M; Kanagathara, N; Marchewka, M K; Gunasekaran, S; Anbalagan, G

2014-05-05

Melaminium bis(trifluoroacetate) trihydrate (MTFA), an organic material has been synthesized and single crystals of MTFA have been grown by the slow solvent evaporation method at room temperature. X-ray powder diffraction analysis confirms that MTFA crystal belongs to the monoclinic system with space group P2/c. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on density functional theory (DFT) B3LYP method with 6-311G(d,p) and 6-311++G(d,p) basis sets. The X-ray diffraction data have been compared with the data of optimized molecular structure. The theoretical results show that the crystal structure can be reproduced by optimized geometry and the vibrational frequencies show good agreement with the experimental values. The nuclear magnetic resonance (NMR) chemical shift of the molecule has been calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. HOMO-LUMO, and other related molecular and electronic properties are calculated. The Mulliken and NBO charges have also been calculated and interpreted. Copyright © 2014 Elsevier B.V. All rights reserved.

Water reorientation in the hydration shells of hydrophilic and hydrophobic solutes

NASA Astrophysics Data System (ADS)

Laage, Damien; Stirnemann, Guillaume; Hynes, James T.

2010-06-01

We discuss some key aspects of our recent theoretical work on water reorientation dynamics, which is important in a wide range of phenomena, including aqueous phase chemical reactions, protein folding, and drug binding to proteins and DNA. It is shown that, contrary to the standard conception that these dynamics are diffusional, the reorientation of a water molecule occurs by sudden, large amplitude angular jumps. The mechanism involves the exchange of one hydrogen bond for another by the reorienting water, and the process can be fruitfully viewed as a chemical reaction. The results for reorientation times, which can be well described analytically, are discussed in the context of the molecular level interpretation of recent ultrafast infrared spectroscopic results, focusing on the concepts of structure making/breaking and solvent ‘icebergs’.

Lophotrochozoan mitochondrial genomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valles, Yvonne; Boore, Jeffrey L.

2005-10-01

Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animalsmore » across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.« less

Grain size distribution in sheared polycrystals

NASA Astrophysics Data System (ADS)

Sarkar, Tanmoy; Biswas, Santidan; Chaudhuri, Pinaki; Sain, Anirban

2017-12-01

Plastic deformation in solids induced by external stresses is of both fundamental and practical interest. Using both phase field crystal modeling and molecular dynamics simulations, we study the shear response of monocomponent polycrystalline solids. We subject mesocale polycrystalline samples to constant strain rates in a planar Couette flow geometry for studying its plastic flow, in particular its grain deformation dynamics. As opposed to equilibrium solids where grain dynamics is mainly driven by thermal diffusion, external stress/strain induce a much higher level of grain deformation activity in the form of grain rotation, coalescence, and breakage, mediated by dislocations. Despite this, the grain size distribution of this driven system shows only a weak power-law correction to its equilibrium log-normal behavior. We interpret the grain reorganization dynamics using a stochastic model.

Intrinsic Atomic Orbitals: An Unbiased Bridge between Quantum Theory and Chemical Concepts.

PubMed

Knizia, Gerald

2013-11-12

Modern quantum chemistry can make quantitative predictions on an immense array of chemical systems. However, the interpretation of those predictions is often complicated by the complex wave function expansions used. Here we show that an exceptionally simple algebraic construction allows for defining atomic core and valence orbitals, polarized by the molecular environment, which can exactly represent self-consistent field wave functions. This construction provides an unbiased and direct connection between quantum chemistry and empirical chemical concepts, and can be used, for example, to calculate the nature of bonding in molecules, in chemical terms, from first principles. In particular, we find consistency with electronegativities (χ), C 1s core-level shifts, resonance substituent parameters (σR), Lewis structures, and oxidation states of transition-metal complexes.

Quantum-chemical investigations of spectroscopic properties of a fluorescence probe

NASA Astrophysics Data System (ADS)

Titova, T. Yu.; Morozova, Yu. P.; Zharkova, O. M.; Artyukhov, V. Ya.; Korolev, B. V.

2012-09-01

The prodan molecule (6-propionyl-2-dimethylamino naphthalene) - fluorescence probe - is investigated by quantum-chemical methods of intermediate neglect of differential overlap (INDO) and molecular electrostatic potential (MEP). The dipole moments of the ground and excited states, the nature and position of energy levels, the centers of specific solvation, the rate constants of photoprocesses, and the fluorescence quantum yield are estimated. To elucidate the role of the dimethylamino group in the formation of bands and spectral characteristics, the molecule only with the propionyl group (pron) is investigated. The long-wavelength absorption bands of prodan and pron molecules are interpreted. The results obtained for the prodan molecule by the INDO method with original spectroscopic parameterization are compared with the literature data obtained by the DFT/CIS, ZINDO/S, and AM1/CISD methods.

A molecular logic gate.

PubMed

Kompa, K L; Levine, R D

2001-01-16

We propose a scheme for molecule-based information processing by combining well-studied spectroscopic techniques and recent results from chemical dynamics. Specifically it is discussed how optical transitions in single molecules can be used to rapidly perform classical (Boolean) logical operations. In the proposed way, a restricted number of states in a single molecule can act as a logical gate equivalent to at least two switches. It is argued that the four-level scheme can also be used to produce gain, because it allows an inversion, and not only a switching ability. The proposed scheme is quantum mechanical in that it takes advantage of the discrete nature of the energy levels but, we here discuss the temporal evolution, with the use of the populations only. On a longer time range we suggest that the same scheme could be extended to perform quantum logic, and a tentative suggestion, based on an available experiment, is discussed. We believe that the pumping can provide a partial proof of principle, although this and similar experiments were not interpreted thus far in our terms.

Experimental and theoretical study on free 5-nitroquinoline, 5-nitroisoquinoline, and their zinc(II) halide complexes

NASA Astrophysics Data System (ADS)

Yurdakul, Şenay; Badoğlu, Serdar; Güleşci, Yeliz

2015-02-01

In this study where the interpretations of the experimental IR and Raman spectra recorded at room temperature for the ligands 5-nitroquinoline (5NQ) and 5-nitroisoquinoline (5NIQ) and also for their Zn(II) halide (halogen: chlorine, bromine, iodine) complexes were first reported, the assignments of the observed fundamental bands were achieved in the light of the vibrational spectral data and total energy distribution (TED) values calculated at B3LYP/6-311++G(d,p) and B3LYP/LANL2DZ levels of theory. The equilibrium geometrical parameters, Natural Bond Orbital (NBO) charges and frontier orbital (HOMO, LUMO) energies of these molecular structures were also calculated at the same level of theory. Comparisons over the corresponding experimental and theoretical data obtained for the title ligands and their complexes revealed that in complex form both ligands bond to Zn(II) ion through their ring nitrogen atoms and NO2 groups at the same time.

Incorporating personalized gene sequence variants, molecular genetics knowledge, and health knowledge into an EHR prototype based on the Continuity of Care Record standard.

PubMed

Jing, Xia; Kay, Stephen; Marley, Thomas; Hardiker, Nicholas R; Cimino, James J

2012-02-01

The current volume and complexity of genetic tests, and the molecular genetics knowledge and health knowledge related to interpretation of the results of those tests, are rapidly outstripping the ability of individual clinicians to recall, understand and convey to their patients information relevant to their care. The tailoring of molecular genetics knowledge and health knowledge in clinical settings is important both for the provision of personalized medicine and to reduce clinician information overload. In this paper we describe the incorporation, customization and demonstration of molecular genetic data (mainly sequence variants), molecular genetics knowledge and health knowledge into a standards-based electronic health record (EHR) prototype developed specifically for this study. We extended the CCR (Continuity of Care Record), an existing EHR standard for representing clinical data, to include molecular genetic data. An EHR prototype was built based on the extended CCR and designed to display relevant molecular genetics knowledge and health knowledge from an existing knowledge base for cystic fibrosis (OntoKBCF). We reconstructed test records from published case reports and represented them in the CCR schema. We then used the EHR to dynamically filter molecular genetics knowledge and health knowledge from OntoKBCF using molecular genetic data and clinical data from the test cases. The molecular genetic data were successfully incorporated in the CCR by creating a category of laboratory results called "Molecular Genetics" and specifying a particular class of test ("Gene Mutation Test") in this category. Unlike other laboratory tests reported in the CCR, results of tests in this class required additional attributes ("Molecular Structure" and "Molecular Position") to support interpretation by clinicians. These results, along with clinical data (age, sex, ethnicity, diagnostic procedures, and therapies) were used by the EHR to filter and present molecular genetics knowledge and health knowledge from OntoKBCF. This research shows a feasible model for delivering patient sequence variants and presenting tailored molecular genetics knowledge and health knowledge via a standards-based EHR system prototype. EHR standards can be extended to include the necessary patient data (as we have demonstrated in the case of the CCR), while knowledge can be obtained from external knowledge bases that are created and maintained independently from the EHR. This approach can form the basis for a personalized medicine framework, a more comprehensive standards-based EHR system and a potential platform for advancing translational research by both disseminating results and providing opportunities for new insights into phenotype-genotype relationships. Copyright © 2011 Elsevier Inc. All rights reserved.

Dielectric properties of crystalline organic molecular films in the limit of zero overlap

DOE Office of Scientific and Technical Information (OSTI.GOV)

D’Avino, Gabriele, E-mail: gabriele.davino@gmail.com; Vanzo, Davide; Soos, Zoltán G., E-mail: soos@princeton.edu

2016-01-21

We present the calculation of the static dielectric susceptibility tensor and dipole field sums in thin molecular films in the well-defined limit of zero intermolecular overlap. Microelectrostatic and charge redistribution approaches are applied to study the evolution of dielectric properties from one to a few molecular layers in films of different conjugated molecules with organic electronics applications. Because of the conditional convergence of dipolar interactions, dipole fields depend on the shape of the sample and different values are found in the middle layer of a thick film and in the bulk. The shape dependence is eliminated when depolarization is takenmore » into account, and the dielectric tensor of molecular films converges to the bulk limit within a few molecular layers. We quantify the magnitude of surface effects and interpret general trends among different systems in terms of molecular properties, such as shape, polarizability anisotropy, and supramolecular organization. A connection between atomistic models for molecular dielectrics and simpler theories for polarizable atomic lattices is also provided.« less

Gas-rich galaxy pair unveiled in the lensed quasar 0957+561

PubMed

Planesas; Martin-Pintado; Neri; Colina

1999-12-24

Molecular gas in the host galaxy of the lensed quasar 0957+561 (QSO 0957+561) at the redshift of 1.41 has been detected in the carbon monoxide (CO) line. This detection shows the extended nature of the molecular gas distribution in the host galaxy and the pronounced lensing effects due to the differentially magnified CO luminosity at different velocities. The estimated mass of molecular gas is about 4 x 10(9) solar masses, a molecular gas mass typical of a spiral galaxy like the Milky Way. A second, weaker component of CO is interpreted as arising from a close companion galaxy that is rich in molecular gas and has remained undetected so far. Its estimated molecular gas mass is 1.4 x 10(9) solar masses, and its velocity relative to the main galaxy is 660 kilometers per second. The ability to probe the molecular gas distribution and kinematics of galaxies associated with high-redshift lensed quasars can be used to improve the determination of the Hubble constant H(0).

Liquid-Vapor Interfacial Properties of Aqueous Solutions of Guanidinium and Methyl Guanidinium Chloride: Influence of Molecular Orientation on Interface Fluctuations

PubMed Central

Ou, Shuching; Cui, Di; Patel, Sandeep

2014-01-01

The guanidinium cation (C(NH2)3+) is a highly stable cation in aqueous solution due to its efficient solvation by water molecules and resonance stabilization of the charge. Its salts increase the solubility of nonpolar molecules (”salting-in”) and decrease the ordering of water. It is one of the strongest denaturants used in biophysical studies of protein folding. We investigate the behavior of guanidinium and its derivative, methyl guanidinium (an amino acid analogue) at the air-water surface, using atomistic molecular dynamics (MD) simulations and calculation of potentials of mean force. Methyl guanidinium cation is less excluded from the air-water surface than guanidinium cation, but both cations show orientational dependence of surface affinity. Parallel orientations of the guanidinium ring (relative to the Gibbs dividing surface) show pronounced free energy minima in the interfacial region, while ring orientations perpendicular to the GDS exhibit no discernible surface stability. Calculations of surface fluctuations demonstrate that near the air-water surface, the parallel-oriented cations generate significantly greater interfacial fluctuations compared to other orientations, which induces more long-ranged perturbations and solvent density redistribution. Our results suggest a strong correlation with induced interfacial fluctuations and ion surface stability. These results have implications for interpreting molecular-level, mechanistic action of this osmolyte’s interaction with hydrophobic interfaces as they impact protein denaturation (solubilization). PMID:23937431

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations

PubMed Central

Ahlstrom, Logan S.; Vorontsov, Ivan I.; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations. PMID:28107510

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations.

PubMed

Ahlstrom, Logan S; Vorontsov, Ivan I; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.

Figure analysis: A teaching technique to promote visual literacy and active Learning.

PubMed

Wiles, Amy M

2016-07-08

Learning often improves when active learning techniques are used in place of traditional lectures. For many of these techniques, however, students are expected to apply concepts that they have already grasped. A challenge, therefore, is how to incorporate active learning into the classroom of courses with heavy content, such as molecular-based biology courses. An additional challenge is that visual literacy is often overlooked in undergraduate science education. To address both of these challenges, a technique called figure analysis was developed and implemented in three different levels of undergraduate biology courses. Here, students learn content while gaining practice in interpreting visual information by discussing figures with their peers. Student groups also make connections between new and previously learned concepts on their own while in class. The instructor summarizes the material for the class only after students grapple with it in small groups. Students reported a preference for learning by figure analysis over traditional lecture, and female students in particular reported increased confidence in their analytical abilities. There is not a technology requirement for this technique; therefore, it may be utilized both in classrooms and in nontraditional spaces. Additionally, the amount of preparation required is comparable to that of a traditional lecture. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):336-344, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

History in the gene: negotiations between molecular and organismal anthropology.

PubMed

Sommer, Marianne

2008-01-01

In the advertising discourse of human genetic database projects, of genetic ancestry tracing companies, and in popular books on anthropological genetics, what I refer to as the anthropological gene and genome appear as documents of human history, by far surpassing the written record and oral history in scope and accuracy as archives of our past. How did macromolecules become "documents of human evolutionary history"? Historically, molecular anthropology, a term introduced by Emile Zuckerkandl in 1962 to characterize the study of primate phylogeny and human evolution on the molecular level, asserted its claim to the privilege of interpretation regarding hominoid, hominid, and human phylogeny and evolution vis-à-vis other historical sciences such as evolutionary biology, physical anthropology, and paleoanthropology. This process will be discussed on the basis of three key conferences on primate classification and evolution that brought together exponents of the respective fields and that were held in approximately ten-years intervals between the early 1960s and the 1980s. I show how the anthropological gene and genome gained their status as the most fundamental, clean, and direct records of historical information, and how the prioritizing of these epistemic objects was part of a complex involving the objectivity of numbers, logic, and mathematics, the objectivity of machines and instruments, and the objectivity seen to reside in the epistemic objects themselves.

Molecular structure, vibrational, electronic and thermal properties of 4-vinylcyclohexene by quantum chemical calculations

NASA Astrophysics Data System (ADS)

Nagabalasubramanian, P. B.; Periandy, S.; Karabacak, Mehmet; Govindarajan, M.

2015-06-01

The solid phase FT-IR and FT-Raman spectra of 4-vinylcyclohexene (abbreviated as 4-VCH) have been recorded in the region 4000-100 cm-1. The optimized molecular geometry and vibrational frequencies of the fundamental modes of 4-VCH have been precisely assigned and analyzed with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) method at 6-311++G(d,p) level basis set. The theoretical frequencies were properly scaled and compared with experimentally obtained FT-IR and FT-Raman spectra. Also, the effect due the substitution of vinyl group on the ring vibrational frequencies was analyzed and a detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated total energy distribution (TED). The time dependent DFT (TD-DFT) method was employed to predict its electronic properties, such as electronic transitions by UV-Visible analysis, HOMO and LUMO energies, molecular electrostatic potential (MEP) and various global reactivity and selectivity descriptors (chemical hardness, chemical potential, softness, electrophilicity index). Stability of the molecule arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Atomic charges obtained by Mulliken population analysis and NBO analysis are compared. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound at different temperatures are also calculated.

The spontaneous synchronized dance of pairs of water molecules

NASA Astrophysics Data System (ADS)

Roncaratti, Luiz F.; Cappelletti, David; Pirani, Fernando

2014-03-01

Molecular beam scattering experiments have been performed to study the effect of long-range anisotropic forces on the collision dynamics of two small polar molecules. The main focus of this paper is on water, but also ammonia and hydrogen sulphide molecules have been investigated, and some results will be anticipated. The intermolecular distances mainly probed are of the order of 1 nm and therefore much larger than the molecular dimensions. In particular, we have found that the natural electric field gradient, generated by different spatial orientations of the permanent electric dipoles, is able to promote the transformation of free rotations into coupled pendular states, letting the molecular partners involved in the collision complex swinging to and fro around the field direction. This long-ranged concerted motion manifested itself as large increases of the magnitude of the total integral cross section. The experimental findings and the theoretical treatment developed to shed light on the details of the process suggest that the transformation from free rotations to pendular states depends on the rotational level of both molecules, on the impact parameter, on the relative collision velocity, on the dipole moment product and occurs in the time scale of picoseconds. The consequences of this intriguing phenomenon may be important for the interpretation and, in perspective, for the control of elementary chemical and biological processes, given by polar molecules, ions, and free radicals, occurring in several environments under various conditions.

SM2PH-db: an interactive system for the integrated analysis of phenotypic consequences of missense mutations in proteins involved in human genetic diseases.

PubMed

Friedrich, Anne; Garnier, Nicolas; Gagnière, Nicolas; Nguyen, Hoan; Albou, Laurent-Philippe; Biancalana, Valérie; Bettler, Emmanuel; Deléage, Gilbert; Lecompte, Odile; Muller, Jean; Moras, Dino; Mandel, Jean-Louis; Toursel, Thierry; Moulinier, Luc; Poch, Olivier

2010-02-01

Understanding how genetic alterations affect gene products at the molecular level represents a first step in the elucidation of the complex relationships between genotypic and phenotypic variations, and is thus a major challenge in the postgenomic era. Here, we present SM2PH-db (http://decrypthon.igbmc.fr/sm2ph), a new database designed to investigate structural and functional impacts of missense mutations and their phenotypic effects in the context of human genetic diseases. A wealth of up-to-date interconnected information is provided for each of the 2,249 disease-related entry proteins (August 2009), including data retrieved from biological databases and data generated from a Sequence-Structure-Evolution Inference in Systems-based approach, such as multiple alignments, three-dimensional structural models, and multidimensional (physicochemical, functional, structural, and evolutionary) characterizations of mutations. SM2PH-db provides a robust infrastructure associated with interactive analysis tools supporting in-depth study and interpretation of the molecular consequences of mutations, with the more long-term goal of elucidating the chain of events leading from a molecular defect to its pathology. The entire content of SM2PH-db is regularly and automatically updated thanks to a computational grid data federation facilities provided in the context of the Decrypthon program. (c) 2009 Wiley-Liss, Inc.

Molecular Characterization of Transgene Integration by Next-Generation Sequencing in Transgenic Cattle

PubMed Central

Zhang, Ran; Yin, Yinliang; Zhang, Yujun; Li, Kexin; Zhu, Hongxia; Gong, Qin; Wang, Jianwu; Hu, Xiaoxiang; Li, Ning

2012-01-01

As the number of transgenic livestock increases, reliable detection and molecular characterization of transgene integration sites and copy number are crucial not only for interpreting the relationship between the integration site and the specific phenotype but also for commercial and economic demands. However, the ability of conventional PCR techniques to detect incomplete and multiple integration events is limited, making it technically challenging to characterize transgenes. Next-generation sequencing has enabled cost-effective, routine and widespread high-throughput genomic analysis. Here, we demonstrate the use of next-generation sequencing to extensively characterize cattle harboring a 150-kb human lactoferrin transgene that was initially analyzed by chromosome walking without success. Using this approach, the sites upstream and downstream of the target gene integration site in the host genome were identified at the single nucleotide level. The sequencing result was verified by event-specific PCR for the integration sites and FISH for the chromosomal location. Sequencing depth analysis revealed that multiple copies of the incomplete target gene and the vector backbone were present in the host genome. Upon integration, complex recombination was also observed between the target gene and the vector backbone. These findings indicate that next-generation sequencing is a reliable and accurate approach for the molecular characterization of the transgene sequence, integration sites and copy number in transgenic species. PMID:23185606

Collisional excitation of molecules in dense interstellar clouds

NASA Technical Reports Server (NTRS)

Green, S.

1985-01-01

State transitions which permit the identification of the molecular species in dense interstellar clouds are reviewed, along with the techniques used to calculate the transition energies, the database on known molecular transitions and the accuracy of the values. The transition energies cannot be measured directly and therefore must be modeled analytically. Scattering theory is used to determine the intermolecular forces on the basis of quantum mechanics. The nuclear motions can also be modeled with classical mechanics. Sample rate constants are provided for molecular systems known to inhabit dense interstellar clouds. The values serve as a database for interpreting microwave and RF astrophysical data on the transitions undergone by interstellar molecules.

Novel primer specific false terminations during DNA sequencing reactions: danger of inaccuracy of mutation analysis in molecular diagnostics

PubMed Central

Anwar, R; Booth, A; Churchill, A J; Markham, A F

1996-01-01

The determination of nucleotide sequence is fundamental to the identification and molecular analysis of genes. Direct sequencing of PCR products is now becoming a commonplace procedure for haplotype analysis, and for defining mutations and polymorphism within genes, particularly for diagnostic purposes. A previously unrecognised phenomenon, primer related variability, observed in sequence data generated using Taq cycle sequencing and T7 Sequenase sequencing, is reported. This suggests that caution is necessary when interpreting DNA sequence data. This is particularly important in situations where treatment may be dependent on the accuracy of the molecular diagnosis. Images PMID:16696096

Preventing iron(ii) precipitation in aqueous systems using polyacrylic acid: some molecular insights.

PubMed

Artola, Pierre-Arnaud; Rousseau, Bernard; Clavaguéra, Carine; Roy, Marion; You, Dominique; Plancque, Gabriel

2018-06-22

We present molecular dynamics simulations of aqueous iron(ii) systems in the presence of polyacrylic acid (PAA) under the extreme conditions that take place in the secondary coolant circuit of a nuclear power plant. The aim of this work is to understand how the oligomer can prevent iron(ii) deposits, and to provide molecular interpretation. We show how, to this end, not only the complexant ability is necessary, but also the chain length compared to iron(ii) concentration. When the chain is long enough, a hyper-complexation phenomenon occurs that can explain the specific capacity of the polymer to prevent iron(ii) precipitation.

Molecular Dynamics Simulations of Nucleic Acids. From Tetranucleotides to the Ribosome.

PubMed

Šponer, Jiří; Banáš, Pavel; Jurečka, Petr; Zgarbová, Marie; Kührová, Petra; Havrila, Marek; Krepl, Miroslav; Stadlbauer, Petr; Otyepka, Michal

2014-05-15

We present a brief overview of explicit solvent molecular dynamics (MD) simulations of nucleic acids. We explain physical chemistry limitations of the simulations, namely, the molecular mechanics (MM) force field (FF) approximation and limited time scale. Further, we discuss relations and differences between simulations and experiments, compare standard and enhanced sampling simulations, discuss the role of starting structures, comment on different versions of nucleic acid FFs, and relate MM computations with contemporary quantum chemistry. Despite its limitations, we show that MD is a powerful technique for studying the structural dynamics of nucleic acids with a fast growing potential that substantially complements experimental results and aids their interpretation.

Viscosity minima in binary mixtures of ionic liquids + molecular solvents.

PubMed

Tariq, M; Shimizu, K; Esperança, J M S S; Canongia Lopes, J N; Rebelo, L P N

2015-05-28

The viscosity (η) of four binary mixtures (ionic liquids plus molecular solvents, ILs+MSs) was measured in the 283.15 < T/K < 363.15 temperature range. Different IL/MS combinations were selected in such a way that the corresponding η(T) functions exhibit crossover temperatures at which both pure components present identical viscosity values. Consequently, most of the obtained mixture isotherms, η(x), exhibit clear viscosity minima in the studied T-x range. The results are interpreted using auxiliary molecular dynamics (MD) simulation data in order to correlate the observed η(T,x) trends with the interactions in each mixture, including the balance between electrostatic forces and hydrogen bonding.

Single molecular orientation switching of an endohedral metallofullerene.

PubMed

Yasutake, Yuhsuke; Shi, Zujin; Okazaki, Toshiya; Shinohara, Hisanori; Majima, Yutaka

2005-06-01

The single molecular orientation switching of the Tb@C82 endohedral metallofullerene has been studied by using low-temperature ultrahigh vacuum (UHV) scanning tunneling microscopy (STM). An octanethiol self-assembled monolayer (SAM) was introduced between Tb@C82 and the Au111 substrate to control the thermal rotational states of Tb@C82. Scanning tunneling spectroscopy (STS) of Tb@C82 on an octanethiol SAM at 13 K demonstrated hysteresis including negative differential conductance (NDC). This observed hysteresis and NDC is interpreted in terms of a switching of the Tb@C82 molecular orientation caused by the interaction between its electric dipole moment and an external electric field.

Laser spectroscopic visualization of hydrogen bond motions in liquid water

NASA Astrophysics Data System (ADS)

Bratos, S.; Leicknam, J.-Cl.; Pommeret, S.; Gallot, G.

2004-12-01

Ultrafast pump-probe experiments are described permitting a visualization of molecular motions in diluted HDO/D 2O solutions. The experiments were realized in the mid-infrared spectral region with a time resolution of 150 fs. They were interpreted by a careful theoretical analysis, based on the correlation function approach of statistical mechanics. Combining experiment and theory, stretching motions of the OH⋯O bonds as well as HDO rotations were 'filmed' in real time. It was found that molecular rotations are the principal agent of hydrogen bond breaking and making in water. Recent literatures covering the subject, including molecular dynamics simulations, are reviewed in detail.

Effect of the asymmetry of the coupling of the redox molecule to the electrodes in the one-level electrochemical bridged tunneling contact on the Coulomb blockade and the operation of molecular transistor.

PubMed

Medvedev, Igor G

2014-09-28

Effect of the asymmetry of the redox molecule (RM) coupling to the working electrodes on the Coulomb blockade and the operation of molecular transistor is considered under ambient conditions for the case of the non-adiabatic tunneling through the electrochemical contact having a one-level RM. The expressions for the tunnel current, the positions of the peaks of the tunnel current/overpotential dependencies, and their full widths at the half maximum are obtained for arbitrary values of the parameter d describing the coupling asymmetry of the tunneling contact and the effect of d on the different characteristics of the tunneling contact is studied. The tunnel current/overpotential and the differential conductance/bias voltage dependencies are calculated and interpreted. In particular, it is shown that the effect of the Coulomb blockade on the tunnel current and the differential conductance has a number of new features in the case of the large coupling asymmetry. It is also shown that, for rather large values of the solvent reorganization energy, the coupling asymmetry enhanced strongly amplification and rectification of the tunnel current in the most of the regions of the parameter space specifying the tunneling contact. The regions of the parameter space where both strong amplification and strong rectification take place are also revealed. The obtained results allow us to prove the possibility of the realization of the effective electrochemical transistor based on the one-level RM.

Structure of Hydrated Poly(d,l-lactic acid) Studied with X-ray Diffraction and Molecular Simulation Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xianfeng; Murthy, N. Sanjeeva; Latour, Robert A.

2012-10-10

The effect of hydration on the molecular structure of amorphous poly(D,L-lactic acid) (PDLLA) with 50:50 L-to-D ratio has been studied by combining experiments with molecular simulations. X-ray diffraction measurements revealed significant changes upon hydration in the structure functions of the copolymer. Large changes in the structure functions at 10 days of incubation coincided with the large increase in the water uptake from {approx} 1 to {approx} 40% and the formation of voids in the film. Computer modeling based on the recently developed TIGER2/TIGER3 mixed sampling scheme was used to interpret these changes by efficiently equilibrating both dry and hydrated modelsmore » of PDLLA. Realistic models of bulk amorphous PDLLA structure were generated as demonstrated by close agreement between the calculated and the experimental structure functions. These molecular simulations were used to identify the interactions between water and the polymer at the atomic level including the change of positional order between atoms in the polymer due to hydration. Changes in the partial O-O structure functions, about 95% of which were due to water-polymer interactions, were apparent in the radial distribution functions. These changes, and somewhat smaller changes in the C-C and C-O partial structure functions, clearly demonstrated the ability of the model to capture the hydrogen-bonding interactions between water and the polymer, with the probability of water forming hydrogen bonds with the carbonyl oxygen of the ester group being about 4 times higher than with its ether oxygen.« less

Laser-Induced Molecular Fluorescence: A Physical Chemistry Experiment.

ERIC Educational Resources Information Center

Tellinghuisen, Joel

1981-01-01

Describes a companion experiment to the experimental study of the di-iodide visible absorption spectrum. Experimental details, interpretation, and data analysis are provided for an analysis of the di-iodide fluorescence excited by a visible laser, using a Raman instrument. (CS)

Fundamentals of nutrigenetics and nutrigenomics

USDA-ARS?s Scientific Manuscript database

This volume of Progress in Molecular Biology and Translational Science is devoted to the exciting and promising field of nutrigenetics and nutrigenomics. The introductory chapter defines the basic concepts necessary for the interpretation of the material covered in the remainder of the volume. Empha...

Bohm's Quantum Potential and the Visualization of Molecular Structure

NASA Technical Reports Server (NTRS)

Levit, Creon; Chancellor, Marisa K. (Technical Monitor)

1997-01-01

David Bohm's ontological interpretation of quantum theory can shed light on otherwise counter-intuitive quantum mechanical phenomena including chemical bonding. In the field of quantum chemistry, Richard Bader has shown that the topology of the Laplacian of the electronic charge density characterizes many features of molecular structure and reactivity. Visual and computational examination suggests that the Laplacian of Bader and the quantum potential of Bohm are morphologically equivalent. It appears that Bohmian mechanics and the quantum potential can make chemistry as clear as they makes physics.

Computer Code for Interpreting 13C NMR Relaxation Measurements with Specific Models of Molecular Motion: The Rigid Isotropic and Symmetric Top Rotor Models and the Flexible Symmetric Top Rotor Model

DTIC Science & Technology

2017-01-01

unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT: Carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy is a powerful technique for...FLEXIBLE SYMMETRIC TOP ROTOR MODEL 1. INTRODUCTION Nuclear magnetic resonance (NMR) spectroscopy is a tremendously powerful technique for...application of NMR spectroscopy concerns the property of molecular motion, which is related to many physical, and even biological, functions of molecules in

CPTAC Develops LinkedOmics – Public Web Portal to Analyze Multi-Omics Data Within and Across Cancer Types | Office of Cancer Clinical Proteomics Research

Cancer.gov

Multi-omics analysis has grown in popularity among biomedical researchers given the comprehensive characterization of thousands of molecular attributes in addition to clinical attributes. Several data portals have been devised to make these datasets directly available to the cancer research community. However, none of the existing data portals allow systematic exploration and interpretation of the complex relationships between the vast amount of clinical and molecular attributes. CPTAC investigator Dr.

Reading the Molecular Code in Soils

NASA Astrophysics Data System (ADS)

Hess, N. J.; Tfaily, M. M.; O'Brien, S. L.; Tolic, N.; Jastrow, J. D.; Amonette, J. E.

2015-12-01

There is much that we understand about the relationship between plants, microbes, soil, and water but that understanding is incomplete at the molecular scale. With advent of high throughput genomic sequencing we are beginning to appreciate the diversity of microbial community structure and function and its response to the rhythm of plant function. Through the lens of high-resolution mass spectrometry we are getting our first glimpses of the diversity of soil and pore water organic chemistry at the molecular level. In combination, these diverse data streams are revealing traces of chemical metabolic pathways. This approach promises to reveal many exciting future discoveries, shedding light into the "black box" that exists beneath our feet. In this talk we discuss our experience with the molecular characterization of soils from native prairie to restored prairie to active corn-soybean soils from the DOE funded CSiTE project in Batavia, Illinois. We focus on how common soil separation and fractionation techniques can affect the resulting molecular soil characterization by comparing whole soils to those that have been fractionated into micro- and macro-aggregates and their corresponding silt and clay fractions. When carefully utilized and interpreted these fractionation techniques can be utilized for deepening understanding of the biotic and abiotic chemical pathways effecting the organic chemistry in the different soil fractions. In highly fractionated soils we find significant differences in organic chemistry between silt and clay separates of corresponding hierarchical aggregate fractions. However the most biologically rich information resides in the whole soil. Here we see significant gradients in soil chemistry across to active agricultural to restored to native prairie soils. These results suggest a cautionary note, namely that soil fractionation prior to molecular characterization can reveal much about the "abiotic" interactions between organic molecules and soil minerals but the much of the "biotic" story resides in the whole soil.

Evolution of L -shell photoabsorption of the molecular-ion series Si Hn + (n =1 ,2 ,3 ): Experimental and theoretical studies

NASA Astrophysics Data System (ADS)

Kennedy, E. T.; Mosnier, J.-P.; van Kampen, P.; Bizau, J.-M.; Cubaynes, D.; Guilbaud, S.; Carniato, S.; Puglisi, A.; Sisourat, N.

2018-04-01

We report on complementary laboratory and theoretical investigations of the 2 p photoexcitation cross sections for the molecular-ion series Si Hn + (n =1 ,2 ,3 ) near the L -shell threshold. The experiments used an electron cyclotron resonance (ECR) plasma molecular-ion source coupled with monochromatized synchrotron radiation in a merged-beam configuration. For all three molecular ions, the S i2 + decay channel appeared dominant, suggesting similar electronic and nuclear relaxation patterns involving resonant Auger and dissociation processes, respectively. The total yields of the S i2 + products were recorded and put on absolute cross-section scales by comparison with the spectrum of the S i+ parent atomic ion. Interpretation of the experimental spectra ensued from a comparison with total photoabsorption cross-sectional profiles calculated using ab initio configuration interaction theoretical methods inclusive of vibrational dynamics and contributions from inner-shell excitations in both ground and valence-excited electronic states. The spectra, while broadly similar for all three molecular ions, moved towards lower energies as the number of screening hydrogen atoms increased from one to three. They featured a wide and shallow region below ˜107 eV due to 2 p →σ* transitions to dissociative states, and intense and broadened peaks in the ˜107 -113 -eV region merging into sharp Rydberg series due to 2 p →n δ ,n π transitions converging on the LII ,III limits above ˜113 eV . This overall spectral shape is broadly replicated by theory in each case, but the level of agreement does not extend to individual resonance structures. In addition to the fundamental interest, the work should also prove useful for the understanding and modeling of astronomical and laboratory plasma sources where silicon hydride molecular species play significant roles.

Is the molecular diversity of marine dissolved organic matter already imprinted in the exometabolome of single strains?

NASA Astrophysics Data System (ADS)

Noriega-Ortega, B. E.; Wienhausen, G.; Dittmar, T.; Simon, M.; Niggemann, J.

2016-02-01

Dissolved organic matter (DOM) in the ocean, the marine geometabolome, is an extremely complex mixture composed of a wide variety of compounds. The molecular chemodiversity affects the function and turnover rate of DOM in the ocean. We hypothesize that the active microbial community essentially contributes to the complexity of the DOM pool through uptake and excretion of compounds. We tested this hypothesis in culture experiments with fully-sequenced strains of the Roseobacter clade. Bacteria of the Roseobacter clade are among the most abundant microbial players in the ocean. We studied the exometabolome of two representatives of the Roseobacter clade, Phaeobacter inhibens DSM 17395 and Dinoroseobacter shibae. The organisms were grown separately in cultures on defined single model substrates (acetate, succinate, glutamate, glucose). We used a non-targeted analytical approach via Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to characterize the exometabolome at the molecular level, complemented by compound-specific analyses of free and combined amino acids and carbohydrates. The exometabolome composition varied between the tested strains, which released a different suite of compounds depending on the growth phase as well as on growth conditions (substrate). Both organisms exhibited a core exometabolome with compounds released when growing on either substrate and at all growth phases, and a variable exometabolome specific for different substrates and growth phases. However, only a small fraction of the exometabolites detected by FT-ICR-MS could be directly linked to the genome or transcriptome. We interpret these findings as evidence for the excretion of molecularly highly-diverse metabolic waste, whose composition is dependent on the metabolic state and genetic repertoire of the organisms. The molecular diversity of compounds excreted by a single strain is extraordinary and is likely the reason for the molecular diversity of natural DOM in the ocean.

Indices of agreement between neurosurgeons and a radiologist in interpreting tomography scans in an emergency department.

PubMed

Dourado, Jules Carlos; Pereira, Júlio Leonardo Barbosa; Albuquerque, Lucas Alverne Freitas de; Carvalho, Gervásio Teles Cardos de; Dias, Patrícia; Dias, Laura; Bicalho, Marcos; Magalhães, Pollyana; Dellaretti, Marcos

2015-08-01

The power of interpretation in the analysis of cranial computed tomography (CCT) among neurosurgeons and radiologists has rarely been studied. This study aimed to assess the rate of agreement in the interpretation of CCTs between neurosurgeons and a radiologist in an emergency department. 227 CCT were independently analyzed by two neurosurgeons (NS1 and NS2) and a radiologist (RAD). The level of agreement in interpreting the examination was studied. The Kappa values obtained between NS1 and NS2 and RAD were considered nearly perfect and substantial agreement. The highest levels of agreement when evaluating abnormalities were observed in the identification of tumors, hydrocephalus and intracranial hematomas. The worst levels of agreement were observed for leukoaraiosis and reduced brain volume. For diseases in which the emergency room procedure must be determined, agreement in the interpretation of CCTs between the radiologist and neurosurgeons was satisfactory.

How to address patients' defences: a pilot study of the accuracy of defence interpretations and alliance.

PubMed

Junod, Olivier; de Roten, Yves; Martinez, Elena; Drapeau, Martin; Despland, Jean-Nicolas

2005-12-01

This pilot study examined the accuracy of therapist defence interpretations (TAD) in high-alliance patients (N = 7) and low-alliance patients (N = 8). TAD accuracy was assessed in the two subgroups by comparing for each case the patient's most frequent defensive level with the most frequent defensive level addressed by the therapist when making defence interpretations. Results show that in high-alliance patient-therapist dyads, the therapists tend to address accurate or higher (more mature) defensive level than patients most frequent level. On the other hand, the therapists address lower (more immature) defensive level in low-alliance dyads. These results are discussed along with possible ways to better assess TAD accuracy.

Perchlorate-induced combustion of organic matter with variable molecular weights: Implications for Mars missions

NASA Astrophysics Data System (ADS)

Sephton, Mark A.; Lewis, James M. T.; Watson, Jonathan S.; Montgomery, Wren; Garnier, Carole

2014-11-01

Instruments on the Viking landers and Curiosity rover analyzed samples of Mars and detected carbon dioxide and organic compounds of uncertain origin. Mineral-assisted reactions are leading to uncertainty, particularly those involving perchlorate minerals which thermally decompose to produce chlorine and oxygen which can then react with organic matter to generate organochlorine compounds and carbon dioxide. Although generally considered a problem for interpretation, the release profiles of generated gases can indicate the type of organic matter present. We have performed a set of experiments with perchlorate and organic matter of variable molecular weights. Results indicate that organic susceptibility to thermal degradation and mineral-assisted reactions is related to molecular weight. Low molecular weight organic matter reacts at lower temperatures than its high molecular weight counterparts. The natural occurrence and association of organic matter with differing molecular weights helps to discriminate between contamination (usually low molecular weight organic matter only) and indigenous carbon (commonly low and high molecular weight organic matter together). Our results can be used to provide insights into data returning from Mars.

Setting a standard: the limulus amebocyte lysate assay and the assessment of microbial contamination on spacecraft surfaces.

PubMed

Morris, Heather C; Monaco, Lisa A; Steele, Andrew; Wainwright, Norm

2010-10-01

Historically, colony-forming units as determined by plate cultures have been the standard unit for microbiological analysis of environmental samples, medical diagnostics, and products for human use. However, the time and materials required make plate cultures expensive and potentially hazardous in the closed environments of future NASA missions aboard the International Space Station and missions to other Solar System targets. The Limulus Amebocyte Lysate (LAL) assay is an established method for ensuring the sterility and cleanliness of samples in the meat-packing and pharmaceutical industries. Each of these industries has verified numerical requirements for the correct interpretation of results from this assay. The LAL assay is a rapid, point-of-use, verified assay that has already been approved by NASA Planetary Protection as an alternate, molecular method for the examination of outbound spacecraft. We hypothesize that standards for molecular techniques, similar to those used by the pharmaceutical and meat-packing industries, need to be set by space agencies to ensure accurate data interpretation and subsequent decision making. In support of this idea, we present research that has been conducted to relate the LAL assay to plate cultures, and we recommend values obtained from these investigations that could assist in interpretation and analysis of data obtained from the LAL assay.

Biochemical interpretation of quantitative structure-activity relationships (QSAR) for biodegradation of N-heterocycles: a complementary approach to predict biodegradability.

PubMed

Philipp, Bodo; Hoff, Malte; Germa, Florence; Schink, Bernhard; Beimborn, Dieter; Mersch-Sundermann, Volker

2007-02-15

Prediction of the biodegradability of organic compounds is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. We combined quantitative structure-activity relationships (QSAR) with the systematic collection of biochemical knowledge to establish rules for the prediction of aerobic biodegradation of N-heterocycles. Validated biodegradation data of 194 N-heterocyclic compounds were analyzed using the MULTICASE-method which delivered two QSAR models based on 17 activating (OSAR 1) and on 16 inactivating molecular fragments (GSAR 2), which were statistically significantly linked to efficient or poor biodegradability, respectively. The percentages of correct classifications were over 99% for both models, and cross-validation resulted in 67.9% (GSAR 1) and 70.4% (OSAR 2) correct predictions. Biochemical interpretation of the activating and inactivating characteristics of the molecular fragments delivered plausible mechanistic interpretations and enabled us to establish the following biodegradation rules: (1) Target sites for amidohydrolases and for cytochrome P450 monooxygenases enhance biodegradation of nonaromatic N-heterocycles. (2) Target sites for molybdenum hydroxylases enhance biodegradation of aromatic N-heterocycles. (3) Target sites for hydratation by an urocanase-like mechanism enhance biodegradation of imidazoles. Our complementary approach represents a feasible strategy for generating concrete rules for the prediction of biodegradability of organic compounds.

Integration of genomic medicine into pathology residency training: the stanford open curriculum.

PubMed

Schrijver, Iris; Natkunam, Yasodha; Galli, Stephen; Boyd, Scott D

2013-03-01

Next-generation sequencing methods provide an opportunity for molecular pathology laboratories to perform genomic testing that is far more comprehensive than single-gene analyses. Genome-based test results are expected to develop into an integral component of diagnostic clinical medicine and to provide the basis for individually tailored health care. To achieve these goals, rigorous interpretation of high-quality data must be informed by the medical history and the phenotype of the patient. The discipline of pathology is well positioned to implement genome-based testing and to interpret its results, but new knowledge and skills must be included in the training of pathologists to develop expertise in this area. Pathology residents should be trained in emerging technologies to integrate genomic test results appropriately with more traditional testing, to accelerate clinical studies using genomic data, and to help develop appropriate standards of data quality and evidence-based interpretation of these test results. We have created a genomic pathology curriculum as a first step in helping pathology residents build a foundation for the understanding of genomic medicine and its implications for clinical practice. This curriculum is freely accessible online. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Size Effects in Nanoscale Structural Phenomena

NASA Astrophysics Data System (ADS)

McElhinny, Kyle Matthew

The creation of nanostructures offers the opportunity to modify and tune properties in ways inaccessible in bulk materials. A key component in this development is the introduction of size effects which reduce the physical size, dimensionality, and increase the contribution of surface effects. The size effects strongly modify the structural dynamics in nanoscale systems and leads to changes in the vibrational, electrical, and optical properties. An increased level of understanding and control of nanoscale structural dynamics will enable more precise control over nanomaterial transport properties. My work has shown that 1D spatial confinement through the creation of semiconducting nanomembranes modifies the phonon population and dispersion. X ray thermal diffuse scattering distributions show an excess in intensity for nanomembranes less than 100 nm in thickness, for phonon modes with wavevectors spanning the entire Brillouin zone. This excess intensity indicates the development of new low energy phonon modes or the softening of elastic constants. Furthermore, an additional anisotropy in the phonon dispersion is observed with a symmetry matching the direction of spatial confinement. This work has also extended x ray thermal diffuse scattering for use in studying nanomaterials. In electro- and photoactive monolayers a structural reconfiguration can be produced by external optical stimuli. I have developed an electro and photoactive molecular monolayers on oxide surfaces. Using x ray reflectivity, I have evaluated the organization and reconfiguration of molecular monolayers deposited by Langmuir Blodgett technique. I have designed and probed the reconfiguration of optically reconfigurable monolayers of azobenzene donor molecules on semiconducting surfaces. These monolayers reconfigure through a cooperative switching process leading to the development of large isomeric domains. This work represents an advancement in the interpretation of x ray reflectivity from molecular monolayers and inhomogeneous surfaces. The growth 2D materials depends on the interactions between the substrate and the 2D material. I have studied the competition between kinetics and surface energetics which lead to a faceted Ge surface during the growth of Graphene nanoribbons. As part of this work, I have developed new methodologies for interpreting x ray reflectivity patterns from surfaces with multiple reflections. A systematic analysis of the temperature dependence of the faceting process indicates that the process is thermodynamically dominated at high temperatures.

Surface speciation of yttrium and neodymium sorbed on rutile: Interpretations using the change distribution model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ridley, Mora K.; Hiemstra, T; Machesky, Michael L.

2012-01-01

The adsorption of Y3+ and Nd3+ onto rutile has been evaluated over a wide range of pH (3 11) and surface loading conditions, as well as at two ionic strengths (0.03 and 0.3 m), and temperatures (25 and 50 C). The experimental results reveal the same adsorption behavior for the two trivalent ions onto the rutile surface, with Nd3+ first adsorbing at slightly lower pH values. The adsorption of both Y3+ and Nd3+ commences at pH values below the pHznpc of rutile. The experimental results were evaluated using a charge distribution (CD) and multisite complexation (MUSIC) model, and Basic Sternmore » layer description of the electric double layer (EDL). The coordination geometry of possible surface complexes were constrained by molecular-level information obtained from X-ray standing wave measurements and molecular dynamic (MD) simulation studies. X-ray standing wave measurements showed an inner-sphere tetradentate complex for Y3+ adsorption onto the (110) rutile surface (Zhang et al., 2004b). TheMDsimulation studies suggest additional bidentate complexes may form. The CD values for all surface species were calculated based on a bond valence interpretation of the surface complexes identified by X-ray and MD. The calculated CD values were corrected for the effect of dipole orientation of interfacial water. At low pH, the tetradentate complex provided excellent fits to the Y3+ and Nd3+ experimental data. The experimental and surface complexation modeling results show a strong pH dependence, and suggest that the tetradentate surface species hydrolyze with increasing pH. Furthermore, with increased surface loading of Y3+ on rutile the tetradentate binding mode was augmented by a hydrolyzed-bidentate Y3+ surface complex. Collectively, the experimental and surface complexation modeling results demonstrate that solution chemistry and surface loading impacts Y3+ surface speciation. The approach taken of incorporating molecular-scale information into surface complexation models (SCMs) should aid in elucidating a fundamental understating of ion-adsorption reactions.« less

Surface speciation of yttrium and neodymium sorbed on rutile: Interpretations using the charge distribution model

NASA Astrophysics Data System (ADS)

Ridley, Moira K.; Hiemstra, Tjisse; Machesky, Michael L.; Wesolowski, David J.; van Riemsdijk, Willem H.

2012-10-01

The adsorption of Y3+ and Nd3+ onto rutile has been evaluated over a wide range of pH (3-11) and surface loading conditions, as well as at two ionic strengths (0.03 and 0.3 m), and temperatures (25 and 50 °C). The experimental results reveal the same adsorption behavior for the two trivalent ions onto the rutile surface, with Nd3+ first adsorbing at slightly lower pH values. The adsorption of both Y3+ and Nd3+ commences at pH values below the pHznpc of rutile. The experimental results were evaluated using a charge distribution (CD) and multisite complexation (MUSIC) model, and Basic Stern layer description of the electric double layer (EDL). The coordination geometry of possible surface complexes were constrained by molecular-level information obtained from X-ray standing wave measurements and molecular dynamic (MD) simulation studies. X-ray standing wave measurements showed an inner-sphere tetradentate complex for Y3+ adsorption onto the (1 1 0) rutile surface (Zhang et al., 2004b). The MD simulation studies suggest additional bidentate complexes may form. The CD values for all surface species were calculated based on a bond valence interpretation of the surface complexes identified by X-ray and MD. The calculated CD values were corrected for the effect of dipole orientation of interfacial water. At low pH, the tetradentate complex provided excellent fits to the Y3+ and Nd3+ experimental data. The experimental and surface complexation modeling results show a strong pH dependence, and suggest that the tetradentate surface species hydrolyze with increasing pH. Furthermore, with increased surface loading of Y3+ on rutile the tetradentate binding mode was augmented by a hydrolyzed-bidentate Y3+ surface complex. Collectively, the experimental and surface complexation modeling results demonstrate that solution chemistry and surface loading impacts Y3+ surface speciation. The approach taken of incorporating molecular-scale information into surface complexation models (SCMs) should aid in elucidating a fundamental understating of ion-adsorption reactions.

Molecular relaxations, molecular orientation, and the friction characteristics of polyimide films. [wear characteristics of polymeric lubricant

NASA Technical Reports Server (NTRS)

Fusaro, R. L.

1975-01-01

The friction characteristics of polyimide films bonded to metallic substrates were studied from 25 to 500 C. These results were interpreted in terms of molecular orientation and thermomechanical data obtained by torsional braid analysis (TBA). A large friction transition was found to occur at 40 + or - 10 C in a dry argon atmosphere (10 ppm H2O). It was postulated that the mechanical stresses of sliding transform or reorder the molecules on the surface into a configuration conducive to easy shear, such as an extended chain. The molecular relaxation which occurs in this temperature region appears to give the molecules the necessary freedom for this reordering process to occur. The effects of velocity, reversibility, and thermal prehistory on the friction properties of polyimide were also studied.

Molecular relaxations, molecular orientation and the friction characteristics of polyimide films

NASA Technical Reports Server (NTRS)

Fusaro, R. L.

1975-01-01

The friction characteristics of polyimide films bonded to metallic substrates were studied from 25 to 500 C. These results were interpreted in terms of molecular orientation and thermomechanical data obtained by torsional braid analysis (TBA). A large friction transition was found to occur at 40 plus or minus 10 C in a dry argon atmosphere (10 ppm H2O). It was postulated that the mechanical stresses of sliding transform or reorder the molecules on the surface into a configuration conducive to easy shear, such as an extended chain. The molecular relaxation which occurs in this temperature region appears to give the molecules the necessary freedom for this reordering process to occur. The effects of velocity, reversibility, and thermal prehistory on the friction properties of polyimide were also studied.

Assessment of the level of agreement in the interpretation of plain radiographs of lumbar spondylosis among clinical physiotherapists in Ghana

PubMed Central

2014-01-01

Background Objective physical assessment of patients with lumbar spondylosis involves plain film radiographs (PFR) viewing and interpretation by the radiologists. Physiotherapists also routinely assess PFR within the scope of their practice. However, studies appraising the level of agreement of physiotherapists’ PFR interpretation with radiologists are not common in Ghana. Method Forty-one (41) physiotherapists took part in the cross-sectional survey. An assessment guide was developed from findings of the interpretation of three PFR of patients with lumbar spondylosis by a radiologist. The three PFR were selected from a pool of different radiographs based on clarity, common visible pathological features, coverage body segments and short post production period. Physiotherapists were required to view the same PFR after which they were assessed with the assessment guide according to the number of features identified correctly or incorrectly. The score range on the assessment form was 0–24, interpreted as follow: 0–8 points (low), 9–16 points (moderate) and 17–24 points (high) levels of agreement. Data were analyzed using one sample t-test and fisher’s exact test at α = 0.05. Results The mean score of interpretation for the physiotherapists was 12.7 ± 2.6 points compared to the radiologist’s interpretation of 24 points (assessment guide). The physiotherapists’ levels were found to be significantly associated with their academic qualification (p = 0.006) and sex (p = 0.001). However, their levels of agreement were not significantly associated with their age group (p = 0.098), work settings (p = 0.171), experience (p = 0.666), preferred PFR view (p = 0.088) and continuing education (p = 0.069). Conclusions The physiotherapists’ skills fall short of expectation for interpreting PFR of patients with lumbar spondylosis. The levels of agreement with radiologist’s interpretation have no link with year of clinial practice, age, work settings and continuing education. Thus, routine PFR viewing techniques should be made a priority in physiotherapists’ continuing professional education. PMID:24678695

The Role of Self-reports and Behavioral Measures of Interpretation Biases in Children with Varying Levels of Anxiety.

PubMed

Klein, Anke M; Flokstra, Emmelie; van Niekerk, Rianne; Klein, Steven; Rapee, Ronald M; Hudson, Jennifer L; Bögels, Susan M; Becker, Eni S; Rinck, Mike

2018-04-21

We investigated the role of self-reports and behavioral measures of interpretation biases and their content-specificity in children with varying levels of spider fear and/or social anxiety. In total, 141 selected children from a community sample completed an interpretation bias task with scenarios that were related to either spider threat or social threat. Specific interpretation biases were found; only spider-related interpretation bias and self-reported spider fear predicted unique variance in avoidance behavior on the Behavior Avoidance Task for spiders. Likewise, only social-threat related interpretation bias and self-reported social anxiety predicted anxiety during the Social Speech Task. These findings support the hypothesis that fearful children display cognitive biases that are specific to particular fear-relevant stimuli. Clinically, this insight might be used to improve treatments for anxious children by targeting content-specific interpretation biases related to individual disorders.

The use of Spanish language skills by physicians and nurses: policy implications for teaching and testing.

PubMed

Diamond, Lisa C; Tuot, Delphine S; Karliner, Leah S

2012-01-01

Language barriers present a substantial communication challenge in the hospital setting. To describe how clinicians with various levels of Spanish language proficiency work with interpreters or their own Spanish skills in common clinical scenarios. Survey of physicians and nurses who report ever speaking Spanish with patients on a general medicine hospital floor. Spanish proficiency rated on a 5-point scale, self-reported use of specific strategies (own Spanish skills, professional or ad-hoc interpreters) to overcome the language barrier. Sixty-eight physicians and 65 nurses participated. Physicians with low-level Spanish proficiency reported frequent use of ad-hoc interpreters for all information-based scenarios, except pre-rounding in the morning when most reported using their own Spanish skills. For difficult conversations and procedural consent, most used professional interpreters. Comparatively, physicians with medium proficiency reported higher rates of using their own Spanish skills for information-based scenarios, lower rates of professional interpreter use, and little use of ad-hoc interpreters. They rarely used their own Spanish skills or ad-hoc interpreters for difficult conversations. Physicians with high-level Spanish proficiency almost uniformly reported using their own Spanish skills. The majority (82%) of nurses had low-level Spanish proficiency, and frequently worked with professional interpreters for educating patients, but more often used ad hoc interpreters and their own Spanish skills for information-based scenarios, including medication administration. Physicians and nurses with limited Spanish proficiency use these skills, even in important clinical circumstances in the hospital. Health-care organizations should evaluate clinicians' non-English language proficiency and set policies about use of language skills in clinical care.

Reinventing the ames test as a quantitative lab that connects classical and molecular genetics.

PubMed

Goodson-Gregg, Nathan; De Stasio, Elizabeth A

2009-01-01

While many institutions use a version of the Ames test in the undergraduate genetics laboratory, students typically are not exposed to techniques or procedures beyond qualitative analysis of phenotypic reversion, thereby seriously limiting the scope of learning. We have extended the Ames test to include both quantitative analysis of reversion frequency and molecular analysis of revertant gene sequences. By giving students a role in designing their quantitative methods and analyses, students practice and apply quantitative skills. To help students connect classical and molecular genetic concepts and techniques, we report here procedures for characterizing the molecular lesions that confer a revertant phenotype. We suggest undertaking reversion of both missense and frameshift mutants to allow a more sophisticated molecular genetic analysis. These modifications and additions broaden the educational content of the traditional Ames test teaching laboratory, while simultaneously enhancing students' skills in experimental design, quantitative analysis, and data interpretation.

Kinematics of the Ultra-High-Velocity Gas in the Expanding Molecular Shell Adjacent to the W44 Supernova Remnant

NASA Astrophysics Data System (ADS)

Yamada, Masaya; Oka, Tomoharu; Tanaka, Kunihiko; Nomura, Mariko; Takekawa, Shunya; Iwata, Yuhei; Tokuyama, Sekito; Tanabe, Keisuke; Tsujimoto, Shiho; Furusawa, Maiko

2017-01-01

High-velocity compact cloud (HVCC) is a peculiar category of molecular clouds detected in the central molecular zone of our Galaxy (Oka et al. 1998, 2007, and 2012). They are characterized by compact appearances (d < 5 pc) and very large velocity widths (Δ V > 50 km s-1). Some of them show high CO J=3-2/J=1-0 intensity ratios (>= 1.5), indicating that they consist of dense and warm molecular gas. Dispite a number of efforts, we have not reached a comprehensive interpretation of HVCCs. Recently, we detected an extraordinaly broad velocity width feature, the `Bullet', in the molecular cloud interacting with the W44 supernova remnant. The Bullet shares essential properties with HVCCs. Because of its proximity, a close inspection of the Bullet must contribute to the understanding of HVCCs.

A Statistical Approach to Exoplanetary Molecular Spectroscopy Using Spitzer Eclipses

NASA Astrophysics Data System (ADS)

Deming, Drake; Garhart, Emily; Burrows, Adam; Fortney, Jonathan; Knutson, Heather; Todorov, Kamen

2018-01-01

Secondary eclipses of exoplanets observed using the Spitzer Space Telescope measure the total emission emergent from exoplanetary atmospheres integrated over broad photometric bands. Spitzer photometry is excellent for measuring day side temperatures, but is less well suited to the detection of molecular absorption or emission features. Even for very hot exoplanets, it can be difficult to attain the accuracy on eclipse depth that is needed to unambiguously interpret the Spitzer results in terms of molecular absorption or emission. However, a statistical approach, wherein we seek deviations from a simple blackbody planet as a function of the planet's equilibrium temperature, shows promise for defining the nature and strength of molecular absorption in ensembles of planets. In this paper, we explore such an approach using secondary eclipses observed for tens of hot exoplanets during Spitzer's Cycles 10, 12, and 13. We focus on the possibility that the hottest planets exhibit molecular features in emission, due to temperature inversions.

VAMPnets for deep learning of molecular kinetics.

PubMed

Mardt, Andreas; Pasquali, Luca; Wu, Hao; Noé, Frank

2018-01-02

There is an increasing demand for computing the relevant structures, equilibria, and long-timescale kinetics of biomolecular processes, such as protein-drug binding, from high-throughput molecular dynamics simulations. Current methods employ transformation of simulated coordinates into structural features, dimension reduction, clustering the dimension-reduced data, and estimation of a Markov state model or related model of the interconversion rates between molecular structures. This handcrafted approach demands a substantial amount of modeling expertise, as poor decisions at any step will lead to large modeling errors. Here we employ the variational approach for Markov processes (VAMP) to develop a deep learning framework for molecular kinetics using neural networks, dubbed VAMPnets. A VAMPnet encodes the entire mapping from molecular coordinates to Markov states, thus combining the whole data processing pipeline in a single end-to-end framework. Our method performs equally or better than state-of-the-art Markov modeling methods and provides easily interpretable few-state kinetic models.

Developmental Levels of Processing in Metaphor Interpretation.

ERIC Educational Resources Information Center

Johnson, Janice; Pascual-Leone, Juan

1989-01-01

Outlines a theory of metaphor that posits varying levels of semantic processing and formalizes the levels in terms of kinds of semantic mapping operators. Predicted complexity of semantic mapping operators was tested using metaphor interpretations of 204 children aged 6-12 years and 24 adults. Processing score increased predictably with age. (SAK)

Centering Effects in HLM Level-1 Predictor Variables.

ERIC Educational Resources Information Center

Schumacker, Randall E.; Bembry, Karen

Research has suggested that important research questions can be addressed with meaningful interpretations using hierarchical linear modeling (HLM). The proper interpretation of results, however, is invariably linked to the choice of centering for the Level-1 predictor variables that produce the outcome measure for the Level-2 regression analysis.…

Cued Speech Transliteration: Effects of Speaking Rate and Lag Time on Production Accuracy

ERIC Educational Resources Information Center

Krause, Jean C.; Tessler, Morgan P.

2016-01-01

Many deaf and hard-of-hearing children rely on interpreters to access classroom communication. Although the exact level of access provided by interpreters in these settings is unknown, it is likely to depend heavily on interpreter accuracy (portion of message correctly produced by the interpreter) and the factors that govern interpreter accuracy.…

Editor's Highlight: Genetic Targets of Acute Toluene Inhalation in Drosophila melanogaster

EPA Science Inventory

Interpretation and use of data from high-throughput assays for chemical toxicity require links between effects at molecular targets and adverse outcomes in whole animals. The well-characterized genome of Drosophila melanogaster provides a potential model system by which phenotypi...

Molecular docking and structural analysis of non-opioid analgesic drug acemetacin with halogen substitution: A DFT approach

NASA Astrophysics Data System (ADS)

Leenaraj, D. R.; Manimaran, D.; Joe, I. Hubert

2016-11-01

Acemetacin is a non-opioid analgesic which belongs to the class, the non-steroidal anti-inflammatory drug. The bioactive conformer was identified through potential energy surface scan studies. Spectral features of acemetacin have been probed by the techniques of Fourier transform infrared, Raman and Nuclear magnetic resonance combined with density functional theory calculations at the B3LYP level with 6-311 + G(d,p) basis set. The detailed interpretation of vibrational spectral assignments has been carried out on the basis of potential energy distribution method. Geometrical parameters reveal that the carbonyl substitution in between chlorophenyl and indole ring leads to a significant loss of planarity. The red-shifted Cdbnd O stretching wavenumber describe the conjugation between N and O atoms. The shifted Csbnd H stretching wavenumbers of Osbnd CH3 and Osbnd CH2 groups depict the back-donation and induction effects. The substitution of halogen atoms on the title molecule influences the charge distribution and the geometrical parameters. Drug activity and binding affinity of halogen substitution in title molecule with target protein were undertaken by molecular docking study. This study enlightens the effects of bioefficiency due to the halogen substitution in the molecule.

Combining animal personalities with transcriptomics resolves individual variation within a wild-type zebrafish population and identifies underpinning molecular differences in brain function.

PubMed

Rey, S; Boltana, S; Vargas, R; Roher, N; Mackenzie, S

2013-12-01

Resolving phenotype variation within a population in response to environmental perturbation is central to understanding biological adaptation. Relating meaningful adaptive changes at the level of the transcriptome requires the identification of processes that have a functional significance for the individual. This remains a major objective towards understanding the complex interactions between environmental demand and an individual's capacity to respond to such demands. The interpretation of such interactions and the significance of biological variation between individuals from the same or different populations remain a difficult and under-addressed question. Here, we provide evidence that variation in gene expression between individuals in a zebrafish population can be partially resolved by a priori screening for animal personality and accounts for >9% of observed variation in the brain transcriptome. Proactive and reactive individuals within a wild-type population exhibit consistent behavioural responses over time and context that relates to underlying differences in regulated gene networks and predicted protein-protein interactions. These differences can be mapped to distinct regions of the brain and provide a foundation towards understanding the coordination of underpinning adaptive molecular events within populations. © 2013 John Wiley & Sons Ltd.

Effect of glass fiber surface treatments on mechanical strength of epoxy based composite materials.

PubMed

Iglesias, J G; González-Benito, J; Aznar, A J; Bravo, J; Baselga, J

2002-06-01

Sizing glass fibers with silane coupling agents enhances the adhesion and the durability of the fiber/polymer matrix interface in composite materials. There are several tests to determine the interfacial strength between a fiber and resin, but all of them present difficulties in interpreting the results and/or sample preparation. In this study, we observed the influence of different aminosilanes fiber coatings on the resistance of epoxy-based composite materials using a very easy fractographic test. In addition, we tried a new fluorescence method to get information on a molecular level precisely at the interface. Strength was taken into account from two standpoints: (i) mechanical strength and (ii) the resistance to hydrolysis of the interface in oriented glass-reinforced epoxy-based composites. Three silanes: gamma-aminopropyltriethoxysilane, gamma-Aminopropylmethyldiethoxysilane, and gamma-Aminopropyldimethylethoxysilane were used to obtain different molecular structures at the interface. It was concluded that: (i) the more accessible amine groups are, the higher the interface rigidity is; (ii) an interpenetrating network mechanism seems to be the most important for adhesion and therefore to the interfacial strength; and (iii) the higher the degree of crosslinking in the silane coupling layer is, the higher the hydrolytic damage rate is.

Computational Amide I Spectroscopy for Refinement of Disordered Peptide Ensembles: Maximum Entropy and Related Approaches

NASA Astrophysics Data System (ADS)

Reppert, Michael; Tokmakoff, Andrei

The structural characterization of intrinsically disordered peptides (IDPs) presents a challenging biophysical problem. Extreme heterogeneity and rapid conformational interconversion make traditional methods difficult to interpret. Due to its ultrafast (ps) shutter speed, Amide I vibrational spectroscopy has received considerable interest as a novel technique to probe IDP structure and dynamics. Historically, Amide I spectroscopy has been limited to delivering global secondary structural information. More recently, however, the method has been adapted to study structure at the local level through incorporation of isotope labels into the protein backbone at specific amide bonds. Thanks to the acute sensitivity of Amide I frequencies to local electrostatic interactions-particularly hydrogen bonds-spectroscopic data on isotope labeled residues directly reports on local peptide conformation. Quantitative information can be extracted using electrostatic frequency maps which translate molecular dynamics trajectories into Amide I spectra for comparison with experiment. Here we present our recent efforts in the development of a rigorous approach to incorporating Amide I spectroscopic restraints into refined molecular dynamics structural ensembles using maximum entropy and related approaches. By combining force field predictions with experimental spectroscopic data, we construct refined structural ensembles for a family of short, strongly disordered, elastin-like peptides in aqueous solution.

Electrostatics-mediated α-chymotrypsin inhibition by functionalized single-walled carbon nanotubes.

PubMed

Zhao, Daohui; Zhou, Jian

2017-01-04

The α-chymotrypsin (α-ChT) enzyme is extensively used for studying nanomaterial-induced enzymatic activity inhibition. A recent experimental study reported that carboxylized carbon nanotubes (CNTs) played an important role in regulating the α-ChT activity. In this study, parallel tempering Monte Carlo and molecular dynamics simulations were combined to elucidate the interactions between α-ChT and CNTs in relation to the CNT functional group density. The simulation results indicate that the adsorption and the driving force of α-ChT on different CNTs are contingent on the carboxyl density. Meanwhile, minor secondary structural changes are observed in adsorption processes. It is revealed that α-ChT interacts with pristine CNTs through hydrophobic forces and exhibits a non-competitive characteristic with the active site facing towards the solution; while it binds to carboxylized CNTs with the active pocket through a dominant electrostatic association, which causes enzymatic activity inhibition in a competitive-like mode. These findings are in line with experimental results, and well interpret the activity inhibition of α-ChT at the molecular level. Moreover, this study would shed light on the detailed mechanism of specific recognition and regulation of α-ChT by other functionalized nanomaterials.

Sulfurized carbohydrates: an important sedimentary sink for organic carbon?

NASA Astrophysics Data System (ADS)

Sinninghe Damsté, Jaap S.; Kok, Marika D.; Köster, Jürgen; Schouten, Stefan

1998-12-01

In contrast to the general belief that carbohydrate carbon (C CHO) is preferentially degraded and is not extensively preserved in the sedimentary record, it is shown here that C CHO forms a large fraction of the organic matter (OM) of the total organic carbon (TOC)-rich upper Jurassic Kimmeridge Clay Formation as a result of early diagenetic sulfurization, a previously unrecognized pathway of OM preservation. This is evident from both changes in the molecular composition of the insoluble OM and from δ 13C TOC shifts of 6‰ with varying C CHO contents. Furthermore, experiments simulating the natural sulfurization of the C CHO-rich alga Phaeocystis spp. demonstrated that sulfurization can indeed lead to a substantial preservation of C CHO with a molecular fingerprint identical to that of the Kimmeridge Clay and many other Recent and ancient marine OM-rich sediments. These results imply that preservation of C CHO can exert a fundamental control on δ 13C TOC in OM-rich sediments, complicating the interpretation of δ 13C TOC records with regard to estimating terrestrial versus aquatic OM fractions, reconstruction of past atmospheric CO 2 levels and global carbon budget models.

Molecular threading and tunable molecular recognition on DNA origami nanostructures.

PubMed

Wu, Na; Czajkowsky, Daniel M; Zhang, Jinjin; Qu, Jianxun; Ye, Ming; Zeng, Dongdong; Zhou, Xingfei; Hu, Jun; Shao, Zhifeng; Li, Bin; Fan, Chunhai

2013-08-21

The DNA origami technology holds great promise for the assembly of nanoscopic technological devices and studies of biochemical reactions at the single-molecule level. For these, it is essential to establish well controlled attachment of functional materials to predefined sites on the DNA origami nanostructures for reliable measurements and versatile applications. However, the two-sided nature of the origami scaffold has shown limitations in this regard. We hypothesized that holes of the commonly used two-dimensional DNA origami designs are large enough for the passage of single-stranded (ss)-DNA. Sufficiently long ssDNA initially located on one side of the origami should thus be able to "thread" to the other side through the holes in the origami sheet. By using an origami sheet attached with patterned biotinylated ssDNA spacers and monitoring streptavidin binding with atomic force microscopic (AFM) imaging, we provide unambiguous evidence that the biotin ligands positioned on one side have indeed threaded through to the other side. Our finding reveals a previously overlooked critical design feature that should provide new interpretations to previous experiments and new opportunities for the construction of origami structures with new functional capabilities.

Physico-chemical studies of the experimental and theoretical properties of organic nonlinear optical material 4-chloro-4'methoxy benzylideneaniline

NASA Astrophysics Data System (ADS)

George, Merin; John, Nimmy L.; Saravana Kumar, M.; Subashini, A.; Sajan, D.

2017-01-01

The FT-IR, FT-Raman and UV-visible spectral analysis of 4-chloro 4'-methoxy benzylidene aniline were done experimentally and interpreted with the aid of normal coordinate analysis based on density functional theory (DFT) at the B3LYP/6-311++G (d, p) level of theory. Natural Bond orbital analysis was performed to understand the charge transfer interactions and reactive sites within the system. HOMO-LUMO analysis and first static and dynamic hyperpolarizability calculations were carried out in order to confirm the NLO activity of CMOBA. Photophysical characterization was done to understand the fluorescence emission and lifetime of CMOBA leading to application in blue OLEDs. The Molecular Electrostatic Potential Map was simulated to identify the active sites for electrophilic and nucleophilic attack or the active sites of the molecule which can bind to proteins. Molecular docking analysis revealed its potential as an inhibitor for different proteins which are responsible for cancer and many inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease and psoriasis. Experimental studies of invitro antiproliferative effect by MTT assay verified the anticancer properties of CMOBA.

Decoding the mechanical fingerprints of biomolecules.

PubMed

Dudko, Olga K

2016-01-01

The capacity of biological macromolecules to act as exceedingly sophisticated and highly efficient cellular machines - switches, assembly factors, pumps, or motors - is realized through their conformational transitions, that is, their folding into distinct shapes and selective binding to other molecules. Conformational transitions can be induced, monitored, and manipulated by pulling individual macromolecules apart with an applied force. Pulling experiments reveal, for a given biomolecule, the relationship between applied force and molecular extension. Distinct signatures in the force-extension relationship identify a given biomolecule and thus serve as the molecule's 'mechanical fingerprints'. But, how can these fingerprints be decoded to uncover the energy barriers crossed by the molecule in the course of its conformational transition, as well as the associated timescales? This review summarizes a powerful class of approaches to interpreting single-molecule force spectroscopy measurements - namely, analytically tractable approaches. On the fundamental side, analytical theories have the power to reveal the unifying principles underneath the bewildering diversity of biomolecules and their behaviors. On the practical side, analytical expressions that result from these theories are particularly well suited for a direct fit to experimental data, yielding the important parameters that govern biological processes at the molecular level.

Investigation of the linear and second-order nonlinear optical properties of molecular crystals within the local field theory.

PubMed

Seidler, Tomasz; Stadnicka, Katarzyna; Champagne, Benoît

2013-09-21

In this paper it is shown that modest calculations combining first principles evaluations of the molecular properties with electrostatic interaction schemes to account for the crystal environment effects are reliable for predicting and interpreting the experimentally measured electric linear and second-order nonlinear optical susceptibilities of molecular crystals within the experimental error bars. This is illustrated by considering two molecular crystals, namely: 2-methyl-4-nitroaniline and 4-(N,N-dimethylamino)-3-acetamidonitrobenzene. Three types of surrounding effects should be accounted for (i) the polarization due to the surrounding molecules, described here by static electric fields originating from their electric dipoles or charge distributions, (ii) the intermolecular interactions, which affect the geometry and particularly the molecular conformation, and (iii) the screening of the external electric field by the constitutive molecules. This study further highlights the role of electron correlation on the linear and nonlinear responses of molecular crystals and the challenge of describing frequency dispersion.

Studies on molecular structure, vibrational spectra and molecular docking analysis of 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate.

PubMed

Suresh, D M; Amalanathan, M; Joe, I Hubert; Jothy, V Bena; Diao, Yun-Peng

2014-09-15

The molecular structure, vibrational analysis and molecular docking analysis of the 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate (MDDNAB) molecule have been carried out using FT-IR and FT-Raman spectroscopic techniques and DFT method. The equilibrium geometry, harmonic vibrational wave numbers, various bonding features have been computed using density functional method. The calculated molecular geometry has been compared with experimental data. The detailed interpretation of the vibrational spectra has been carried out by using VEDA program. The hyper-conjugative interactions and charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The simulated FT-IR and FT-Raman spectra satisfactorily coincide with the experimental spectra. The PES and charge analysis have been made. The molecular docking was done to identify the binding energy and the Hydrogen bonding with the cancer protein molecule. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular approaches for classifying endometrial carcinoma.

PubMed

Piulats, Josep M; Guerra, Esther; Gil-Martín, Marta; Roman-Canal, Berta; Gatius, Sonia; Sanz-Pamplona, Rebeca; Velasco, Ana; Vidal, August; Matias-Guiu, Xavier

2017-04-01

Endometrial carcinoma is the most common cancer of the female genital tract. This review article discusses the usefulness of molecular techniques to classify endometrial carcinoma. Any proposal for molecular classification of neoplasms should integrate morphological features of the tumors. For that reason, we start with the current histological classification of endometrial carcinoma, by discussing the correlation between genotype and phenotype, and the most significant recent improvements. Then, we comment on some of the possible flaws of this classification, by discussing also the value of molecular pathology in improving them, including interobserver variation in pathologic interpretation of high grade tumors. Third, we discuss the importance of applying TCGA molecular approach to clinical practice. We also comment on the impact of intratumor heterogeneity in classification, and finally, we will discuss briefly, the usefulness of TCGA classification in tailoring immunotherapy in endometrial cancer patients. We suggest combining pathologic classification and the surrogate TCGA molecular classification for high-grade endometrial carcinomas, as an option to improve assessment of prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative estimation of pesticide-likeness for agrochemical discovery.

PubMed

Avram, Sorin; Funar-Timofei, Simona; Borota, Ana; Chennamaneni, Sridhar Rao; Manchala, Anil Kumar; Muresan, Sorel

2014-12-01

The design of chemical libraries, an early step in agrochemical discovery programs, is frequently addressed by means of qualitative physicochemical and/or topological rule-based methods. The aim of this study is to develop quantitative estimates of herbicide- (QEH), insecticide- (QEI), fungicide- (QEF), and, finally, pesticide-likeness (QEP). In the assessment of these definitions, we relied on the concept of desirability functions. We found a simple function, shared by the three classes of pesticides, parameterized particularly, for six, easy to compute, independent and interpretable, molecular properties: molecular weight, logP, number of hydrogen bond acceptors, number of hydrogen bond donors, number of rotatable bounds and number of aromatic rings. Subsequently, we describe the scoring of each pesticide class by the corresponding quantitative estimate. In a comparative study, we assessed the performance of the scoring functions using extensive datasets of patented pesticides. The hereby-established quantitative assessment has the ability to rank compounds whether they fail well-established pesticide-likeness rules or not, and offer an efficient way to prioritize (class-specific) pesticides. These findings are valuable for the efficient estimation of pesticide-likeness of vast chemical libraries in the field of agrochemical discovery. Graphical AbstractQuantitative models for pesticide-likeness were derived using the concept of desirability functions parameterized for six, easy to compute, independent and interpretable, molecular properties: molecular weight, logP, number of hydrogen bond acceptors, number of hydrogen bond donors, number of rotatable bounds and number of aromatic rings.

Simulation of spin label structure and its implication in molecular characterization

PubMed Central

Fajer, Piotr; Fajer, Mikolai; Zawrotny, Michael; Yang, Wei

2016-01-01

Interpretation of EPR from spin labels in terms of structure and dynamics requires knowledge of label behavior. General strategies were developed for simulation of labels used in EPR of proteins. The criteria for those simulations are: (a) exhaustive sampling of rotamer space; (b) consensus of results independent of starting points; (c) inclusion of entropy. These criteria are satisfied only when the number of transitions in any dihedral angle exceeds 100 and the simulation maintains thermodynamic equilibrium. Methods such as conventional MD do not efficiently cross energetic barriers, Simulated Annealing, Monte Carlo or popular Rotamer Library methodologies are potential energy based and ignore entropy (in addition to their specific shortcomings: environment fluctuations, fixed environment or electrostatics). Simulated Scaling method, avoids above flaws by modulating the forcefields between 0 (allowing crossing energy barriers) and full potential (sampling minima). Spin label diffuses on this surface while remaining in thermodynamic equilibrium. Simulations show that: (a) single conformation is rare, often there are 2–4 populated rotamers; (b) position of the NO varies up to 16Å. These results illustrate necessity for caution when interpreting EPR signals in terms of molecular structure. For example the 10–16Å distance change in DEER should not be interpreted as a large conformational change, it can well be a flip about Cα -Cβ bond. Rigorous exploration of possible rotamer structures of a spin label is paramount in signal interpretation. We advocate use of bifunctional labels, which motion is restricted 10,000-fold and the NO position is restricted to 2–5Å. PMID:26478501

Fluorescence of molecular hydrogen excited by solar extreme-ultraviolet radiation

NASA Technical Reports Server (NTRS)

Feldman, P. D.; Fastie, W. G.

1973-01-01

During trans-earth coast, the Apollo 17 ultraviolet spectrometer was scheduled to make observations of the far ultraviolet background in selected regions of the sky. In the course of one of these observations, the spacecraft fuel cells were routinely purged of excess hydrogen and water vapor. The ultraviolet fluorescence spectrum of the purged molecular hydrogen excited by solar extreme ultraviolet radiation is interpreted by absorption of solar L-beta and L-gamma radiation in the nearly resonant (6, 0) and (11, 0) Lyman bands. The results are deemed significant for ultraviolet spectroscopic investigations of the atmospheres of the moon and planets since Lyman-band fluorescence provides an unambiguous means of identification of molecular hydrogen in upper atmospheres.

Localized diffusive motion on two different time scales in solid alkane nanoparticles

NASA Astrophysics Data System (ADS)

Wang, S.-K.; Mamontov, E.; Bai, M.; Hansen, F. Y.; Taub, H.; Copley, J. R. D.; García Sakai, V.; Gasparovic, G.; Jenkins, T.; Tyagi, M.; Herwig, K. W.; Neumann, D. A.; Montfrooij, W.; Volkmann, U. G.

2010-09-01

High-energy-resolution quasielastic neutron scattering on three complementary spectrometers has been used to investigate molecular diffusive motion in solid nano- to bulk-sized particles of the alkane n-C32H66. The crystalline-to-plastic and plastic-to-fluid phase transition temperatures are observed to decrease as the particle size decreases. In all samples, localized molecular diffusive motion in the plastic phase occurs on two different time scales: a "fast" motion corresponding to uniaxial rotation about the long molecular axis; and a "slow" motion attributed to conformational changes of the molecule. Contrary to the conventional interpretation in bulk alkanes, the fast uniaxial rotation begins in the low-temperature crystalline phase.

Differential Decay of Human Faecal Bacteroides in Marine and Freshwater

EPA Science Inventory

Gene sequences from Bacteroides and relatives are being considered for the enumeration of aquatic fecal contamination and estimation of public health risk. To interpret these data, it is necessary to understand the decay of molecular and cultivated indicators and pathogens in en...

Generic interpreters and microprocessor verification

NASA Technical Reports Server (NTRS)

Windley, Phillip J.

1990-01-01

The following topics are covered in viewgraph form: (1) generic interpreters; (2) Viper microprocessors; (3) microprocessor verification; (4) determining correctness; (5) hierarchical decomposition; (6) interpreter theory; (7) AVM-1; (8) phase-level specification; and future work.

Molecular structures and intramolecular dynamics of pentahalides

NASA Astrophysics Data System (ADS)

Ischenko, A. A.

2017-03-01

This paper reviews advances of modern gas electron diffraction (GED) method combined with high-resolution spectroscopy and quantum chemical calculations in studies of the impact of intramolecular dynamics in free molecules of pentahalides. Some recently developed approaches to the electron diffraction data interpretation, based on direct incorporation of the adiabatic potential energy surface parameters to the diffraction intensity are described. In this way, complementary data of different experimental and computational methods can be directly combined for solving problems of the molecular structure and its dynamics. The possibility to evaluate some important parameters of the adiabatic potential energy surface - barriers to pseudorotation and saddle point of intermediate configuration from diffraction intensities in solving the inverse GED problem is demonstrated on several examples. With increasing accuracy of the electron diffraction intensities and the development of the theoretical background of electron scattering and data interpretation, it has become possible to investigate complex nuclear dynamics in fluxional systems by the GED method. Results of other research groups are also included in the discussion.

Thermodynamic and structural effect of urea and guanidine chloride on the helical and on a hairpin fragment of GB1 from molecular simulations.

PubMed

Meloni, R; Tiana, G

2017-04-01

With the help of molecular-dynamics simulations, we studied the effect of urea and guanidine chloride on the thermodynamic and structural properties of the helical fragment of protein GB1, comparing them with those of its second beta hairpin. We showed that the helical fragment in different solvents populates an ensemble of states that is more complex than that of the hairpin, and thus the associated experimental observables (circular-dichroism spectra, secondary chemical shifts, m values), that we back-calculated from the simulations and compared with the actual data, are more difficult to interpret. We observed that in the case of both peptides, urea binds tightly to their backbone, while guanidine exerts its denaturing effect in a more subtle way, strongly affecting the electrostatic properties of the solution. This difference can have consequences in the way denaturation experiments are interpreted. Proteins 2017; 85:753-763. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

MelanomaDB: A Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

PubMed Central

Trevarton, Alexander J.; Mann, Michael B.; Knapp, Christoph; Araki, Hiromitsu; Wren, Jonathan D.; Stones-Havas, Steven; Black, Michael A.; Print, Cristin G.

2013-01-01

Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g., mutations) in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability, and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html. A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research. The MelanomaDB database illustrates dysregulation of specific signaling pathways across 310 exome-sequenced melanomas and in individual tumors and identifies the distribution of somatic variants in melanoma. We suggest that MelanomaDB can provide a context in which to interpret the tumor molecular profiles of individual melanoma patients relative to biological information and available drug therapies. PMID:23875173

Analyzing Single-Molecule Time Series via Nonparametric Bayesian Inference

PubMed Central

Hines, Keegan E.; Bankston, John R.; Aldrich, Richard W.

2015-01-01

The ability to measure the properties of proteins at the single-molecule level offers an unparalleled glimpse into biological systems at the molecular scale. The interpretation of single-molecule time series has often been rooted in statistical mechanics and the theory of Markov processes. While existing analysis methods have been useful, they are not without significant limitations including problems of model selection and parameter nonidentifiability. To address these challenges, we introduce the use of nonparametric Bayesian inference for the analysis of single-molecule time series. These methods provide a flexible way to extract structure from data instead of assuming models beforehand. We demonstrate these methods with applications to several diverse settings in single-molecule biophysics. This approach provides a well-constrained and rigorously grounded method for determining the number of biophysical states underlying single-molecule data. PMID:25650922

Tools for the functional interpretation of metabolomic experiments.

PubMed

Chagoyen, Monica; Pazos, Florencio

2013-11-01

The so-called 'omics' approaches used in modern biology aim at massively characterizing the molecular repertories of living systems at different levels. Metabolomics is one of the last additions to the 'omics' family and it deals with the characterization of the set of metabolites in a given biological system. As metabolomic techniques become more massive and allow characterizing larger sets of metabolites, automatic methods for analyzing these sets in order to obtain meaningful biological information are required. Only recently the first tools specifically designed for this task in metabolomics appeared. They are based on approaches previously used in transcriptomics and other 'omics', such as annotation enrichment analysis. These, together with generic tools for metabolic analysis and visualization not specifically designed for metabolomics will for sure be in the toolbox of the researches doing metabolomic experiments in the near future.

Origins and modeling of many-body exchange effects in van der Waals clusters

NASA Astrophysics Data System (ADS)

Chałasiński, Grzegorz; Rak, Janusz; Szcześniak, Małgorzata M.; Cybulski, sławomir M.

1997-02-01

We analyze the many-body exchange interactions in atomic and molecular clusters as they arise in the supermolecular SCF and MP2 approaches. A rigorous formal setting is provided by the symmetry-adapted perturbation theory. Particular emphasis is put on the decomposition into the single exchange (SE) and triple exchange (TE) terms, at the SCF and correlated levels. We also propose a novel approach, whereby selected SE nonadditive exchange terms are evaluated indirectly, as differences of the two-body SAPT corrections arising between the components of the trimer treated as a complex of a dimer and a monomer (pseudodimer approach). This provides additional insights into the nature of various nonadditive effects, an interpretation of supermolecular interaction energies, and may serve as a viable alternative for the calculation of some SE terms.

Population trapping in the excited states using vacuum-induced coherence and adiabatic process

NASA Astrophysics Data System (ADS)

Lal Kumawat, Babu; Kumar, Pardeep; Dasgupta, Shubhrangshu

2018-02-01

We theoretically investigate how population can be trapped in the closely spaced excited levels in presence of vacuum-induced coherence (VIC). We employ delayed pulses to transfer population from a meta-stable state to the excited states. Subsequently, spontaneous emission from these excited states builds coherence between them. This coherence can be probed by using chirping, which leads to the decoupling of the excited states from the ground state thereby ensuring population transfer via delayed pulses. Our results indicate that the existence of VIC leads to the generation of a mixed state in the excited state manifold, where trapping of the population occurs even in the presence of large decay. This trapping may be realized in molecular systems and can be interpreted as a sensitive probe of VIC. We present suitable numerical analysis to support our results.

Clonality Testing in Veterinary Medicine: A Review With Diagnostic Guidelines.

PubMed

Keller, S M; Vernau, W; Moore, P F

2016-07-01

The accurate distinction of reactive and neoplastic lymphoid proliferations can present challenges. Given the different prognoses and treatment strategies, a correct diagnosis is crucial. Molecular clonality assays assess rearranged lymphocyte antigen receptor gene diversity and can help differentiate reactive from neoplastic lymphoid proliferations. Molecular clonality assays are commonly used to assess atypical, mixed, or mature lymphoid proliferations; small tissue fragments that lack architecture; and fluid samples. In addition, clonality testing can be utilized to track neoplastic clones over time or across anatomic sites. Molecular clonality assays are not stand-alone tests but useful adjuncts that follow clinical, morphologic, and immunophenotypic assessment. Even though clonality testing provides valuable information in a variety of situations, the complexities and pitfalls of this method, as well as its dependency on the experience of the interpreter, are often understated. In addition, a lack of standardized terminology, laboratory practices, and interpretational guidelines hinders the reproducibility of clonality testing across laboratories in veterinary medicine. The objectives of this review are twofold. First, the review is intended to familiarize the diagnostic pathologist or interested clinician with the concepts, potential pitfalls, and limitations of clonality testing. Second, the review strives to provide a basis for future harmonization of clonality testing in veterinary medicine by providing diagnostic guidelines. © The Author(s) 2016.

Altered apolipoprotein C expression in association with cognition impairments and hippocampus volume in schizophrenia and bipolar disorder.

PubMed

Knöchel, Christian; Kniep, Jonathan; Cooper, Jason D; Stäblein, Michael; Wenzler, Sofia; Sarlon, Jan; Prvulovic, David; Linden, David E J; Bahn, Sabine; Stocki, Pawel; Ozcan, Sureyya; Alves, Gilberto; Carvalho, Andre F; Reif, Andreas; Oertel-Knöchel, Viola

2017-04-01

Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders.

Docking-based modeling of protein-protein interfaces for extensive structural and functional characterization of missense mutations.

PubMed

Barradas-Bautista, Didier; Fernández-Recio, Juan

2017-01-01

Next-generation sequencing (NGS) technologies are providing genomic information for an increasing number of healthy individuals and patient populations. In the context of the large amount of generated genomic data that is being generated, understanding the effect of disease-related mutations at molecular level can contribute to close the gap between genotype and phenotype and thus improve prevention, diagnosis or treatment of a pathological condition. In order to fully characterize the effect of a pathological mutation and have useful information for prediction purposes, it is important first to identify whether the mutation is located at a protein-binding interface, and second to understand the effect on the binding affinity of the affected interaction/s. Computational methods, such as protein docking are currently used to complement experimental efforts and could help to build the human structural interactome. Here we have extended the original pyDockNIP method to predict the location of disease-associated nsSNPs at protein-protein interfaces, when there is no available structure for the protein-protein complex. We have applied this approach to the pathological interaction networks of six diseases with low structural data on PPIs. This approach can almost double the number of nsSNPs that can be characterized and identify edgetic effects in many nsSNPs that were previously unknown. This can help to annotate and interpret genomic data from large-scale population studies, and to achieve a better understanding of disease at molecular level.

Docking-based modeling of protein-protein interfaces for extensive structural and functional characterization of missense mutations

PubMed Central

2017-01-01

Next-generation sequencing (NGS) technologies are providing genomic information for an increasing number of healthy individuals and patient populations. In the context of the large amount of generated genomic data that is being generated, understanding the effect of disease-related mutations at molecular level can contribute to close the gap between genotype and phenotype and thus improve prevention, diagnosis or treatment of a pathological condition. In order to fully characterize the effect of a pathological mutation and have useful information for prediction purposes, it is important first to identify whether the mutation is located at a protein-binding interface, and second to understand the effect on the binding affinity of the affected interaction/s. Computational methods, such as protein docking are currently used to complement experimental efforts and could help to build the human structural interactome. Here we have extended the original pyDockNIP method to predict the location of disease-associated nsSNPs at protein-protein interfaces, when there is no available structure for the protein-protein complex. We have applied this approach to the pathological interaction networks of six diseases with low structural data on PPIs. This approach can almost double the number of nsSNPs that can be characterized and identify edgetic effects in many nsSNPs that were previously unknown. This can help to annotate and interpret genomic data from large-scale population studies, and to achieve a better understanding of disease at molecular level. PMID:28841721

Saturn’s gravitational field induced by its equatorially antisymmetric zonal winds

NASA Astrophysics Data System (ADS)

Kong, Dali; Zhang, Keke; Schubert, Gerald; Anderson, John D.

2018-05-01

The cloud-level zonal winds of Saturn are marked by a substantial equatorially antisymmetric component with a speed of about 50ms‑1 which, if they are sufficiently deep, can produce measurable odd zonal gravitational coefficients ΔJ 2k+1, k = 1, 2, 3, 4. This study, based on solutions of the thermal-gravitational wind equation, provides a theoretical basis for interpreting the odd gravitational coefficients of Saturn in terms of its equatorially antisymmetric zonal flow. We adopt a Saturnian model comprising an ice-rock core, a metallic dynamo region and an outer molecular envelope. We use an equatorially antisymmetric zonal flow that is parameterized, confined in the molecular envelope and satisfies the solvability condition required for the thermal-gravitational wind equation. The structure and amplitude of the zonal flow at the cloud level are chosen to be consistent with observations of Saturn. We calculate the odd zonal gravitational coefficients ΔJ 2k+1, k = 1, 2, 3, 4 by regarding the depth of the equatorially antisymmetric winds as a parameter. It is found that ΔJ 3 is ‑4.197 × 10‑8 if the zonal winds extend about 13 000 km downward from the cloud tops while it is ‑0.765 × 10‑8 if the depth is about 4000 km. The depth/profile of the equatorially antisymmetric zonal winds can eventually be estimated when the high-precision measurements of the Cassini Grand Finale become available.

State of the art and new developments in molecular diagnostics for hemoglobinopathies in multiethnic societies.

PubMed

Harteveld, C L

2014-02-01

For detecting carriers of thalassemia traits, the basic part of diagnostics consists of measurement of the hematological indices followed by mostly automatic separation and measurement of the Hb fractions, while direct Hb separation either on high pressure liquid chromatography or capillary electrophoresis is sufficient to putatively identify carriers of the common Hb variants like HbS, C, E, D, and O-Arab. A putative positive result is reported together with an advice for parents, partner, or family analysis. For couples, presumed at-risk confirmation at the DNA level is essential. In general, this part of diagnostics is done in specialized centers provided with sufficient experience and the technical tools needed to combine hematological and biochemical interpretation with identification of the mutations at the molecular level. State-of-the-art tools are usually available in centers that also provide prenatal diagnosis and should consist of gap-PCR for the common deletions, direct DNA sequencing for all kind of point-mutations and the capacity to uncover novel or rare mutations or disease mechanisms. New developments are MLPA for large and eventually unknown deletion defects and microarray technology for fine mapping and primer design for breakpoint analysis. Gap-PCR primers designed in the region flanking the deletion breakpoints can subsequently be used to facilitate carrier detection of uncommon deletions in family members or isolated populations in laboratories where no microarray technology or MLPA is available. © 2013 John Wiley & Sons Ltd.

Deciphering Multifactorial Resistance Phenotypes in Acinetobacter baumannii by Genomics and Targeted Label-free Proteomics.

PubMed

Cecchini, Tiphaine; Yoon, Eun-Jeong; Charretier, Yannick; Bardet, Chloé; Beaulieu, Corinne; Lacoux, Xavier; Docquier, Jean-Denis; Lemoine, Jerome; Courvalin, Patrice; Grillot-Courvalin, Catherine; Charrier, Jean-Philippe

2018-03-01

Resistance to β-lactams in Acinetobacter baumannii involves various mechanisms. To decipher them, whole genome sequencing (WGS) and real-time quantitative polymerase chain reaction (RT-qPCR) were complemented by mass spectrometry (MS) in selected reaction monitoring mode (SRM) in 39 clinical isolates. The targeted label-free proteomic approach enabled, in one hour and using a single method, the quantitative detection of 16 proteins associated with antibiotic resistance: eight acquired β-lactamases ( i.e. GES, NDM-1, OXA-23, OXA-24, OXA-58, PER, TEM-1, and VEB), two resident β-lactamases ( i.e. ADC and OXA-51-like) and six components of the two major efflux systems ( i.e. AdeABC and AdeIJK). Results were normalized using "bacterial quantotypic peptides," i.e. peptide markers of the bacterial quantity, to obtain precise protein quantitation (on average 8.93% coefficient of variation for three biological replicates). This allowed to correlate the levels of resistance to β-lactam with those of the production of acquired as well as resident β-lactamases or of efflux systems. SRM detected enhanced ADC or OXA-51-like production and absence or increased efflux pump production. Precise protein quantitation was particularly valuable to detect resistance mechanisms mediated by regulated genes or by overexpression of chromosomal genes. Combination of WGS and MS, two orthogonal and complementary techniques, allows thereby interpretation of the resistance phenotypes at the molecular level. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Theory of attosecond delays in molecular photoionization.

PubMed

Baykusheva, Denitsa; Wörner, Hans Jakob

2017-03-28

We present a theoretical formalism for the calculation of attosecond delays in molecular photoionization. It is shown how delays relevant to one-photon-ionization, also known as Eisenbud-Wigner-Smith delays, can be obtained from the complex dipole matrix elements provided by molecular quantum scattering theory. These results are used to derive formulae for the delays measured by two-photon attosecond interferometry based on an attosecond pulse train and a dressing femtosecond infrared pulse. These effective delays are first expressed in the molecular frame where maximal information about the molecular photoionization dynamics is available. The effects of averaging over the emission direction of the electron and the molecular orientation are introduced analytically. We illustrate this general formalism for the case of two polyatomic molecules. N 2 O serves as an example of a polar linear molecule characterized by complex photoionization dynamics resulting from the presence of molecular shape resonances. H 2 O illustrates the case of a non-linear molecule with comparably simple photoionization dynamics resulting from a flat continuum. Our theory establishes the foundation for interpreting measurements of the photoionization dynamics of all molecules by attosecond metrology.

The nucleic acid revolution continues - will forensic biology become forensic molecular biology?

PubMed

Gunn, Peter; Walsh, Simon; Roux, Claude

2014-01-01

Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to "forensic molecular biology." Aside from DNA's established role in identifying the "who" in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about "when" a crime took place and "what" took place. However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future.

Statistics Refresher for Molecular Imaging Technologists, Part 2: Accuracy of Interpretation, Significance, and Variance.

PubMed

Farrell, Mary Beth

2018-06-01

This article is the second part of a continuing education series reviewing basic statistics that nuclear medicine and molecular imaging technologists should understand. In this article, the statistics for evaluating interpretation accuracy, significance, and variance are discussed. Throughout the article, actual statistics are pulled from the published literature. We begin by explaining 2 methods for quantifying interpretive accuracy: interreader and intrareader reliability. Agreement among readers can be expressed simply as a percentage. However, the Cohen κ-statistic is a more robust measure of agreement that accounts for chance. The higher the κ-statistic is, the higher is the agreement between readers. When 3 or more readers are being compared, the Fleiss κ-statistic is used. Significance testing determines whether the difference between 2 conditions or interventions is meaningful. Statistical significance is usually expressed using a number called a probability ( P ) value. Calculation of P value is beyond the scope of this review. However, knowing how to interpret P values is important for understanding the scientific literature. Generally, a P value of less than 0.05 is considered significant and indicates that the results of the experiment are due to more than just chance. Variance, standard deviation (SD), confidence interval, and standard error (SE) explain the dispersion of data around a mean of a sample drawn from a population. SD is commonly reported in the literature. A small SD indicates that there is not much variation in the sample data. Many biologic measurements fall into what is referred to as a normal distribution taking the shape of a bell curve. In a normal distribution, 68% of the data will fall within 1 SD, 95% will fall within 2 SDs, and 99.7% will fall within 3 SDs. Confidence interval defines the range of possible values within which the population parameter is likely to lie and gives an idea of the precision of the statistic being measured. A wide confidence interval indicates that if the experiment were repeated multiple times on other samples, the measured statistic would lie within a wide range of possibilities. The confidence interval relies on the SE. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

"Mini-array" transcriptional analysis of the Listeria monocytogenes lecithinase operon as a class project: A student investigative molecular biology laboratory experience*.

PubMed

Christensen, Douglas; Jovic, Marko

2006-05-01

This report describes a molecular biotechnology-based laboratory curriculum developed to accompany an undergraduate genetics course. During the course of a semester, students researched the pathogen, developed a research question, designed experiments, and performed transcriptional analysis of a set of genes that confer virulence to the food-borne pathogen, Listeria monocytogenes. Gene fragments were amplified via PCR and utilized in "mini-arrays," a dot-blot-based format suitable for the simultaneous transcriptional analysis of multiple genes. The project provides exposure to a wide range of molecular techniques and can be easily modified for variations in class size. Data are generated at various steps of the process, allowing for student interpretation, troubleshooting, and assessment opportunities. Copyright © 2006 International Union of Biochemistry and Molecular Biology, Inc.

Molecular Phylogenetics: Concepts for a Newcomer.

PubMed

Ajawatanawong, Pravech

Molecular phylogenetics is the study of evolutionary relationships among organisms using molecular sequence data. The aim of this review is to introduce the important terminology and general concepts of tree reconstruction to biologists who lack a strong background in the field of molecular evolution. Some modern phylogenetic programs are easy to use because of their user-friendly interfaces, but understanding the phylogenetic algorithms and substitution models, which are based on advanced statistics, is still important for the analysis and interpretation without a guide. Briefly, there are five general steps in carrying out a phylogenetic analysis: (1) sequence data preparation, (2) sequence alignment, (3) choosing a phylogenetic reconstruction method, (4) identification of the best tree, and (5) evaluating the tree. Concepts in this review enable biologists to grasp the basic ideas behind phylogenetic analysis and also help provide a sound basis for discussions with expert phylogeneticists.

A method to decompose spectral changes in Synechocystis PCC 6803 during light-induced state transitions.

PubMed

Acuña, Alonso M; Kaňa, Radek; Gwizdala, Michal; Snellenburg, Joris J; van Alphen, Pascal; van Oort, Bart; Kirilovsky, Diana; van Grondelle, Rienk; van Stokkum, Ivo H M

2016-12-01

Cyanobacteria have developed responses to maintain the balance between the energy absorbed and the energy used in different pigment-protein complexes. One of the relatively rapid (a few minutes) responses is activated when the cells are exposed to high light intensities. This mechanism thermally dissipates excitation energy at the level of the phycobilisome (PB) antenna before it reaches the reaction center. When exposed to low intensities of light that modify the redox state of the plastoquinone pool, the so-called state transitions redistribute energy between photosystem I and II. Experimental techniques to investigate the underlying mechanisms of these responses, such as pulse-amplitude modulated fluorometry, are based on spectrally integrated signals. Previously, a spectrally resolved fluorometry method has been introduced to preserve spectral information. The analysis method introduced in this work allows to interpret SRF data in terms of species-associated spectra of open/closed reaction centers (RCs), (un)quenched PB and state 1 versus state 2. Thus, spectral differences in the time-dependent fluorescence signature of photosynthetic organisms under varying light conditions can be traced and assigned to functional emitting species leading to a number of interpretations of their molecular origins. In particular, we present evidence that state 1 and state 2 correspond to different states of the PB-PSII-PSI megacomplex.

CHEMKIN2. General Gas-Phase Chemical Kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rupley, F.M.

1992-01-24

CHEMKIN is a high-level tool for chemists to use to describe arbitrary gas-phase chemical reaction mechanisms and systems of governing equations. It remains, however, for the user to select and implement a solution method; this is not provided. It consists of two major components: the Interpreter and the Gas-phase Subroutine Library. The Interpreter reads a symbolic description of an arbitrary, user-specified chemical reaction mechanism. A data file is generated which forms a link to the Gas-phase Subroutine Library, a collection of about 200 modular subroutines which may be called to return thermodynamic properties, chemical production rates, derivatives of thermodynamic properties,more » derivatives of chemical production rates, or sensitivity parameters. Both single and double precision versions of CHEMKIN are included. Also provided is a set of FORTRAN subroutines for evaluating gas-phase transport properties such as thermal conductivities, viscosities, and diffusion coefficients. These properties are an important part of any computational simulation of a chemically reacting flow. The transport properties subroutines are designed to be used in conjunction with the CHEMKIN Subroutine Library. The transport properties depend on the state of the gas and on certain molecular parameters. The parameters considered are the Lennard-Jones potential well depth and collision diameter, the dipole moment, the polarizability, and the rotational relaxation collision number.« less

DNA surface hybridization regimes

PubMed Central

Gong, Ping; Levicky, Rastislav

2008-01-01

Surface hybridization reactions, in which sequence-specific recognition occurs between immobilized and solution nucleic acids, are routinely carried out to quantify and interpret genomic information. Although hybridization is fairly well understood in bulk solution, the greater complexity of an interfacial environment presents new challenges to a fundamental understanding, and hence application, of these assays. At a surface, molecular interactions are amplified by the two-dimensional nature of the immobilized layer, which focuses the nucleic acid charge and concentration to levels not encountered in solution, and which impacts the hybridization behavior in unique ways. This study finds that, at low ionic strengths, an electrostatic balance between the concentration of immobilized oligonucleotide charge and solution ionic strength governs the onset of hybridization. As ionic strength increases, the importance of electrostatics diminishes and the hybridization behavior becomes more complex. Suppression of hybridization affinity constants relative to solution values, and their weakened dependence on the concentration of DNA counterions, indicate that the immobilized strands form complexes that compete with hybridization to analyte strands. Moreover, an unusual regime is observed in which the surface coverage of immobilized oligonucleotides does not significantly influence the hybridization behavior, despite physical closeness and hence compulsory interactions between sites. These results are interpreted and summarized in a diagram of hybridization regimes that maps specific behaviors to experimental ranges of ionic strength and probe coverage. PMID:18381819

The Wacker oxidation of allyl alcohol along cyclic-intermediate routes: An ab initio molecular dynamics investigation

NASA Astrophysics Data System (ADS)

Imandi, Venkataramana; Nair, Nisanth N.

2016-09-01

The absence of isotope scrambling observed by Henry and coworkers in the Wacker oxidation of deuterated allylic alcohol was used by them as support for the inner-sphere mechanism hydroxypalladation mechanism. One of the assumptions used to interpret their experimental data was that allyl alcohol oxidation takes place through non-cyclic intermediate routes as in the case of ethene. Here we verify this assumption through ab initio metadynamics simulations of the Wacker oxidation of allyl alcohol in explicit solvent. Importance of our results in interpreting the isotope scrambling experiments is discussed.

Omics, microbial modeling, and food safety information infrastructure: a food safety perspective

USDA-ARS?s Scientific Manuscript database

Over the last three decades, advances in a variety of cutting-edge “omics” technologies, including genomics, proteomics, and metabolomics, as well as in molecular and mathematical modeling approaches have provided the ability to more easily determine and interpret the mechanisms underlying pathogene...

Chemical Principles Revisited. Proton Magnetic Resonance Spectroscopy.

ERIC Educational Resources Information Center

McQuarrie, Donald A.

1988-01-01

Discusses how to interpret nuclear magnetic resonance (NMR) spectra and how to use them to determine molecular structures. This discussion is limited to spectra that are a result of observation of only the protons in a molecule. This type is called proton magnetic resonance (PMR) spectra. (CW)

Modelling of Molecular Structures and Properties in Physical Chemistry and Biophysics, Forty-Fourth International Meeting (Modelisation des Structures et Proprietes Moleculaires en Chimie Physique et en Biophysique, Quarante- Quatrieme Reunion Internationale)

DTIC Science & Technology

1989-09-01

pyridone).Previous work on, py/ridimum, pyrazinjumn or pyrimidi im salts Koon 2 -pyrimloone and 2 - pyrimidone salts [43j have shown that some...forces. Acct . r ~[U... •K;.i. LJ , ’ 0, ’’ .t_I ..- .It . ( :.. 2 A VIBRATIONAL MOLECULAR FORCE FIELD FOR .ACROMOLECULA-R MODELLI= Gerard VERGOTENi...microscopic point of view are (1) understanding, ( 2 ) interpretation of experimental results, (3) semiquantitative estimates of experimental results and (4

An orbital localization criterion based on the theory of "fuzzy" atoms.

PubMed

Alcoba, Diego R; Lain, Luis; Torre, Alicia; Bochicchio, Roberto C

2006-04-15

This work proposes a new procedure for localizing molecular and natural orbitals. The localization criterion presented here is based on the partitioning of the overlap matrix into atomic contributions within the theory of "fuzzy" atoms. Our approach has several advantages over other schemes: it is computationally inexpensive, preserves the sigma/pi-separability in planar systems and provides a straightforward interpretation of the resulting orbitals in terms of their localization indices and atomic occupancies. The corresponding algorithm has been implemented and its efficiency tested on selected molecular systems. (c) 2006 Wiley Periodicals, Inc.

Linear indices of the "molecular pseudograph's atom adjacency matrix": definition, significance-interpretation, and application to QSAR analysis of flavone derivatives as HIV-1 integrase inhibitors.

PubMed

Marrero-Ponce, Yovani

2004-01-01

This report describes a new set of molecular descriptors of relevance to QSAR/QSPR studies and drug design, atom linear indices fk(xi). These atomic level chemical descriptors are based on the calculation of linear maps on Rn[fk(xi): Rn--> Rn] in canonical basis. In this context, the kth power of the molecular pseudograph's atom adjacency matrix [Mk(G)] denotes the matrix of fk(xi) with respect to the canonical basis. In addition, a local-fragment (atom-type) formalism was developed. The kth atom-type linear indices are calculated by summing the kth atom linear indices of all atoms of the same atom type in the molecules. Moreover, total (whole-molecule) linear indices are also proposed. This descriptor is a linear functional (linear form) on Rn. That is, the kth total linear indices is a linear map from Rn to the scalar R[ fk(x): Rn --> R]. Thus, the kth total linear indices are calculated by summing the atom linear indices of all atoms in the molecule. The features of the kth total and local linear indices are illustrated by examples of various types of molecular structures, including chain-lengthening, branching, heteroatoms-content, and multiple bonds. Additionally, the linear independence of the local linear indices to other 0D, 1D, 2D, and 3D molecular descriptors is demonstrated by using principal component analysis for 42 very heterogeneous molecules. Much redundancy and overlapping was found among total linear indices and most of the other structural indices presently in use in the QSPR/QSAR practice. On the contrary, the information carried by atom-type linear indices was strikingly different from that codified in most of the 229 0D-3D molecular descriptors used in this study. It is concluded that the local linear indices are an independent indices containing important structural information to be used in QSPR/QSAR and drug design studies. In this sense, atom, atom-type, and total linear indices were used for the prediction of pIC50 values for the cleavage process of a set of flavone derivatives inhibitors of HIV-1 integrase. Quantitative models found are significant from a statistical point of view (R of 0.965, 0.902, and 0.927, respectively) and permit a clear interpretation of the studied properties in terms of the structural features of molecules. A LOO cross-validation procedure revealed that the regression models had a fairly good predictability (q2 of 0.679, 0.543, and 0.721, respectively). The comparison with other approaches reveals good behavior of the method proposed. The approach described in this paper appears to be an excellent alternative or guides for discovery and optimization of new lead compounds.

Quantum microbiology.

PubMed

Trevors, J T; Masson, L

2011-01-01

During his famous 1943 lecture series at Trinity College Dublin, the reknown physicist Erwin Schrodinger discussed the failure and challenges of interpreting life by classical physics alone and that a new approach, rooted in Quantum principles, must be involved. Quantum events are simply a level of organization below the molecular level. This includes the atomic and subatomic makeup of matter in microbial metabolism and structures, as well as the organic, genetic information code of DNA and RNA. Quantum events at this time do not elucidate, for example, how specific genetic instructions were first encoded in an organic genetic code in microbial cells capable of growth and division, and its subsequent evolution over 3.6 to 4 billion years. However, due to recent technological advances, biologists and physicists are starting to demonstrate linkages between various quantum principles like quantum tunneling, entanglement and coherence in biological processes illustrating that nature has exerted some level quantum control to optimize various processes in living organisms. In this article we explore the role of quantum events in microbial processes and endeavor to show that after nearly 67 years, Schrödinger was prophetic and visionary in his view of quantum theory and its connection with some of the fundamental mechanisms of life.

Analysis of Students' Aptitude to Provide Meaning to Images that Represent Cellular Components at the Molecular Level

PubMed Central

Dahmani, Hassen-Reda; Schneeberger, Patricia

2009-01-01

The number of experimentally derived structures of cellular components is rapidly expanding, and this phenomenon is accompanied by the development of a new semiotic system for teaching. The infographic approach is shifting from a schematic toward a more realistic representation of cellular components. By realistic we mean artist-prepared or computer graphic images that closely resemble experimentally derived structures and are characterized by a low level of styling and simplification. This change brings about a new challenge for teachers: designing course instructions that allow students to interpret these images in a meaningful way. To determine how students deal with this change, we designed several image-based, in-course assessments. The images were highly relevant for the cell biology course but did not resemble any of the images in the teaching documents. We asked students to label the cellular components, describe their function, or both. What we learned from these tests is that realistic images, with a higher apparent level of complexity, do not deter students from investigating their meaning. When given a choice, the students do not necessarily choose the most simplified representation, and they were sensitive to functional indications embedded in realistic images. PMID:19723817

5-Lipoxygenase as an endogenous modulator of amyloid beta formation in vivo

PubMed Central

Chu, Jin; Praticò, Domenico

2010-01-01

Objective The 5-lipoxygenase (5-LO) enzymatic pathway is widely distributed within the central nervous system, and is up-regulated in Alzheimer's disease. However, the mechanism whereby it may influence the disease pathogenesis remains elusive. Methods We evaluated the molecular mechanism by which 5-LO regulates Amyloid β (Aβ) formation in vitro and in vivo by pharmacological and genetic approaches. Results Here we show that 5-LO regulates the formation of Aβ by activating the cAMP-response element binding protein (CREB), which in turn increases transcription of the γ-secretase complex. Preventing CREB activation by pharmacologic inhibition or dominant negative mutants blocks the 5-LO-dependent elevation of Aβ formation and the increase of γ-secretase mRNA and protein levels. Moreover, 5-LO targeted gene disruption or its in vivo selective pharmacological inhibition results in a significant reduction of Aβ, CREB and γ-secretase levels. Interpretation These data establish a novel functional role for 5-LO in regulating endogenous formation of Aβ levels in the central nervous system. Thus, 5-LO pharmacological inhibition may be beneficial in the treatment and prevention of Alzheimer's disease. PMID:21280074

La interpretacion consecutiva: metodologia y tecnicas (Consecutive Interpretation: Methodology and Techniques).

ERIC Educational Resources Information Center

Drallny, Ines

1987-01-01

Describes the purpose and appropriate methodology for various levels of interpreter training, for both consecutive and simultaneous interpretation. The importance of relating the intent of the text to the explicit language forms through which that intent is realized is discussed, and appropriate criteria for evaluation of student interpreters are…

The importance of being apt: metaphor comprehension in Alzheimer's disease

PubMed Central

Roncero, Carlos; de Almeida, Roberto G.

2014-01-01

We investigated the effect of aptness in the comprehension of copular metaphors (e.g., Lawyers are sharks) by Alzheimer's Disease (AD) patients. Aptness is the extent to which the vehicle (e.g., shark) captures salient properties of the topic (e.g., lawyers). A group of AD patients provided interpretations for metaphors that varied both in aptness and familiarity. Compared to healthy controls, AD patients produced worse interpretations, but interpretation ability was related to a metaphor's aptness rather than to its familiarity level, and patients with superior abstraction ability produced better interpretations. Therefore, the ability to construct figurative interpretations for metaphors is not always diminished in AD patients nor is it dependent only on the novelty level of the expression. We show that Alzheimer's patients' capacity to build figurative interpretations for metaphors is related to both item variables, such as aptness, and participant variables, such as abstraction ability. PMID:25520642

Phoenix 100 versus Vitek 2 in the Identification of Gram-Positive and Gram-Negative Bacteria: a Comprehensive Meta-Analysis▿†

PubMed Central

Chatzigeorgiou, Kalliopi-Stavroula; Sergentanis, Theodoros N.; Tsiodras, Sotirios; Hamodrakas, Stavros J.; Bagos, Pantelis G.

2011-01-01

Phoenix 100 and Vitek 2 (operating with the current colorimetric cards) are commonly used in hospital laboratories for rapid identification of microorganisms. The present meta-analysis aims to evaluate and compare their performance on Gram-positive and Gram-negative bacteria. The MEDLINE database was searched up to October 2010 for the retrieval of relevant articles. Pooled correct identification rates were derived from random-effects models, using the arcsine transformation. Separate analyses were conducted at the genus and species levels; subanalyses and meta-regression were undertaken to reveal meaningful system- and study-related modifiers. A total of 29 (6,635 isolates) and 19 (4,363 isolates) articles were eligible for Phoenix and colorimetric Vitek 2, respectively. No significant differences were observed between Phoenix and Vitek 2 either at the genus (97.70% versus 97.59%, P = 0.919) or the species (92.51% versus 88.77%, P = 0.149) level. Studies conducted with conventional comparator methods tended to report significantly better results compared to those using molecular reference techniques. Speciation of Staphylococcus aureus was significantly more accurate in comparison to coagulase-negative staphylococci by both Phoenix (99.78% versus 88.42%, P < 0.00001) and Vitek 2 (98.22% versus 91.89%, P = 0.043). Vitek 2 also reached higher correct identification rates for Gram-negative fermenters versus nonfermenters at the genus (99.60% versus 95.90%, P = 0.004) and the species (97.42% versus 84.85%, P = 0.003) level. In conclusion, the accuracy of both systems seems modified by underlying sample- and comparator method-related parameters. Future simultaneous assessment of the instruments against molecular comparator procedures may facilitate interpretation of the current observations. PMID:21752980

Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing

PubMed Central

Chan, Rebecca W. Y.; Jiang, Peiyong; Peng, Xianlu; Tam, Lai-Shan; Liao, Gary J. W.; Li, Edmund K. M.; Wong, Priscilla C. H.; Sun, Hao; Chan, K. C. Allen; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2014-01-01

We performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double–stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments. The extent of plasma DNA shortening in SLE patients correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA antibody level. Third, the plasma DNA of active SLE patients showed decreased methylation densities. The extent of hypomethylation correlated with SLEDAI and anti-dsDNA antibody level. To explore the impact of anti-dsDNA antibody on plasma DNA in SLE, a column-based protein G capture approach was used to fractionate the IgG-bound and non–IgG-bound DNA in plasma. Compared with healthy individuals, SLE patients had higher concentrations of IgG-bound DNA in plasma. More IgG binding occurs at genomic locations showing increased MGRs. Furthermore, the IgG-bound plasma DNA was shorter in size and more hypomethylated than the non–IgG-bound plasma DNA. These observations have enhanced our understanding of the spectrum of plasma DNA aberrations in SLE and may provide new molecular markers for SLE. Our results also suggest that caution should be exercised when interpreting plasma DNA-based noninvasive prenatal testing and cancer testing conducted for SLE patients. PMID:25427797

A receptor-based model for dopamine-induced fMRI signal

PubMed Central

Mandeville, Joseph. B.; Sander, Christin Y. M.; Jenkins, Bruce G.; Hooker, Jacob M.; Catana, Ciprian; Vanduffel, Wim; Alpert, Nathaniel M.; Rosen, Bruce R.; Normandin, Marc D.

2013-01-01

This report describes a multi-receptor physiological model of the fMRI temporal response and signal magnitude evoked by drugs that elevate synaptic dopamine in basal ganglia. The model is formulated as a summation of dopamine’s effects at D1-like and D2-like receptor families, which produce functional excitation and inhibition, respectively, as measured by molecular indicators like adenylate cyclase or neuroimaging techniques like fMRI. Functional effects within the model are described in terms of relative changes in receptor occupancies scaled by receptor densities and neuro-vascular coupling constants. Using literature parameters, the model reconciles many discrepant observations and interpretations of pre-clinical data. Additionally, we present data showing that amphetamine stimulation produces fMRI inhibition at low doses and a biphasic response at higher doses in the basal ganglia of non-human primates (NHP), in agreement with model predictions based upon the respective levels of evoked dopamine. Because information about dopamine release is required to inform the fMRI model, we simultaneously acquired PET 11C-raclopride data in several studies to evaluate the relationship between raclopride displacement and assumptions about dopamine release. At high levels of dopamine release, results suggest that refinements of the model will be required to consistently describe the PET and fMRI data. Overall, the remarkable success of the model in describing a wide range of preclinical fMRI data indicate that this approach will be useful for guiding the design and analysis of basic science and clinical investigations and for interpreting the functional consequences of dopaminergic stimulation in normal subjects and in populations with dopaminergic neuroadaptations. PMID:23466936

Toward extending the educational interpreter performance assessment to cued speech.

PubMed

Krause, Jean C; Kegl, Judy A; Schick, Brenda

2008-01-01

The Educational Interpreter Performance Assessment (EIPA) is as an important research tool for examining the quality of interpreters who use American Sign Language or a sign system in classroom settings, but it is not currently applicable to educational interpreters who use Cued Speech (CS). In order to determine the feasibility of extending the EIPA to include CS, a pilot EIPA test was developed and administered to 24 educational CS interpreters. Fifteen of the interpreters' performances were evaluated two to three times in order to assess reliability. Results show that the instrument has good construct validity and test-retest reliability. Although more interrater reliability data are needed, intrarater reliability was quite high (0.9), suggesting that the pilot test can be rated as reliably as signing versions of the EIPA. Notably, only 48% of interpreters who formally participated in pilot testing performed at a level that could be considered minimally acceptable. In light of similar performance levels previously reported for interpreters who sign (e.g., Schick, Williams, & Kupermintz, 2006), these results suggest that interpreting services for deaf and hard-of hearing students, regardless of the communication option used, are often inadequate and could seriously hinder access to the classroom environment.

A Decision Support Framework for Genomically Informed Investigational Cancer Therapy

PubMed Central

Johnson, Amber; Holla, Vijaykumar; Bailey, Ann Marie; Brusco, Lauren; Chen, Ken; Routbort, Mark; Patel, Keyur P.; Zeng, Jia; Kopetz, Scott; Davies, Michael A.; Piha-Paul, Sarina A.; Hong, David S.; Eterovic, Agda Karina; Tsimberidou, Apostolia M.; Broaddus, Russell; Bernstam, Elmer V.; Shaw, Kenna R.; Mendelsohn, John; Mills, Gordon B.

2015-01-01

Rapidly improving understanding of molecular oncology, emerging novel therapeutics, and increasingly available and affordable next-generation sequencing have created an opportunity for delivering genomically informed personalized cancer therapy. However, to implement genomically informed therapy requires that a clinician interpret the patient’s molecular profile, including molecular characterization of the tumor and the patient’s germline DNA. In this Commentary, we review existing data and tools for precision oncology and present a framework for reviewing the available biomedical literature on therapeutic implications of genomic alterations. Genomic alterations, including mutations, insertions/deletions, fusions, and copy number changes, need to be curated in terms of the likelihood that they alter the function of a “cancer gene” at the level of a specific variant in order to discriminate so-called “drivers” from “passengers.” Alterations that are targetable either directly or indirectly with approved or investigational therapies are potentially “actionable.” At this time, evidence linking predictive biomarkers to therapies is strong for only a few genomic markers in the context of specific cancer types. For these genomic alterations in other diseases and for other genomic alterations, the clinical data are either absent or insufficient to support routine clinical implementation of biomarker-based therapy. However, there is great interest in optimally matching patients to early-phase clinical trials. Thus, we need accessible, comprehensive, and frequently updated knowledge bases that describe genomic changes and their clinical implications, as well as continued education of clinicians and patients. PMID:25863335

From Peptides to Proteins: Systematic Control of Net Molecular Charge and Hydrophilicity on the Kinetics of Calcite Growth

NASA Astrophysics Data System (ADS)

Elhadj, S.; de Yoreo, J. J.; Hoyer, J. J.; Dove, P. M.

2006-12-01

The compartment-specific compositions of biologic molecules isolated from biominerals suggest that control of mineral growth may be linked to biochemical features. Here we define a systematic relationship between the ability of biomolecules in solution to promote the growth of calcite (CaCO3) and their net negative molecular charge and hydrophilicity. The degree of enhancement is dependent on peptide composition, but not on peptide sequence. Data analysis shows that this rate enhancement arises from an increase in the kinetic coefficient. We interpret the mechanism of growth enhancement to be a catalytic process whereby biomolecules reduce the magnitude of the diffusive barrier, Ek, by perturbations that displace water molecules- a water shell destruction mechanism. The result is a decrease in the repulsive barrier for attachment of solutes to the solid phase. This previously unrecognized relationship also rationalizes recently reported data showing acceleration of calcite growth rates over rates measured in the pure system by nanomolar levels of abalone nacre proteins. These findings show that the growth-modifying properties of small model peptides may be scaled up to analyze mineralization processes that are mediated by more complex proteins. We suggest that enhancement of calcite growth may now be estimated a priori from the composition of peptide sequences and the calculated values of hydrophilicity and net molecular charge without need for detailed tests for each biomolecule. This insight may contribute to an improved understanding of mineralization in diverse systems of biomineralization.

The spontaneous synchronized dance of pairs of water molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roncaratti, Luiz F.; Instituto de Física, Universidade de Brasília, 70910-900 Brasília; Cappelletti, David, E-mail: david.cappelletti@unipg.it

2014-03-28

Molecular beam scattering experiments have been performed to study the effect of long-range anisotropic forces on the collision dynamics of two small polar molecules. The main focus of this paper is on water, but also ammonia and hydrogen sulphide molecules have been investigated, and some results will be anticipated. The intermolecular distances mainly probed are of the order of 1 nm and therefore much larger than the molecular dimensions. In particular, we have found that the natural electric field gradient, generated by different spatial orientations of the permanent electric dipoles, is able to promote the transformation of free rotations into coupledmore » pendular states, letting the molecular partners involved in the collision complex swinging to and fro around the field direction. This long-ranged concerted motion manifested itself as large increases of the magnitude of the total integral cross section. The experimental findings and the theoretical treatment developed to shed light on the details of the process suggest that the transformation from free rotations to pendular states depends on the rotational level of both molecules, on the impact parameter, on the relative collision velocity, on the dipole moment product and occurs in the time scale of picoseconds. The consequences of this intriguing phenomenon may be important for the interpretation and, in perspective, for the control of elementary chemical and biological processes, given by polar molecules, ions, and free radicals, occurring in several environments under various conditions.« less

Deciphering associations between dissolved organic molecules and bacterial communities in a pelagic marine system

PubMed Central

Osterholz, Helena; Singer, Gabriel; Wemheuer, Bernd; Daniel, Rolf; Simon, Meinhard; Niggemann, Jutta; Dittmar, Thorsten

2016-01-01

Dissolved organic matter (DOM) is the main substrate and energy source for heterotrophic bacterioplankton. To understand the interactions between DOM and the bacterial community (BC), it is important to identify the key factors on both sides in detail, chemically distinct moieties in DOM and the various bacterial taxa. Next-generation sequencing facilitates the classification of millions of reads of environmental DNA and RNA amplicons and ultrahigh-resolution mass spectrometry yields up to 10 000 DOM molecular formulae in a marine water sample. Linking this detailed biological and chemical information is a crucial first step toward a mechanistic understanding of the role of microorganisms in the marine carbon cycle. In this study, we interpreted the complex microbiological and molecular information via a novel combination of multivariate statistics. We were able to reveal distinct relationships between the key factors of organic matter cycling along a latitudinal transect across the North Sea. Total BC and DOM composition were mainly driven by mixing of distinct water masses and presumably retain their respective terrigenous imprint on similar timescales on their way through the North Sea. The active microbial community, however, was rather influenced by local events and correlated with specific DOM molecular formulae indicative of compounds that are easily degradable. These trends were most pronounced on the highest resolved level, that is, operationally defined ‘species', reflecting the functional diversity of microorganisms at high taxonomic resolution. PMID:26800236

Molecular dynamics simulation of bovine pancreatic ribonuclease A-CpA and transition state-like complexes.

PubMed

Formoso, Elena; Matxain, Jon M; Lopez, Xabier; York, Darrin M

2010-06-03

The mechanisms of enzymes are intimately connected with their overall structure and dynamics in solution. Experimentally, it is considerably challenging to provide detailed atomic level information about the conformational events that occur at different stages along the chemical reaction path. Here, theoretical tools may offer new potential insights that complement those obtained from experiments that may not yield an unambiguous mechanistic interpretation. In this study, we apply molecular dynamics simulations of bovine pancreatic ribonuclease A, an archetype ribonuclease, to study the conformational dynamics, structural relaxation, and differential solvation that occur at discrete stages of the transesterification and cleavage reaction. Simulations were performed with explicit solvation with rigorous electrostatics and utilize recently developed molecular mechanical force field parameters for transphosphorylation and hydrolysis transition state analogues. Herein, we present results for the enzyme complexed with the dinucleotide substrate cytidilyl-3',5'-adenosine (CpA) in the reactant, and transphosphorylation and hydrolysis transition states. A detailed analysis of active site structures and hydrogen-bond patterns is presented and compared. The integrity of the overall backbone structure is preserved in the simulations and supports a mechanism whereby His12 stabilizes accumulating negative charge at the transition states through hydrogen-bond donation to the nonbridge oxygens. Lys41 is shown to be highly versatile along the reaction coordinate and can aid in the stabilization of the dianionic transition state, while being poised to act as a general acid catalyst in the hydrolysis step.

Molecular Dynamics Simulation of Bovine Pancreatic Ribonuclease A - CpA and Transition State-like Complexes

PubMed Central

Formoso, Elena; Matxain, Jon M.; Lopez, Xabier; York, Darrin M.

2010-01-01

The mechanisms of enzymes are intimately connected with their overall structure and dynamics in solution. Experimentally it is considerably challenging to provide detailed atomic level information about the conformational events that occur at different stages along the chemical reaction path. Here, theoretical tools may offer new potential insights that complement those obtained from experiments that may not yield an unambiguous mechanistic interpretation. In this study we apply molecular dynamics simulations of bovine pancreatic ribonuclease A, an archetype ribonuclease, in order to study the conformational dynamics, structural relaxation, and differential solvation that occurs at discreet stages of the transesterification and cleavage reaction. Simulations were performed with explicit solvation with rigorous electrostatics, and utilize recently developed molecular mechanical force field parameters for transphosphorylation and hydrolysis transition state analogs. Herein, we present results for the enzyme complexed with the dinucleotide substrate cytidilyl-3′,5′-adenosine (CpA) in the reactant, and transphosphorylation and hydrolysis transition states. A detailed analysis of active site structures and hydrogen bond patterns are presented and compared. The integrity of the overall backbone structure is preserved in the simulations, and support a mechanism whereby His12 stabilizes accumulating negative charge at the transition states through hydrogen bond donation to the non-bridge oxygens. Lys41 is shown to be highly versatile along the reaction coordinate, and can aid in the stabilization of the dianionic transition state, while being poised to act as a general acid catalyst in the hydrolysis step. PMID:20455590

Biophysical characteristics of proteins and living cells exposed to the green tea polyphenol epigallocatechin-3-gallate (EGCg): review of recent advances from molecular mechanisms to nanomedicine and clinical trials.

PubMed

Peter, Beatrix; Bosze, Szilvia; Horvath, Robert

2017-01-01

Herbs and traditional medicines have been applied for thousands of years, but researchers started to study their mode of action at the molecular, cellular and tissue levels only recently. Nowadays, just like in ancient times, natural compounds are still determining factors in remedies. To support this statement, the recently won Nobel Prize for an anti-malaria agent from the plant sweet wormwood, which had been used to effectively treat the disease, could be mentioned. Among natural compounds and traditional Chinese medicines, the green tea polyphenol epigallocatechin gallate (EGCg) is one of the most studied active substances. In the present review, we summarize the molecular scale interactions of proteins and EGCg with special focus on its limited stability and antioxidant properties. We outline the observed biophysical effects of EGCg on various cell lines and cultures. The alteration of cell adhesion, motility, migration, stiffness, apoptosis, proliferation as well as the different impacts on normal and cancer cells are all reviewed. We also handle the works performed using animal models, microbes and clinical trials. Novel ways to develop its utilization for therapeutic purposes in the future are discussed too, for instance, using nanoparticles and green tea polyphenols together to cure illnesses and the combination of EGCg and anticancer compounds to intensify their effects. The limitations of the employed experimental models and criticisms of the interpretation of the obtained experimental data are summarized as well.

Molecular structure, vibrational spectra and DFT computational studies of melaminium N-acetylglycinate dihydrate

NASA Astrophysics Data System (ADS)

Tanak, H.; Pawlus, K.; Marchewka, M. K.

2016-10-01

Melaminium N-acetylglycinate dihydrate, an organic material has been synthesized and characterized by X-ray diffraction, FT-IR, and FT-Raman spectroscopies for the protiated and deuteriated crystals. The title complex crystallizes in the triclinic system, and the space group is P-1 with a = 5.642(1) Å, b = 7.773(2) Å, c = 15.775(3) Å, α = 77.28(1)°, β = 84.00(1)°, γ = 73.43(1)° and Z = 2. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on density functional method (B3LYP) with the 6-311++G(d,p) basis set. The obtained vibrational wavenumbers and optimized geometric parameters were seen to be in good agreement with the experimental data. The intermolecular hydrogen bonding interactions of the title compound have been investigated using the natural bonding orbital analysis. It reveals that the O-H···O, N-H···N and N-H···O intermolecular interactions significantly influence crystal packing of this molecule. The non-linear optical properties are also addressed theoretically. The predicted NLO properties of the title compound are much greater than ones of urea. In addition, DFT calculations of the title compound, molecular electrostatic potential, thermodynamic properties, frontier orbitals and chemical reactivity descriptors were also performed at 6-311++G(d,p) level of theory.

Isolation & characterization of Brucella melitensis isolated from patients suspected for human brucellosis in India

PubMed Central

Barua, Anita; Kumar, Ashu; Thavaselvam, Duraipandian; Mangalgi, Smita; Prakash, Archana; Tiwari, Sapana; Arora, Sonia; Sathyaseelan, Kannusamy

2016-01-01

Background & objectives: Brucellosis is endemic in the southern part of India. A combination of biochemical, serological and molecular methods is required for identification and biotyping of Brucella. The present study describes the isolation and biochemical, molecular characterization of Brucella melitensis from patients suspected for human brucellosis. Methods: The blood samples were collected from febrile patients suspected to have brucellosis. A total of 18 isolates were obtained from 102 blood samples subjected to culture. The characterization of these 18 isolates was done by growth on Brucella specific medium, biochemical reactions, CO2 requirement, H2S production, agglutination with A and M mono-specific antiserum, dye sensitivity to basic fuchsin and thionin. Further, molecular characterization of the isolates was done by amplification of B. melitensis species specific IS711 repetitive DNA fragment and 16S (rRNA) sequence analysis. PCR-restriction fragment length polymorphism (RFLP) analysis of omp2 locus and IS711 gene was also done for molecular characterization. Results: All 102 suspected samples were subjected to bacteria isolation and of these, 18 isolates could be recovered on blood culture. The biochemical, PCR and PCR-RFLP and 16s rRNA sequencing revealed that all isolates were of B. melitensis and matched exactly with reference strain B. melitensis 16M. Interpretation & conclusions: The present study showed an overall isolation rate of 17.64 per cent for B. melitensis. There is a need to establish facilities for isolation and characterization of Brucella species for effective clinical management of the disease among patients as well as surveillance and control of infection in domestic animals. Further studies are needed from different geographical areas of the country with different level of endemicity to plan and execute control strategies against human brucellosis. PMID:27488010

Development and in silico evaluation of large-scale metabolite identification methods using functional group detection for metabolomics

PubMed Central

Mitchell, Joshua M.; Fan, Teresa W.-M.; Lane, Andrew N.; Moseley, Hunter N. B.

2014-01-01

Large-scale identification of metabolites is key to elucidating and modeling metabolism at the systems level. Advances in metabolomics technologies, particularly ultra-high resolution mass spectrometry (MS) enable comprehensive and rapid analysis of metabolites. However, a significant barrier to meaningful data interpretation is the identification of a wide range of metabolites including unknowns and the determination of their role(s) in various metabolic networks. Chemoselective (CS) probes to tag metabolite functional groups combined with high mass accuracy provide additional structural constraints for metabolite identification and quantification. We have developed a novel algorithm, Chemically Aware Substructure Search (CASS) that efficiently detects functional groups within existing metabolite databases, allowing for combined molecular formula and functional group (from CS tagging) queries to aid in metabolite identification without a priori knowledge. Analysis of the isomeric compounds in both Human Metabolome Database (HMDB) and KEGG Ligand demonstrated a high percentage of isomeric molecular formulae (43 and 28%, respectively), indicating the necessity for techniques such as CS-tagging. Furthermore, these two databases have only moderate overlap in molecular formulae. Thus, it is prudent to use multiple databases in metabolite assignment, since each major metabolite database represents different portions of metabolism within the biosphere. In silico analysis of various CS-tagging strategies under different conditions for adduct formation demonstrate that combined FT-MS derived molecular formulae and CS-tagging can uniquely identify up to 71% of KEGG and 37% of the combined KEGG/HMDB database vs. 41 and 17%, respectively without adduct formation. This difference between database isomer disambiguation highlights the strength of CS-tagging for non-lipid metabolite identification. However, unique identification of complex lipids still needs additional information. PMID:25120557

Gamma-ray observations of the Orion Molecular Clouds with the Fermi Large Area Telescope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackermann, M.; Ajello, M.; Allafort, A.

We report on the gamma-ray observations of giant molecular clouds Orion A and B with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. The gamma-ray emission in the energy band between ~100 MeV and ~100 GeV is predicted to trace the gas mass distribution in the clouds through nuclear interactions between the Galactic cosmic rays (CRs) and interstellar gas. The gamma-ray production cross-section for the nuclear interaction is known to ~10% precision which makes the LAT a powerful tool to measure the gas mass column density distribution of molecular clouds for a known CR intensity. Wemore » present here such distributions for Orion A and B, and correlate them with those of the velocity-integrated CO intensity (W CO) at a 1° × 1° pixel level. The correlation is found to be linear over a W CO range of ~10-fold when divided in three regions, suggesting penetration of nuclear CRs to most of the cloud volumes. The W CO-to-mass conversion factor, X CO, is found to be ~2.3 × 10 20 cm -2(K km s –1) –1 for the high-longitude part of Orion A (l > 212°), ~1.7 times higher than ~1.3 × 10 20 found for the rest of Orion A and B. We interpret the apparent high X CO in the high-longitude region of Orion A in the light of recent works proposing a nonlinear relation between H2 and CO densities in the diffuse molecular gas. W CO decreases faster than the H 2 column density in the region making the gas "darker" to W CO.« less

Gamma-Ray Observations of the Orion Molecular Clouds with the Fermi Large Area Telescope

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Allafort, A.; Antolini, E.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.;

Cued Speech Transliteration: Effects of Speaking Rate and Lag Time on Production Accuracy

PubMed Central

Tessler, Morgan P.

2016-01-01

Many deaf and hard-of-hearing children rely on interpreters to access classroom communication. Although the exact level of access provided by interpreters in these settings is unknown, it is likely to depend heavily on interpreter accuracy (portion of message correctly produced by the interpreter) and the factors that govern interpreter accuracy. In this study, the accuracy of 12 Cued Speech (CS) transliterators with varying degrees of experience was examined at three different speaking rates (slow, normal, fast). Accuracy was measured with a high-resolution, objective metric in order to facilitate quantitative analyses of the effect of each factor on accuracy. Results showed that speaking rate had a large negative effect on accuracy, caused primarily by an increase in omitted cues, whereas the effect of lag time on accuracy, also negative, was quite small and explained just 3% of the variance. Increased experience level was generally associated with increased accuracy; however, high levels of experience did not guarantee high levels of accuracy. Finally, the overall accuracy of the 12 transliterators, 54% on average across all three factors, was low enough to raise serious concerns about the quality of CS transliteration services that (at least some) children receive in educational settings. PMID:27221370

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics.

PubMed

Paschke, Ralf; Cantara, Silvia; Crescenzi, Anna; Jarzab, Barbara; Musholt, Thomas J; Sobrinho Simoes, Manuel

2017-07-01

Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF , NRAS , HRAS , KRAS , PAX8/PPARG , RET/PTC ) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

PubMed Central

Paschke, Ralf; Cantara, Silvia; Crescenzi, Anna; Jarzab, Barbara; Musholt, Thomas J.; Sobrinho Simoes, Manuel

2017-01-01

Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation. PMID:28785538

A Comparison of Molecular Vibrational Theory to Huckel Molecular Orbital Theory.

ERIC Educational Resources Information Center

Keeports, David

1986-01-01

Compares the similar mathematical problems of molecular vibrational calculations (at any intermediate level of sophistication) and molecular orbital calculations (at the Huckel level). Discusses how the generalizations of Huckel treatment of molecular orbitals apply to vibrational theory. (TW)

Methodological challenges in qualitative content analysis: A discussion paper.

PubMed

Graneheim, Ulla H; Lindgren, Britt-Marie; Lundman, Berit

2017-09-01

This discussion paper is aimed to map content analysis in the qualitative paradigm and explore common methodological challenges. We discuss phenomenological descriptions of manifest content and hermeneutical interpretations of latent content. We demonstrate inductive, deductive, and abductive approaches to qualitative content analysis, and elaborate on the level of abstraction and degree of interpretation used in constructing categories, descriptive themes, and themes of meaning. With increased abstraction and interpretation comes an increased challenge to demonstrate the credibility and authenticity of the analysis. A key issue is to show the logic in how categories and themes are abstracted, interpreted, and connected to the aim and to each other. Qualitative content analysis is an autonomous method and can be used at varying levels of abstraction and interpretation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biological event composition

PubMed Central

2012-01-01

Background In recent years, biological event extraction has emerged as a key natural language processing task, aiming to address the information overload problem in accessing the molecular biology literature. The BioNLP shared task competitions have contributed to this recent interest considerably. The first competition (BioNLP'09) focused on extracting biological events from Medline abstracts from a narrow domain, while the theme of the latest competition (BioNLP-ST'11) was generalization and a wider range of text types, event types, and subject domains were considered. We view event extraction as a building block in larger discourse interpretation and propose a two-phase, linguistically-grounded, rule-based methodology. In the first phase, a general, underspecified semantic interpretation is composed from syntactic dependency relations in a bottom-up manner. The notion of embedding underpins this phase and it is informed by a trigger dictionary and argument identification rules. Coreference resolution is also performed at this step, allowing extraction of inter-sentential relations. The second phase is concerned with constraining the resulting semantic interpretation by shared task specifications. We evaluated our general methodology on core biological event extraction and speculation/negation tasks in three main tracks of BioNLP-ST'11 (GENIA, EPI, and ID). Results We achieved competitive results in GENIA and ID tracks, while our results in the EPI track leave room for improvement. One notable feature of our system is that its performance across abstracts and articles bodies is stable. Coreference resolution results in minor improvement in system performance. Due to our interest in discourse-level elements, such as speculation/negation and coreference, we provide a more detailed analysis of our system performance in these subtasks. Conclusions The results demonstrate the viability of a robust, linguistically-oriented methodology, which clearly distinguishes general semantic interpretation from shared task specific aspects, for biological event extraction. Our error analysis pinpoints some shortcomings, which we plan to address in future work within our incremental system development methodology. PMID:22759461

Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis.

PubMed

Martínez, Leandro

2015-01-01

The analysis of structural mobility in molecular dynamics plays a key role in data interpretation, particularly in the simulation of biomolecules. The most common mobility measures computed from simulations are the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuations (RMSF) of the structures. These are computed after the alignment of atomic coordinates in each trajectory step to a reference structure. This rigid-body alignment is not robust, in the sense that if a small portion of the structure is highly mobile, the RMSD and RMSF increase for all atoms, resulting possibly in poor quantification of the structural fluctuations and, often, to overlooking important fluctuations associated to biological function. The motivation of this work is to provide a robust measure of structural mobility that is practical, and easy to interpret. We propose a Low-Order-Value-Optimization (LOVO) strategy for the robust alignment of the least mobile substructures in a simulation. These substructures are automatically identified by the method. The algorithm consists of the iterative superposition of the fraction of structure displaying the smallest displacements. Therefore, the least mobile substructures are identified, providing a clearer picture of the overall structural fluctuations. Examples are given to illustrate the interpretative advantages of this strategy. The software for performing the alignments was named MDLovoFit and it is available as free-software at: http://leandro.iqm.unicamp.br/mdlovofit.

Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management.

PubMed

Chandler, Natalie; Best, Sunayna; Hayward, Jane; Faravelli, Francesca; Mansour, Sahar; Kivuva, Emma; Tapon, Dagmar; Male, Alison; DeVile, Catherine; Chitty, Lyn S

2018-03-29

PurposeUnexpected fetal abnormalities occur in 2-5% of pregnancies. While traditional cytogenetic and microarray approaches achieve diagnosis in around 40% of cases, lack of diagnosis in others impedes parental counseling, informed decision making, and pregnancy management. Postnatally exome sequencing yields high diagnostic rates, but relies on careful phenotyping to interpret genotype results. Here we used a multidisciplinary approach to explore the utility of rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as an exemplar.MethodsParents in pregnancies undergoing invasive testing because of sonographic fetal abnormalities, where multidisciplinary review considered skeletal dysplasia a likely etiology, were consented for exome trio sequencing (both parents and fetus). Variant interpretation focused on a virtual panel of 240 genes known to cause skeletal dysplasias.ResultsDefinitive molecular diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings alone were of sufficient severity for parents to opt for termination. In others, molecular diagnosis informed accurate prediction of outcome, improved parental counseling, and enabled parents to terminate or continue the pregnancy with certainty.ConclusionTrio sequencing with expert multidisciplinary review for case selection and data interpretation yields timely, high diagnostic rates in fetuses presenting with unexpected skeletal abnormalities. This improves parental counseling and pregnancy management.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.30.

Automatic Identification of Mobile and Rigid Substructures in Molecular Dynamics Simulations and Fractional Structural Fluctuation Analysis

PubMed Central

Martínez, Leandro

2015-01-01

The analysis of structural mobility in molecular dynamics plays a key role in data interpretation, particularly in the simulation of biomolecules. The most common mobility measures computed from simulations are the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuations (RMSF) of the structures. These are computed after the alignment of atomic coordinates in each trajectory step to a reference structure. This rigid-body alignment is not robust, in the sense that if a small portion of the structure is highly mobile, the RMSD and RMSF increase for all atoms, resulting possibly in poor quantification of the structural fluctuations and, often, to overlooking important fluctuations associated to biological function. The motivation of this work is to provide a robust measure of structural mobility that is practical, and easy to interpret. We propose a Low-Order-Value-Optimization (LOVO) strategy for the robust alignment of the least mobile substructures in a simulation. These substructures are automatically identified by the method. The algorithm consists of the iterative superposition of the fraction of structure displaying the smallest displacements. Therefore, the least mobile substructures are identified, providing a clearer picture of the overall structural fluctuations. Examples are given to illustrate the interpretative advantages of this strategy. The software for performing the alignments was named MDLovoFit and it is available as free-software at: http://leandro.iqm.unicamp.br/mdlovofit PMID:25816325

Update on the Culicoides sonorensis transcriptome project: a peek into the molecular biology of the midge

USDA-ARS?s Scientific Manuscript database

Next Generation Sequencing is transforming the way scientists collect and measure an organism’s genetic background and gene dynamics, while bioinformatics and super-computing are merging to facilitate parallel sample computation and interpretation at unprecedented speeds. Analyzing the complete gene...

Students' Visual Learning Disabilities and Under-Achievement in Selected Science Subjects.

ERIC Educational Resources Information Center

Rochford, Kevin

Two experiments were conducted to assess the performance of freshmen chemistry students with poor spatial visualization skills. In the first experiment, 31 chemistry students with academically deficient backgrounds completed a diagnostic test of their ability to visualize and interpret pictorial representations of simple molecular structures. At…

ITRAQ MASS SPECTROMETRIC PROTEOMIC APPLICATIONS FOR IN VIVO TOXICOLOGY STUDIES OF AMPHIBIAN SPECIES: DATA HANDLING AND INTERPRETATION USING PEPTIDE-TAGGING SOFTWARE

EPA Science Inventory

This addresses the USEPA's need for a cost effective, non-mammalian screening assay for thyroid axis disrupting chemicals; a multi-endpoint strategy combining molecular and in vivo protocols in an amphibian model is being applied at MED Duluth.

Frameworks for organizing exposure and toxicity data - the Aggregate Exposure Pathway (AEP) and the Adverse Outcome Pathway (AOP)

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework organizes existing knowledge regarding a series of biological events, starting with a molecular initiating event (MIE) and ending at an adverse outcome. The AOP framework provides a biological context to interpret in vitro toxicity dat...

The Band Structure of Polymers: Its Calculation and Interpretation. Part 2. Calculation.

ERIC Educational Resources Information Center

Duke, B. J.; O'Leary, Brian

1988-01-01

Details ab initio crystal orbital calculations using all-trans-polyethylene as a model. Describes calculations based on various forms of translational symmetry. Compares these calculations with ab initio molecular orbital calculations discussed in a preceding article. Discusses three major approximations made in the crystal case. (CW)

Learning Molecular Genetics in Teacher-Led Outreach Laboratories

ERIC Educational Resources Information Center

Ben-Nun, Michal Stolarsky; Yarden, Anat

2009-01-01

Learning modern genetics is challenging and students have difficulty acquiring a coherent cognitive mental model of abstract concepts such as DNA, bacteria and enzymes. Here we investigated students' mental models of genetics through analysis and interpretation of the discourse that took place while high-school students practised hands-on…