Sample records for molecular aspects integrative

  1. Molecular aspects of defence priming.

    PubMed

    Conrath, Uwe

    2011-10-01

    Plants can be primed for more rapid and robust activation of defence to biotic or abiotic stress. Priming follows perception of molecular patterns of microbes or plants, recognition of pathogen-derived effectors or colonisation by beneficial microbes. However the process can also be induced by treatment with some natural or synthetic compounds and wounding. The primed mobilization of defence is often associated with development of immunity and stress tolerance. Although the phenomenon has been known for decades, the molecular basis of priming is poorly understood. Here, I summarize recent progress made in unravelling molecular aspects of defence priming that is the accumulation of dormant mitogen-activated protein kinases, chromatin modifications and alterations of primary metabolism. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. The roles of integration in molecular systems biology.

    PubMed

    O'Malley, Maureen A; Soyer, Orkun S

    2012-03-01

    A common way to think about scientific practice involves classifying it as hypothesis- or data-driven. We argue that although such distinctions might illuminate scientific practice very generally, they are not sufficient to understand the day-to-day dynamics of scientific activity and the development of programmes of research. One aspect of everyday scientific practice that is beginning to gain more attention is integration. This paper outlines what is meant by this term and how it has been discussed from scientific and philosophical points of view. We focus on methodological, data and explanatory integration, and show how they are connected. Then, using some examples from molecular systems biology, we will show how integration works in a range of inquiries to generate surprising insights and even new fields of research. From these examples we try to gain a broader perspective on integration in relation to the contexts of inquiry in which it is implemented. In today's environment of data-intensive large-scale science, integration has become both a practical and normative requirement with corresponding implications for meta-methodological accounts of scientific practice. We conclude with a discussion of why an understanding of integration and its dynamics is useful for philosophy of science and scientific practice in general. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Molecular insights into the novel aspects of diatom biology.

    PubMed

    Scala, S; Bowler, C

    2001-10-01

    Diatoms are unicellular photosynthetic eukaryotes that are thought to contribute as much as 25% of global primary productivity. In spite of their ecological importance in the worlds oceans, very little information is available at the molecular level about the novel aspects of their biology. Recent advances, such as the development of gene transfer protocols, are now allowing the genetic dissection of diatom biology. Notable examples are advances in understanding the genetic basis for the silica-based bioinorganic pattern formation of their cell walls and for elucidating key aspects of diatom ecophysiology. The potentiation of current research will allow an evaluation of the use of diatoms to construct submicrometre-scale silicon structures for the nanotechnology industry and will reveal the molecular secrets underlying their ecological success.

  4. Molecular and functional aspects of menstruation in the macaque.

    PubMed

    Brenner, Robert M; Slayden, Ov D

    2012-12-01

    Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

  5. Symbolic programming language in molecular multicenter integral problem

    NASA Astrophysics Data System (ADS)

    Safouhi, Hassan; Bouferguene, Ahmed

    It is well known that in any ab initio molecular orbital (MO) calculation, the major task involves the computation of molecular integrals, among which the computation of three-center nuclear attraction and Coulomb integrals is the most frequently encountered. As the molecular system becomes larger, computation of these integrals becomes one of the most laborious and time-consuming steps in molecular systems calculation. Improvement of the computational methods of molecular integrals would be indispensable to further development in computational studies of large molecular systems. To develop fast and accurate algorithms for the numerical evaluation of these integrals over B functions, we used nonlinear transformations for improving convergence of highly oscillatory integrals. These methods form the basis of new methods for solving various problems that were unsolvable otherwise and have many applications as well. To apply these nonlinear transformations, the integrands should satisfy linear differential equations with coefficients having asymptotic power series in the sense of Poincaré, which in their turn should satisfy some limit conditions. These differential equations are very difficult to obtain explicitly. In the case of molecular integrals, we used a symbolic programming language (MAPLE) to demonstrate that all the conditions required to apply these nonlinear transformation methods are satisfied. Differential equations are obtained explicitly, allowing us to demonstrate that the limit conditions are also satisfied.

  6. Molecular aspects of magnetic resonance imaging and spectroscopy.

    PubMed

    Boesch, C

    1999-01-01

    Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.

  7. Molecular aspects of monoamine oxidase B.

    PubMed

    Ramsay, Rona R

    2016-08-01

    Monoamine oxidases (MAO) influence the monoamine levels in brain by virtue of their role in neurotransmitter breakdown. MAO B is the predominant form in glial cells and in platelets. MAO B structure, function and kinetics are described as a background for the effect of alterations in its activity on behavior. The need to inhibit MAO B to combat decreased brain amines continues to drive the search for new drugs. Reversible and irreversible inhibitors are now designed using data-mining, computational screening, docking and molecular dynamics. Multi-target ligands designed to combat the elevated activity of MAO B in Alzheimer's and Parkinson's Diseases incorporate MAO inhibition (usually irreversible) as well as iron chelation, antioxidant or neuroprotective properties. The main focus of drug design is the catalytic activity of MAO, but the imidazoline I2 site in the entrance cavity of MAO B is also a pharmacological target. Endogenous regulation of MAO B expression is discussed briefly in light of new studies measuring mRNA, protein, or activity in healthy and degenerative samples, including the effect of DNA methylation on the expression. Overall, this review focuses on examples of recent research on the molecular aspects of the expression, activity, and inhibition of MAO B. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Solution of multi-center molecular integrals of Slater-type orbitals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

  9. Environmental Epigenetics and a Unified Theory of the Molecular Aspects of Evolution: A Neo-Lamarckian Concept that Facilitates Neo-Darwinian Evolution.

    PubMed

    Skinner, Michael K

    2015-04-26

    Environment has a critical role in the natural selection process for Darwinian evolution. The primary molecular component currently considered for neo-Darwinian evolution involves genetic alterations and random mutations that generate the phenotypic variation required for natural selection to act. The vast majority of environmental factors cannot directly alter DNA sequence. Epigenetic mechanisms directly regulate genetic processes and can be dramatically altered by environmental factors. Therefore, environmental epigenetics provides a molecular mechanism to directly alter phenotypic variation generationally. Lamarck proposed in 1802 the concept that environment can directly alter phenotype in a heritable manner. Environmental epigenetics and epigenetic transgenerational inheritance provide molecular mechanisms for this process. Therefore, environment can on a molecular level influence the phenotypic variation directly. The ability of environmental epigenetics to alter phenotypic and genotypic variation directly can significantly impact natural selection. Neo-Lamarckian concept can facilitate neo-Darwinian evolution. A unified theory of evolution is presented to describe the integration of environmental epigenetic and genetic aspects of evolution. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. [Migrant workers. The critical aspects of integration].

    PubMed

    Berra, Alessandro

    2011-01-01

    The integration of migrant poplulations with the indigeneous population is regulated by the Italian Decree, D.Lgs 9/7/2003 n. 215 in enforcement of the directive 2000/43/EC implementing the principle of equal treatment between persons irrespective of racial or ethnic origin. The Italian decree, D.Lgs 215/2003, at present in force, according to regulation stipulated as to the equal treatment of diverse cohabiting populations, explicitly forbids any form of discrimination whatsoever, be it direct or indirect. A first description of today's migrant panorama is offered by the Caritas Migrantes and the CNEL (Italian National Council of the Economy of Labour). The most critical aspects on the integration of migrants are described and discussed in the text.

  11. jAMVLE, a New Integrated Molecular Visualization Learning Environment

    ERIC Educational Resources Information Center

    Bottomley, Steven; Chandler, David; Morgan, Eleanor; Helmerhorst, Erik

    2006-01-01

    A new computer-based molecular visualization tool has been developed for teaching, and learning, molecular structure. This java-based jmol Amalgamated Molecular Visualization Learning Environment (jAMVLE) is platform-independent, integrated, and interactive. It has an overall graphical user interface that is intuitive and easy to use. The…

  12. General morphological and biological features of neoplasms: integration of molecular findings.

    PubMed

    Diaz-Cano, S J

    2008-07-01

    This review highlights the importance of morphology-molecular correlations for a proper implementation of new markers. It covers both general aspects of tumorigenesis (which are normally omitted in papers analysing molecular pathways) and the general mechanisms for the acquired capabilities of neoplasms. The mechanisms are also supported by appropriate diagrams for each acquired capability that include overlooked features such as mobilization of cellular resources and changes in chromatin, transcription and epigenetics; fully accepted oncogenes and tumour suppressor genes are highlighted, while the pathways are also presented as activating or inactivating with appropriate colour coding. Finally, the concepts and mechanisms presented enable us to understand the basic requirements for the appropriate implementation of molecular tests in clinical practice. In summary, the basic findings are presented to serve as a bridge to clinical applications. The current definition of neoplasm is descriptive and difficult to apply routinely. Biologically, neoplasms develop through acquisition of capabilities that involve tumour cell aspects and modified microenvironment interactions, resulting in unrestricted growth due to a stepwise accumulation of cooperative genetic alterations that affect key molecular pathways. The correlation of these molecular aspects with morphological changes is essential for better understanding of essential concepts as early neoplasms/precancerous lesions, progression/dedifferentiation, and intratumour heterogeneity. The acquired capabilities include self-maintained replication (cell cycle dysregulation), extended cell survival (cell cycle arrest, apoptosis dysregulation, and replicative lifespan), genetic instability (chromosomal and microsatellite), changes of chromatin, transcription and epigenetics, mobilization of cellular resources, and modified microenvironment interactions (tumour cells, stromal cells, extracellular, endothelium). The acquired

  13. Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems

    DTIC Science & Technology

    2017-08-01

    Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems The views, opinions and/or findings contained in...University of California - San Diego Title: Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems Report Term...including enzymatic reactions , occurring at the aqueous interfaces of thermotropic LCs show promise as the basis of biomolecular triggers of LC

  14. COMPREHENSIVE ASSESSMENT OF COMPLEX TECHNOLOGIES: INTEGRATING VARIOUS ASPECTS IN HEALTH TECHNOLOGY ASSESSMENT.

    PubMed

    Lysdahl, Kristin Bakke; Mozygemba, Kati; Burns, Jacob; Brönneke, Jan Benedikt; Chilcott, James B; Ward, Sue; Hofmann, Bjørn

    2017-01-01

    Despite recent development of health technology assessment (HTA) methods, there are still methodological gaps for the assessment of complex health technologies. The INTEGRATE-HTA guidance for effectiveness, economic, ethical, socio-cultural, and legal aspects, deals with challenges when assessing complex technologies, such as heterogeneous study designs, multiple stakeholder perspectives, and unpredictable outcomes. The objective of this article is to outline this guidance and describe the added value of integrating these assessment aspects. Different methods were used to develop the various parts of the guidance, but all draw on existing, published knowledge and were supported by stakeholder involvement. The guidance was modified after application in a case study and in response to feedback from internal and external reviewers. The guidance consists of five parts, addressing five core aspects of HTA, all presenting stepwise approaches based on the assessment of complexity, context, and stakeholder involvement. The guidance on effectiveness, health economics and ethics aspects focus on helping users choose appropriate, or further develop, existing methods. The recommendations are based on existing methods' applicability for dealing with problems arising with complex interventions. The guidance offers new frameworks to identify socio-cultural and legal issues, along with overviews of relevant methods and sources. The INTEGRATE-HTA guidance outlines a wide range of methods and facilitates appropriate choices among them. The guidance enables understanding of how complexity matters for HTA and brings together assessments from disciplines, such as epidemiology, economics, ethics, law, and social theory. This indicates relevance for a broad range of technologies.

  15. Geometric integration in Born-Oppenheimer molecular dynamics.

    PubMed

    Odell, Anders; Delin, Anna; Johansson, Börje; Cawkwell, Marc J; Niklasson, Anders M N

    2011-12-14

    Geometric integration schemes for extended Lagrangian self-consistent Born-Oppenheimer molecular dynamics, including a weak dissipation to remove numerical noise, are developed and analyzed. The extended Lagrangian framework enables the geometric integration of both the nuclear and electronic degrees of freedom. This provides highly efficient simulations that are stable and energy conserving even under incomplete and approximate self-consistent field (SCF) convergence. We investigate three different geometric integration schemes: (1) regular time reversible Verlet, (2) second order optimal symplectic, and (3) third order optimal symplectic. We look at energy conservation, accuracy, and stability as a function of dissipation, integration time step, and SCF convergence. We find that the inclusion of dissipation in the symplectic integration methods gives an efficient damping of numerical noise or perturbations that otherwise may accumulate from finite arithmetics in a perfect reversible dynamics. © 2011 American Institute of Physics

  16. An integrated molecular cytogenetic map of Cucumis sativus L. chromosome 2.

    PubMed

    Han, Yonghua; Zhang, Zhonghua; Huang, Sanwen; Jin, Weiwei

    2011-01-27

    Integration of molecular, genetic and cytological maps is still a challenge for most plant species. Recent progress in molecular and cytogenetic studies created a basis for developing integrated maps in cucumber (Cucumis sativus L.). In this study, eleven fosmid clones and three plasmids containing 45S rDNA, the centromeric satellite repeat Type III and the pericentriomeric repeat CsRP1 sequences respectively were hybridized to cucumber metaphase chromosomes to assign their cytological location on chromosome 2. Moreover, an integrated molecular cytogenetic map of cucumber chromosomes 2 was constructed by fluorescence in situ hybridization (FISH) mapping of 11 fosmid clones together with the cucumber centromere-specific Type III sequence on meiotic pachytene chromosomes. The cytogenetic map was fully integrated with genetic linkage map since each fosmid clone was anchored by a genetically mapped simple sequence repeat marker (SSR). The relationship between the genetic and physical distances along chromosome was analyzed. Recombination was not evenly distributed along the physical length of chromosome 2. Suppression of recombination was found in centromeric and pericentromeric regions. Our results also indicated that the molecular markers composing the linkage map for chromosome 2 provided excellent coverage of the chromosome.

  17. Making mathematics and science integration happen: key aspects of practice

    NASA Astrophysics Data System (ADS)

    Ríordáin, Máire Ní; Johnston, Jennifer; Walshe, Gráinne

    2016-02-01

    The integration of mathematics and science teaching and learning facilitates student learning, engagement, motivation, problem-solving, criticality and real-life application. However, the actual implementation of an integrative approach to the teaching and learning of both subjects at classroom level, with in-service teachers working collaboratively, at second-level education, is under-researched due to the complexities of school-based research. This study reports on a year-long case study on the implementation of an integrated unit of learning on distance, speed and time, within three second-level schools in Ireland. This study employed a qualitative approach and examined the key aspects of practice that impact on the integration of mathematics and science teaching and learning. We argue that teacher perspective, teacher knowledge of the 'other subject' and of technological pedagogical content knowledge (TPACK), and teacher collaboration and support all impact on the implementation of an integrative approach to mathematics and science education.

  18. Educational aspects of molecular simulation

    NASA Astrophysics Data System (ADS)

    Allen, Michael P.

    This article addresses some aspects of teaching simulation methods to undergraduates and graduate students. Simulation is increasingly a cross-disciplinary activity, which means that the students who need to learn about simulation methods may have widely differing backgrounds. Also, they may have a wide range of views on what constitutes an interesting application of simulation methods. Almost always, a successful simulation course includes an element of practical, hands-on activity: a balance always needs to be struck between treating the simulation software as a 'black box', and becoming bogged down in programming issues. With notebook computers becoming widely available, students often wish to take away the programs to run themselves, and access to raw computer power is not the limiting factor that it once was; on the other hand, the software should be portable and, if possible, free. Examples will be drawn from the author's experience in three different contexts. (1) An annual simulation summer school for graduate students, run by the UK CCP5 organization, in which practical sessions are combined with an intensive programme of lectures describing the methodology. (2) A molecular modelling module, given as part of a doctoral training centre in the Life Sciences at Warwick, for students who might not have a first degree in the physical sciences. (3) An undergraduate module in Physics at Warwick, also taken by students from other disciplines, teaching high performance computing, visualization, and scripting in the context of a physical application such as Monte Carlo simulation.

  19. Glycoprotein Biochemistry (Biosynthesis)--A Vehicle for Teaching Many Aspects of Biochemistry and Molecular Biology.

    ERIC Educational Resources Information Center

    Cole, Clair R.; Smith, Christopher A.

    1990-01-01

    Information about the biosynthesis of the carbohydrate portions or glycans of glycoproteins is presented. The teaching of glycosylation can be used to develop and emphasize many general aspects of biosynthesis, in addition to explaining specific biochemical and molecular biological features associated with producing the oligosaccharide portions of…

  20. Molecular and Cellular Aspects of Calcific Aortic Valve Disease

    PubMed Central

    Towler, Dwight A.

    2014-01-01

    Calcific aortic valve disease (CAVD) increasingly afflicts our aging population. One-third of our elderly have echocardiographic or radiological evidence of aortic valve sclerosis (CAVS), an early and subclinical form of CAVD. Age, gender, tobacco use, hypercholesterolemia, hypertension, and type II diabetes all contribute to the risk of disease that has worldwide distribution. Upon progression to its most severe form --- calcific aortic stenosis (CAS) --- CAVD becomes debilitating and devastating, and 2% of individuals over age 60 suffer from CAS to the extent that surgical intervention is required. No effective pharmacotherapies exist for treating those at risk for clinical progression. It is becoming increasingly apparent that a diverse spectrum of cellular and molecular mechanisms converge to regulate valvular calcium load; this is evidenced not only in histopathologic heterogeneity of CAVD but also from the multiplicity of cell types that can participate in valve biomineralization. In this review, we highlight our current understanding of CAVD disease biology, emphasizing molecular and cellular aspects of its regulation. We end by pointing to important biological and clinical questions that must be answered to enable sophisticated disease staging and the development of new strategies to medically treat CAVD. PMID:23833294

  1. Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome.

    PubMed

    Saeedi Borujeni, Mohammad Javad; Esfandiary, Ebrahim; Taheripak, Gholamreza; Codoñer-Franch, Pilar; Alonso-Iglesias, Eulalia; Mirzaei, Hamed

    2018-02-01

    Diabetes mellitus (DM) is known as one of important common endocrine disorders which could due to deregulation of a variety of cellular and molecular pathways. A large numbers studies indicated that various pathogenesis events including mutation, serin phosphorylation, and increasing/decreasing expression of many genes could contribute to initiation and progression of DM. Insulin resistance is one of important factors which could play critical roles in DM pathogenesis. It has been showed that insulin resistance via targeting a sequence of cellular and molecular pathways (eg, PI3 kinases, PPARγ co-activator-1, microRNAs, serine/threonine kinase Akt, and serin phosphorylation) could induce DM. Among of various factors involved in DM pathogenesis, microRNAs, and exosomes have been emerged as effective factors in initiation and progression of DM. A variety of studies indicated that deregulation of these molecules could change behavior of various types of cells and contribute to progression of DM. Resistin is other main factor which is known as signal molecule involved in insulin resistance. Multiple lines evidence indicated that resistin exerts its effects via affecting on glucose metabolism, inhibition of fatty acid uptake and metabolism with affecting on a variety of targets such as CD36, fatty acid transport protein 1, Acetyl-CoA carboxylase, and AMP-activated protein kinase. Here, we summarized various molecular aspects are associated with DM particularly the molecular pathways involved in insulin resistance and resistin in DM. Moreover, we highlighted exosomes and microRNAs as effective players in initiation and progression of DM. © 2017 Wiley Periodicals, Inc.

  2. Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

    PubMed Central

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L.; Nishihara, Reiko; Tan, Andy S.; Kawachi, Ichiro; Ogino, Shuji

    2015-01-01

    Summary The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations, and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial, and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors, and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference, and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology, and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors, and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging, and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

  3. Integration of molecular pathology, epidemiology and social science for global precision medicine.

    PubMed

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

    2016-01-01

    The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

  4. Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae.

    PubMed Central

    Cid, V J; Durán, A; del Rey, F; Snyder, M P; Nombela, C; Sánchez, M

    1995-01-01

    In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle. PMID:7565410

  5. Molecular aspects of flower senescence and strategies to improve flower longevity

    PubMed Central

    Shibuya, Kenichi

    2018-01-01

    Flower longevity is one of the most important traits for ornamental plants. Ethylene plays a crucial role in flower senescence in some plant species. In several species that show ethylene-dependent flower senescence, genetic modification targeting genes for ethylene biosynthesis or signaling has improved flower longevity. Although little is known about regulatory mechanisms of petal senescence in flowers that show ethylene-independent senescence, a recent study of Japanese morning glory revealed that a NAC transcription factor, EPHEMERAL1 (EPH1), is a key regulator in ethylene-independent petal senescence. EPH1 is induced in an age-dependent manner irrespective of ethylene signal, and suppression of EPH1 expression dramatically delays petal senescence. In ethylene-dependent petal senescence, comprehensive transcriptome analyses revealed the involvement of transcription factors, a basic helix-loop-helix protein and a homeodomain-leucine zipper protein, in the transcriptional regulation of the ethylene biosynthesis enzymes. This review summarizes molecular aspects of flower senescence and discusses strategies to improve flower longevity by molecular breeding. PMID:29681752

  6. Sarcoptes-World Molecular Network (Sarcoptes-WMN): integrating research on scabies.

    PubMed

    Alasaad, Samer; Walton, Shelley; Rossi, Luca; Bornstein, Set; Abu-Madi, Marawan; Soriguer, Ramón C; Fitzgerald, Scott; Zhu, Xing-Quan; Zimmermann, Werner; Ugbomoiko, Uade Samuel; Pei, Kurtis Jai-Chyi; Heukelbach, Jörg

    2011-05-01

    Parasites threaten human and animal health globally. It is estimated that more than 60% of people on planet Earth carry at least one parasite, many of them several different species. Unfortunately, parasite studies suffer from duplications and inconsistencies between different investigator groups. Hence, groups need to collaborate in an integrated manner in areas including parasite control, improved therapy strategies, diagnostic and surveillance tools, and public awareness. Parasite studies will be better served if there is coordinated management of field data and samples across multidisciplinary approach plans, among academic and non-academic organizations worldwide. In this paper we report the first 'Living organism-World Molecular Network', with the cooperation of 167 parasitologists from 88 countries on all continents. This integrative approach, the 'Sarcoptes-World Molecular Network', seeks to harmonize Sarcoptes epidemiology, diagnosis, treatment, and molecular studies from all over the world, with the aim of decreasing mite infestations in humans and animals. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects.

    PubMed

    Bianchin, Marino Muxfeldt; Londero, Renata Gomes; Lima, José Eduardo; Bigal, Marcelo Eduardo

    2010-08-01

    The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.

  8. Engineering aspects of design and integration of ECE diagnostic in ITER

    DOE PAGES

    Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; ...

    2015-03-12

    ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnosticsmore » with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.« less

  9. Quantitative contribution of molecular orbitals to hydrogen bonding in a water dimer: Electron density projected integral (EDPI) analysis

    NASA Astrophysics Data System (ADS)

    Zhang, Zhiyuan; Jiang, Wanrun; Wang, Bo; Wang, Zhigang

    2017-06-01

    We introduce the orbital-resolved electron density projected integral (EDPI) along the H-bond in the real space to quantitatively investigate the specific contribution from the molecular orbitals (MOs) aspect in (H2O)2. Calculation results show that, the electronic occupied orbital (HOMO-4) of (H2O)2 accounts for about surprisingly 40% of the electron density at the bond critical point. Moreover, the electronic density difference analysis visualizes the electron accumulating effect of the orbital interaction within the H-bond between water molecules, supporting its covalent-like character. Our work expands the understanding of H-bond with specific contributions from certain MOs.

  10. Integration of molecular typing results into tuberculosis surveillance in Germany—A pilot study

    PubMed Central

    Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

    2017-01-01

    An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age <15 years (OR = 4.96, 95% CI: 1.69–14.55) and being born in Germany (OR = 2.01, 95% CI: 1.44–2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48–98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It

  11. Integration of molecular typing results into tuberculosis surveillance in Germany-A pilot study.

    PubMed

    Andrés, Marta; Göhring-Zwacka, Elke; Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

    2017-01-01

    An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age <15 years (OR = 4.96, 95% CI: 1.69-14.55) and being born in Germany (OR = 2.01, 95% CI: 1.44-2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48-98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also

  12. Integrating evolutionary and molecular genetics of aging.

    PubMed

    Flatt, Thomas; Schmidt, Paul S

    2009-10-01

    Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.

  13. Hereditary nonpolyposis colorectal cancer: Review of clinical, molecular genetics, and counseling aspects

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

    Bellacosa, A.; Genuardi, M.; Anti, M.

    Lynch syndrome, or hereditary nonpolyposis colon cancer (HNPCC), is an autosomal dominant disease accounting for approximately 1-5% of all colorectal cancer cases. Due to the lack of pathognomonic morphological or biomolecular markers, HNPCC has traditionally posed unique problems to clinicians and geneticists alike, both in terms of diagnosis and clinical management. Recently, novel insight into the pathogenesis of this syndrome has been provided by the identification of its molecular basis. In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development. Mutations in mismatch repair genesmore » lead to an overall increase of the mutation rate and are associated with a phenotype of length instability of microsatellite loci. The present report summarizes the clinicopathological aspects of HNPCC and reviews the most recent molecular and biochemical findings. 115 refs., 2 figs., 3 tabs.« less

  14. Integrating Evolutionary and Molecular Genetics of Aging

    PubMed Central

    Flatt, Thomas; Schmidt, Paul S.

    2010-01-01

    Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940’s and 1950’s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980’s and 1990’s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging. PMID:19619612

  15. Integrating molecular diagnostics into histopathology training: the Belfast model.

    PubMed

    Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

    2014-07-01

    Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Integrated genomic and molecular characterization of cervical cancer.

    PubMed

    2017-03-16

    Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.

  17. Molecular and cellular aspects of rhabdovirus entry.

    PubMed

    Albertini, Aurélie A V; Baquero, Eduard; Ferlin, Anna; Gaudin, Yves

    2012-01-01

    Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell.

  18. Molecular and Cellular Aspects of Rhabdovirus Entry

    PubMed Central

    Albertini, Aurélie A. V.; Baquero, Eduard; Ferlin, Anna; Gaudin, Yves

    2012-01-01

    Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell. PMID:22355455

  19. Lambda Red recombinase-mediated integration of the high molecular weight DNA into the Escherichia coli chromosome.

    PubMed

    Juhas, Mario; Ajioka, James W

    2016-10-05

    Escherichia coli K-12 is a frequently used host for a number of synthetic biology and biotechnology applications and chassis for the development of the minimal cell factories. Novel approaches for integrating high molecular weight DNA into the E. coli chromosome would therefore greatly facilitate engineering efforts in this bacterium. We developed a reliable and flexible lambda Red recombinase-based system, which utilizes overlapping DNA fragments for integration of the high molecular weight DNA into the E. coli chromosome. Our chromosomal integration strategy can be used to integrate high molecular weight DNA of variable length into any non-essential locus in the E. coli chromosome. Using this approach we integrated 15 kb DNA encoding sucrose catabolism and lactose metabolism and transport operons into the fliK locus of the flagellar region 3b in the E. coli K12 MG1655 chromosome. Furthermore, with this system we integrated 50 kb of Bacillus subtilis 168 DNA into two target sites in the E. coli K12 MG1655 chromosome. The chromosomal integrations into the fliK locus occurred with high efficiency, inhibited motility, and did not have a negative effect on the growth of E. coli. In addition to the rational design of synthetic biology devices, our high molecular weight DNA chromosomal integration system will facilitate metabolic and genome-scale engineering of E. coli.

  20. Chemical and molecular aspects on interactions of galanthamine and its derivatives with cholinesterases.

    PubMed

    Gulcan, Hayrettin O; Orhan, Ilkay E; Sener, Bilge

    2015-01-01

    Dual action of galanthamine as potent cholinesterase inhibitor and nicotinic modulator has attracted a great attention to be used in the treatment of AD. Consequently, galanthamine, a natural alkaloid isolated from a Galanthus species (snowdrop, Amaryllidaceae), has become an attractive model compound for synthesis of its novel derivatives to discover new drug candidates. Numerous studies have been done to elucidate interactions between galanthamine and its different derivatives and the enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using in vitro and in silico experimental models. The in vitro studies revealed that galanthamine inhibits AChE in strong, competitive, long-acting, and reversible manner as well as BChE, although its selectivity towards AChE is much higher than BChE. The in silico studies carried out by employing molecular docking experiments as well as molecular dynamics simulations pointed out to existence of strong interactions of galanthamine with the active gorge of AChE, mostly of Torpedo californica (the Pasific electric ray) origin. In this review, we evaluate the mainstays of cholinesterase inhibitory action of galanthamine and its various derivatives from the point of view of chemical and molecular aspects.

  1. Accelerated sampling by infinite swapping of path integral molecular dynamics with surface hopping

    NASA Astrophysics Data System (ADS)

    Lu, Jianfeng; Zhou, Zhennan

    2018-02-01

    To accelerate the thermal equilibrium sampling of multi-level quantum systems, the infinite swapping limit of a recently proposed multi-level ring polymer representation is investigated. In the infinite swapping limit, the ring polymer evolves according to an averaged Hamiltonian with respect to all possible surface index configurations of the ring polymer and thus connects the surface hopping approach to the mean-field path-integral molecular dynamics. A multiscale integrator for the infinite swapping limit is also proposed to enable efficient sampling based on the limiting dynamics. Numerical results demonstrate the huge improvement of sampling efficiency of the infinite swapping compared with the direct simulation of path-integral molecular dynamics with surface hopping.

  2. Vertical resonant tunneling transistors with molecular quantum dots for large-scale integration.

    PubMed

    Hayakawa, Ryoma; Chikyow, Toyohiro; Wakayama, Yutaka

    2017-08-10

    Quantum molecular devices have a potential for the construction of new data processing architectures that cannot be achieved using current complementary metal-oxide-semiconductor (CMOS) technology. The relevant basic quantum transport properties have been examined by specific methods such as scanning probe and break-junction techniques. However, these methodologies are not compatible with current CMOS applications, and the development of practical molecular devices remains a persistent challenge. Here, we demonstrate a new vertical resonant tunneling transistor for large-scale integration. The transistor channel is comprised of a MOS structure with C 60 molecules as quantum dots, and the structure behaves like a double tunnel junction. Notably, the transistors enabled the observation of stepwise drain currents, which originated from resonant tunneling via the discrete molecular orbitals. Applying side-gate voltages produced depletion layers in Si substrates, to achieve effective modulation of the drain currents and obvious peak shifts in the differential conductance curves. Our device configuration thus provides a promising means of integrating molecular functions into future CMOS applications.

  3. Interdisciplinary Education to Integrate Pathology and Epidemiology: Towards Molecular and Population-Level Health Science

    PubMed Central

    Ogino, Shuji; King, Emily E.; Beck, Andrew H.; Sherman, Mark E.; Milner, Danny A.; Giovannucci, Edward

    2012-01-01

    In recent decades, epidemiology, public health, and medical sciences have been increasingly compartmentalized into narrower disciplines. The authors recognize the value of integration of divergent scientific fields in order to create new methods, concepts, paradigms, and knowledge. Herein they describe the recent emergence of molecular pathological epidemiology (MPE), which represents an integration of population and molecular biologic science to gain insights into the etiologies, pathogenesis, evolution, and outcomes of complex multifactorial diseases. Most human diseases, including common cancers (such as breast, lung, prostate, and colorectal cancers, leukemia, and lymphoma) and other chronic diseases (such as diabetes mellitus, cardiovascular diseases, hypertension, autoimmune diseases, psychiatric diseases, and some infectious diseases), are caused by alterations in the genome, epigenome, transcriptome, proteome, metabolome, microbiome, and interactome of all of the above components. In this era of personalized medicine and personalized prevention, we need integrated science (such as MPE) which can decipher diseases at the molecular, genetic, cellular, and population levels simultaneously. The authors believe that convergence and integration of multiple disciplines should be commonplace in research and education. We need to be open-minded and flexible in designing integrated education curricula and training programs for future students, clinicians, practitioners, and investigators. PMID:22935517

  4. Mathematical analysis of the boundary-integral based electrostatics estimation approximation for molecular solvation: exact results for spherical inclusions.

    PubMed

    Bardhan, Jaydeep P; Knepley, Matthew G

    2011-09-28

    We analyze the mathematically rigorous BIBEE (boundary-integral based electrostatics estimation) approximation of the mixed-dielectric continuum model of molecular electrostatics, using the analytically solvable case of a spherical solute containing an arbitrary charge distribution. Our analysis, which builds on Kirkwood's solution using spherical harmonics, clarifies important aspects of the approximation and its relationship to generalized Born models. First, our results suggest a new perspective for analyzing fast electrostatic models: the separation of variables between material properties (the dielectric constants) and geometry (the solute dielectric boundary and charge distribution). Second, we find that the eigenfunctions of the reaction-potential operator are exactly preserved in the BIBEE model for the sphere, which supports the use of this approximation for analyzing charge-charge interactions in molecular binding. Third, a comparison of BIBEE to the recent GBε theory suggests a modified BIBEE model capable of predicting electrostatic solvation free energies to within 4% of a full numerical Poisson calculation. This modified model leads to a projection-framework understanding of BIBEE and suggests opportunities for future improvements. © 2011 American Institute of Physics

  5. Integrative pathway knowledge bases as a tool for systems molecular medicine.

    PubMed

    Liang, Mingyu

    2007-08-20

    There exists a sense of urgency to begin to generate a cohesive assembly of biomedical knowledge as the pace of knowledge accumulation accelerates. The urgency is in part driven by the emergence of systems molecular medicine that emphasizes the combination of systems analysis and molecular dissection in the future of medical practice and research. A potentially powerful approach is to build integrative pathway knowledge bases that link organ systems function with molecules.

  6. 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

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

    PubMed Central

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

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

  8. Path integral molecular dynamic simulation of flexible molecular systems in their ground state: Application to the water dimer

    NASA Astrophysics Data System (ADS)

    Schmidt, Matthew; Roy, Pierre-Nicholas

    2018-03-01

    We extend the Langevin equation Path Integral Ground State (LePIGS), a ground state quantum molecular dynamics method, to simulate flexible molecular systems and calculate both energetic and structural properties. We test the approach with the H2O and D2O monomers and dimers. We systematically optimize all simulation parameters and use a unity trial wavefunction. We report ground state energies, dissociation energies, and structural properties using three different water models, two of which are empirically based, q-TIP4P/F and q-SPC/Fw, and one which is ab initio, MB-pol. We demonstrate that our energies calculated from LePIGS can be merged seamlessly with low temperature path integral molecular dynamics calculations and note the similarities between the two methods. We also benchmark our energies against previous diffusion Monte Carlo calculations using the same potentials and compare to experimental results. We further demonstrate that accurate vibrational energies of the H2O and D2O monomer can be calculated from imaginary time correlation functions generated from the LePIGS simulations using solely the unity trial wavefunction.

  9. Integrative Systems Biology for Data Driven Knowledge Discovery

    PubMed Central

    Greene, Casey S.; Troyanskaya, Olga G.

    2015-01-01

    Integrative systems biology is an approach that brings together diverse high throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost effective manner. Using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of yet unknown components of a system of interest and how its malfunction leads to disease. PMID:21044756

  10. i-PI: A Python interface for ab initio path integral molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Ceriotti, Michele; More, Joshua; Manolopoulos, David E.

    2014-03-01

    Recent developments in path integral methodology have significantly reduced the computational expense of including quantum mechanical effects in the nuclear motion in ab initio molecular dynamics simulations. However, the implementation of these developments requires a considerable programming effort, which has hindered their adoption. Here we describe i-PI, an interface written in Python that has been designed to minimise the effort required to bring state-of-the-art path integral techniques to an electronic structure program. While it is best suited to first principles calculations and path integral molecular dynamics, i-PI can also be used to perform classical molecular dynamics simulations, and can just as easily be interfaced with an empirical forcefield code. To give just one example of the many potential applications of the interface, we use it in conjunction with the CP2K electronic structure package to showcase the importance of nuclear quantum effects in high-pressure water. Catalogue identifier: AERN_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AERN_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 138626 No. of bytes in distributed program, including test data, etc.: 3128618 Distribution format: tar.gz Programming language: Python. Computer: Multiple architectures. Operating system: Linux, Mac OSX, Windows. RAM: Less than 256 Mb Classification: 7.7. External routines: NumPy Nature of problem: Bringing the latest developments in the modelling of nuclear quantum effects with path integral molecular dynamics to ab initio electronic structure programs with minimal implementational effort. Solution method: State-of-the-art path integral molecular dynamics techniques are implemented in a Python interface. Any electronic structure code can be patched to receive the atomic

  11. Integrated molecular portrait of non-small cell lung cancers

    PubMed Central

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Results At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944. Conclusions Integrated molecular characterization of AC and SCC helped identify clinically relevant markers

  12. Fabrication of reproducible, integration-compatible hybrid molecular/si electronics.

    PubMed

    Yu, Xi; Lovrinčić, Robert; Kraynis, Olga; Man, Gabriel; Ely, Tal; Zohar, Arava; Toledano, Tal; Cahen, David; Vilan, Ayelet

    2014-12-29

    Reproducible molecular junctions can be integrated within standard CMOS technology. Metal-molecule-semiconductor junctions are fabricated by direct Si-C binding of hexadecane or methyl-styrene onto oxide-free H-Si(111) surfaces, with the lateral size of the junctions defined by an etched SiO2 well and with evaporated Pb as the top contact. The current density, J, is highly reproducible with a standard deviation in log(J) of 0.2 over a junction diameter change from 3 to 100 μm. Reproducibility over such a large range indicates that transport is truly across the molecules and does not result from artifacts like edge effects or defects in the molecular monolayer. Device fabrication is tested for two n-Si doping levels. With highly doped Si, transport is dominated by tunneling and reveals sharp conductance onsets at room temperature. Using the temperature dependence of current across medium-doped n-Si, the molecular tunneling barrier can be separated from the Si-Schottky one, which is a 0.47 eV, in agreement with the molecular-modified surface dipole and quite different from the bare Si-H junction. This indicates that Pb evaporation does not cause significant chemical changes to the molecules. The ability to manufacture reliable devices constitutes important progress toward possible future hybrid Si-based molecular electronics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Host-Guest Chemistry in Integrated Porous Space Formed by Molecular Self-Assembly at Liquid-Solid Interfaces.

    PubMed

    Iritani, Kohei; Tahara, Kazukuni; De Feyter, Steven; Tobe, Yoshito

    2017-05-16

    Host-guest chemistry in two-dimensional (2D) space, that is, physisorbed monolayers of a single atom or a single molecular thickness on surfaces, has become a subject of intense current interest because of perspectives for various applications in molecular-scale electronics, selective sensors, and tailored catalysis. Scanning tunneling microscopy has been used as a powerful tool for the visualization of molecules in real space on a conducting substrate surface. For more than a decade, we have been investigating the self-assembly of a series of triangle-shaped phenylene-ethynylene macrocycles called dehydrobenzo[12]annulenes (DBAs). These molecules are substituted with six alkyl chains and are capable of forming hexagonal porous 2D molecular networks via van der Waals interactions between interdigitated alkyl chains at the interface of organic solvents and graphite. The dimension of the nanoporous space or nanowell formed by the self-assembly of DBAs can be controlled from 1.6 to 4.7 nm by simply changing the alkyl chain length from C 6 to C 20 . Single molecules as well as homoclusters and heteroclusters are capable of coadsorbing within the host matrix using shape- and size-complementarity principles. Moreover, on the basis of the versatility of the DBA molecules that allows chemical modification of the alkyl chain terminals, we were able to decorate the interior space of the nanoporous networks with functional groups such as azobenzenedicarboxylic acid for photoresponsive guest adsorption/desorption or fluoroalkanes and tetraethylene glycol groups for selective guest binding by electrostatic interactions and zinc-porphyrin units for complexation with a guest by charge-transfer interactions. In this Feature Article, we describe the general aspects of molecular self-assembly at liquid/solid interfaces, followed by the formation of programmed porous molecular networks using rationally designed molecular building blocks. We focus on our own work involving host

  14. AceCloud: Molecular Dynamics Simulations in the Cloud.

    PubMed

    Harvey, M J; De Fabritiis, G

    2015-05-26

    We present AceCloud, an on-demand service for molecular dynamics simulations. AceCloud is designed to facilitate the secure execution of large ensembles of simulations on an external cloud computing service (currently Amazon Web Services). The AceCloud client, integrated into the ACEMD molecular dynamics package, provides an easy-to-use interface that abstracts all aspects of interaction with the cloud services. This gives the user the experience that all simulations are running on their local machine, minimizing the learning curve typically associated with the transition to using high performance computing services.

  15. Building muscle: molecular regulation of myogenesis.

    PubMed

    Bentzinger, C Florian; Wang, Yu Xin; Rudnicki, Michael A

    2012-02-01

    The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks.

  16. Goals and objectives for molecular pathology education in residency programs. The Association for Molecular Pathology Training and Education Committee.

    PubMed

    1999-11-01

    Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized.

  17. Integrating multiple molecular sources into a clinical risk prediction signature by extracting complementary information.

    PubMed

    Hieke, Stefanie; Benner, Axel; Schlenl, Richard F; Schumacher, Martin; Bullinger, Lars; Binder, Harald

    2016-08-30

    High-throughput technology allows for genome-wide measurements at different molecular levels for the same patient, e.g. single nucleotide polymorphisms (SNPs) and gene expression. Correspondingly, it might be beneficial to also integrate complementary information from different molecular levels when building multivariable risk prediction models for a clinical endpoint, such as treatment response or survival. Unfortunately, such a high-dimensional modeling task will often be complicated by a limited overlap of molecular measurements at different levels between patients, i.e. measurements from all molecular levels are available only for a smaller proportion of patients. We propose a sequential strategy for building clinical risk prediction models that integrate genome-wide measurements from two molecular levels in a complementary way. To deal with partial overlap, we develop an imputation approach that allows us to use all available data. This approach is investigated in two acute myeloid leukemia applications combining gene expression with either SNP or DNA methylation data. After obtaining a sparse risk prediction signature e.g. from SNP data, an automatically selected set of prognostic SNPs, by componentwise likelihood-based boosting, imputation is performed for the corresponding linear predictor by a linking model that incorporates e.g. gene expression measurements. The imputed linear predictor is then used for adjustment when building a prognostic signature from the gene expression data. For evaluation, we consider stability, as quantified by inclusion frequencies across resampling data sets. Despite an extremely small overlap in the application example with gene expression and SNPs, several genes are seen to be more stably identified when taking the (imputed) linear predictor from the SNP data into account. In the application with gene expression and DNA methylation, prediction performance with respect to survival also indicates that the proposed approach might

  18. Preface: Special Topic on Frontiers in Molecular Scale Electronics

    NASA Astrophysics Data System (ADS)

    Evers, Ferdinand; Venkataraman, Latha

    2017-03-01

    The electronic, mechanical, and thermoelectric properties of molecular scale devices have fascinated scientists across several disciplines in natural sciences and engineering. The interest is partially technological, driven by the fast miniaturization of integrated circuits that now have reached characteristic features at the nanometer scale. Equally important, a very strong incentive also exists to elucidate the fundamental aspects of structure-function relations for nanoscale devices, which utilize molecular building blocks as functional units. Thus motivated, a rich research field has established itself, broadly termed "Molecular Electronics," that hosts a plethora of activities devoted to this goal in chemistry, physics, and electrical engineering. This Special Topic on Frontiers of Molecular Scale Electronics captures recent theoretical and experimental advances in the field.

  19. Integrating the epistemic and ontological aspects of content knowledge in science teaching and learning

    NASA Astrophysics Data System (ADS)

    Papadouris, Nicos; Constantinou, Constantinos P.

    2017-04-01

    Promoting facility with content knowledge is one of the most important objectives of science teaching. Conventionally, the focus for this objective is placed on the substantive side of content knowledge (e.g. science concepts/laws), whereas its epistemic or ontological aspects (e.g. why do we construct concepts?) rarely receive explicit attention. In this article, we develop a theoretical argument for the value of elevating the attention paid to the epistemic/ontological aspects of content knowledge and integrating them with its substantive side. Our argument is structured in two parts. The first unpacks the epistemic/ontological aspects of content knowledge and their role in science. For this, we focus on two specific aspects (i.e. ontological status and epistemic value of science concepts), which we elaborate in the context of two particular content domains, namely magnetism and energy. The second part of the argument highlights the potential of discourse on epistemic/ontological aspects to facilitate learning in science. We delineate how such discourse could (a) promote coherent conceptual understanding, (b) foster a productive epistemological stance towards science learning, and (c) enhance students' appreciation of ideas associated with the nature of science. The article concludes with a discussion of ensuing implications for science education.

  20. Molecular simulation aspects of amyloid peptides at membrane interface.

    PubMed

    Liu, Yonglan; Ren, Baiping; Zhang, Yanxian; Sun, Yan; Chang, Yung; Liang, Guizhao; Xu, Lijian; Zheng, Jie

    2018-02-06

    The interactions of amyloid peptides with cell membranes play an important role in maintaining the integrity and functionality of cell membrane. A thorough molecular-level understanding of the structure, dynamics, and interactions between amyloid peptides and cell membranes is critical to amyloid aggregation and toxicity mechanisms for the bench-to-bedside applications. Here we review the most recent computational studies of amyloid peptides at model cell membranes. Different mechanisms of action of amyloid peptides on/in cell membranes, targeted by different computational techniques at different lengthscales and timescales, are rationally discussed. Finally, we have proposed some new insights into the remaining challenges and perspectives for future studies to improve our understanding of the activity of amyloid peptides associated with protein-misfolding diseases. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Numerical solution of boundary-integral equations for molecular electrostatics.

    PubMed

    Bardhan, Jaydeep P

    2009-03-07

    Numerous molecular processes, such as ion permeation through channel proteins, are governed by relatively small changes in energetics. As a result, theoretical investigations of these processes require accurate numerical methods. In the present paper, we evaluate the accuracy of two approaches to simulating boundary-integral equations for continuum models of the electrostatics of solvation. The analysis emphasizes boundary-element method simulations of the integral-equation formulation known as the apparent-surface-charge (ASC) method or polarizable-continuum model (PCM). In many numerical implementations of the ASC/PCM model, one forces the integral equation to be satisfied exactly at a set of discrete points on the boundary. We demonstrate in this paper that this approach to discretization, known as point collocation, is significantly less accurate than an alternative approach known as qualocation. Furthermore, the qualocation method offers this improvement in accuracy without increasing simulation time. Numerical examples demonstrate that electrostatic part of the solvation free energy, when calculated using the collocation and qualocation methods, can differ significantly; for a polypeptide, the answers can differ by as much as 10 kcal/mol (approximately 4% of the total electrostatic contribution to solvation). The applicability of the qualocation discretization to other integral-equation formulations is also discussed, and two equivalences between integral-equation methods are derived.

  2. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

    PubMed

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude; Newton, Yulia; Shih, Juliann; Robertson, A Gordon; Hinoue, Toshinori; Hoadley, Katherine A; Gibb, Ewan A; Roszik, Jason; Covington, Kyle R; Wu, Chia-Chin; Shinbrot, Eve; Stransky, Nicolas; Hegde, Apurva; Yang, Ju Dong; Reznik, Ed; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I; Hess, Julian M; Auman, J Todd; Rhie, Suhn K; Bowlby, Reanne; Borad, Mitesh J; Zhu, Andrew X; Stuart, Josh M; Sander, Chris; Akbani, Rehan; Cherniack, Andrew D; Deshpande, Vikram; Mounajjed, Taofic; Foo, Wai Chin; Torbenson, Michael S; Kleiner, David E; Laird, Peter W; Wheeler, David A; McRee, Autumn J; Bathe, Oliver F; Andersen, Jesper B; Bardeesy, Nabeel; Roberts, Lewis R; Kwong, Lawrence N

    2017-03-14

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Optical biosensor technologies for molecular diagnostics at the point-of-care

    NASA Astrophysics Data System (ADS)

    Schotter, Joerg; Schrittwieser, Stefan; Muellner, Paul; Melnik, Eva; Hainberger, Rainer; Koppitsch, Guenther; Schrank, Franz; Soulantika, Katerina; Lentijo-Mozo, Sergio; Pelaz, Beatriz; Parak, Wolfgang; Ludwig, Frank; Dieckhoff, Jan

    2015-05-01

    Label-free optical schemes for molecular biosensing hold a strong promise for point-of-care applications in medical research and diagnostics. Apart from diagnostic requirements in terms of sensitivity, specificity, and multiplexing capability, also other aspects such as ease of use and manufacturability have to be considered in order to pave the way to a practical implementation. We present integrated optical waveguide as well as magnetic nanoparticle based molecular biosensor concepts that address these aspects. The integrated optical waveguide devices are based on low-loss photonic wires made of silicon nitride deposited by a CMOS compatible plasma-enhanced chemical vapor deposition (PECVD) process that allows for backend integration of waveguides on optoelectronic CMOS chips. The molecular detection principle relies on evanescent wave sensing in the 0.85 μm wavelength regime by means of Mach-Zehnder interferometers, which enables on-chip integration of silicon photodiodes and, thus, the realization of system-on-chip solutions. Our nanoparticle-based approach is based on optical observation of the dynamic response of functionalized magneticcore/ noble-metal-shell nanorods (`nanoprobes') to an externally applied time-varying magnetic field. As target molecules specifically bind to the surface of the nanoprobes, the observed dynamics of the nanoprobes changes, and the concentration of target molecules in the sample solution can be quantified. This approach is suitable for dynamic real-time measurements and only requires minimal sample preparation, thus presenting a highly promising point-of-care diagnostic system. In this paper, we present a prototype of a diagnostic device suitable for highly automated sample analysis by our nanoparticle-based approach.

  4. Respiromics - An integrative analysis linking mitochondrial bioenergetics to molecular signatures.

    PubMed

    Walheim, Ellen; Wiśniewski, Jacek R; Jastroch, Martin

    2018-03-01

    Energy metabolism is challenged upon nutrient stress, eventually leading to a variety of metabolic diseases that represent a major global health burden. Here, we combine quantitative mitochondrial respirometry (Seahorse technology) and proteomics (LC-MS/MS-based total protein approach) to understand how molecular changes translate to changes in mitochondrial energy transduction during diet-induced obesity (DIO) in the liver. The integrative analysis reveals that significantly increased palmitoyl-carnitine respiration is supported by an array of proteins enriching lipid metabolism pathways. Upstream of the respiratory chain, the increased capacity for ATP synthesis during DIO associates strongest to mitochondrial uptake of pyruvate, which is routed towards carboxylation. At the respiratory chain, robust increases of complex I are uncovered by cumulative analysis of single subunit concentrations. Specifically, nuclear-encoded accessory subunits, but not mitochondrial-encoded or core units, appear to be permissive for enhanced lipid oxidation. Our integrative analysis, that we dubbed "respiromics", represents an effective tool to link molecular changes to functional mechanisms in liver energy metabolism, and, more generally, can be applied for mitochondrial analysis in a variety of metabolic and mitochondrial disease models. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

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

    PubMed

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

    2009-10-15

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

  6. Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

    PubMed

    Papadakis, G; Friedt, J M; Eck, M; Rabus, D; Jobst, G; Gizeli, E

    2017-09-01

    The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

  7. Integrated Molecular Characterization of Testicular Germ Cell Tumors.

    PubMed

    Shen, Hui; Shih, Juliann; Hollern, Daniel P; Wang, Linghua; Bowlby, Reanne; Tickoo, Satish K; Thorsson, Vésteinn; Mungall, Andrew J; Newton, Yulia; Hegde, Apurva M; Armenia, Joshua; Sánchez-Vega, Francisco; Pluta, John; Pyle, Louise C; Mehra, Rohit; Reuter, Victor E; Godoy, Guilherme; Jones, Jeffrey; Shelley, Carl S; Feldman, Darren R; Vidal, Daniel O; Lessel, Davor; Kulis, Tomislav; Cárcano, Flavio M; Leraas, Kristen M; Lichtenberg, Tara M; Brooks, Denise; Cherniack, Andrew D; Cho, Juok; Heiman, David I; Kasaian, Katayoon; Liu, Minwei; Noble, Michael S; Xi, Liu; Zhang, Hailei; Zhou, Wanding; ZenKlusen, Jean C; Hutter, Carolyn M; Felau, Ina; Zhang, Jiashan; Schultz, Nikolaus; Getz, Gad; Meyerson, Matthew; Stuart, Joshua M; Akbani, Rehan; Wheeler, David A; Laird, Peter W; Nathanson, Katherine L; Cortessis, Victoria K; Hoadley, Katherine A

    2018-06-12

    We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Organisational Learning and the Organisational Life Cycle: The Differential Aspects of an Integrated Relationship in SMEs

    ERIC Educational Resources Information Center

    Tam, Steven; Gray, David E.

    2016-01-01

    Purpose: The purpose of this study is to relate the practice of organisational learning in small- and medium-sized enterprises (SMEs) to the organisational life cycle (OLC), contextualising the differential aspects of an integrated relationship between them. Design/methodology/approach: It is a mixed-method study with two consecutive phases. In…

  9. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    PubMed

    Santiago, Jose A; Potashkin, Judith A

    2013-01-01

    Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that

  10. Molecular radiotherapy: the NUKFIT software for calculating the time-integrated activity coefficient.

    PubMed

    Kletting, P; Schimmel, S; Kestler, H A; Hänscheid, H; Luster, M; Fernández, M; Bröer, J H; Nosske, D; Lassmann, M; Glatting, G

    2013-10-01

    Calculation of the time-integrated activity coefficient (residence time) is a crucial step in dosimetry for molecular radiotherapy. However, available software is deficient in that it is either not tailored for the use in molecular radiotherapy and/or does not include all required estimation methods. The aim of this work was therefore the development and programming of an algorithm which allows for an objective and reproducible determination of the time-integrated activity coefficient and its standard error. The algorithm includes the selection of a set of fitting functions from predefined sums of exponentials and the choice of an error model for the used data. To estimate the values of the adjustable parameters an objective function, depending on the data, the parameters of the error model, the fitting function and (if required and available) Bayesian information, is minimized. To increase reproducibility and user-friendliness the starting values are automatically determined using a combination of curve stripping and random search. Visual inspection, the coefficient of determination, the standard error of the fitted parameters, and the correlation matrix are provided to evaluate the quality of the fit. The functions which are most supported by the data are determined using the corrected Akaike information criterion. The time-integrated activity coefficient is estimated by analytically integrating the fitted functions. Its standard error is determined assuming Gaussian error propagation. The software was implemented using MATLAB. To validate the proper implementation of the objective function and the fit functions, the results of NUKFIT and SAAM numerical, a commercially available software tool, were compared. The automatic search for starting values was successfully tested for reproducibility. The quality criteria applied in conjunction with the Akaike information criterion allowed the selection of suitable functions. Function fit parameters and their standard

  11. Toward an integrative molecular approach to wildlife disease.

    PubMed

    DeCandia, Alexandra L; Dobson, Andrew P; vonHoldt, Bridgett M

    2018-01-29

    Pathogens pose serious threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks. As such, wildlife managers are often tasked with mitigating the negative effects of disease. Yet, parasites form a major component of biodiversity that often persist. This is due to logistical challenges of implementing management strategies and to insufficient understanding of host-parasite dynamics. We advocate for an inclusive understanding of molecular diversity in driving parasite infection and variable host disease states in wildlife systems. More specifically, we examine the roles of genetic, epigenetic, and commensal microbial variation in disease pathogenesis. These include mechanisms underlying parasite virulence and host resistance and tolerance, and the development, regulation, and parasite subversion of immune pathways, among other processes. Case studies of devil facial tumor disease in Tasmanian devils (Sarcophilus harrisii) and chytridiomycosis in globally distributed amphibians exemplify the broad range of questions that can be addressed by examining different facets of molecular diversity. For particularly complex systems, integrative molecular analyses present a promising frontier that can provide critical insights necessary to elucidate disease dynamics operating across scales. These insights enable more accurate risk assessment, reconstruction of transmission pathways, discernment of optimal intervention strategies, and development of more effective and ecologically sound treatments that minimize damage to the host population and environment. Such measures are crucial when mitigating threats posed by wildlife disease to humans, domestic animals, and species of conservation concern. © 2018 Society for Conservation Biology.

  12. Modeling Molecular and Cellular Aspects of Human Disease using the Nematode Caenorhabditis elegans

    PubMed Central

    Silverman, Gary A.; Luke, Cliff J.; Bhatia, Sangeeta R.; Long, Olivia S.; Vetica, Anne C.; Perlmutter, David H.; Pak, Stephen C.

    2009-01-01

    As an experimental system, Caenorhabditis elegans, offers a unique opportunity to interrogate in vivo the genetic and molecular functions of human disease-related genes. For example, C. elegans has provided crucial insights into fundamental biological processes such as cell death and cell fate determinations, as well as pathological processes such as neurodegeneration and microbial susceptibility. The C. elegans model has several distinct advantages including a completely sequenced genome that shares extensive homology with that of mammals, ease of cultivation and storage, a relatively short lifespan and techniques for generating null and transgenic animals. However, the ability to conduct unbiased forward and reverse genetic screens in C. elegans remains one of the most powerful experimental paradigms for discovering the biochemical pathways underlying human disease phenotypes. The identification of these pathways leads to a better understanding of the molecular interactions that perturb cellular physiology, and forms the foundation for designing mechanism-based therapies. To this end, the ability to process large numbers of isogenic animals through automated work stations suggests that C. elegans, manifesting different aspects of human disease phenotypes, will become the platform of choice for in vivo drug discovery and target validation using high-throughput/content screening technologies. PMID:18852689

  13. SpectraPlot.com: Integrated spectroscopic modeling of atomic and molecular gases

    NASA Astrophysics Data System (ADS)

    Goldenstein, Christopher S.; Miller, Victor A.; Mitchell Spearrin, R.; Strand, Christopher L.

    2017-10-01

    SpectraPlot is a web-based application for simulating spectra of atomic and molecular gases. At the time this manuscript was written, SpectraPlot consisted of four primary tools for calculating: (1) atomic and molecular absorption spectra, (2) atomic and molecular emission spectra, (3) transition linestrengths, and (4) blackbody emission spectra. These tools currently employ the NIST ASD, HITRAN2012, and HITEMP2010 databases to perform line-by-line simulations of spectra. SpectraPlot employs a modular, integrated architecture, enabling multiple simulations across multiple databases and/or thermodynamic conditions to be visualized in an interactive plot window. The primary objective of this paper is to describe the architecture and spectroscopic models employed by SpectraPlot in order to provide its users with the knowledge required to understand the capabilities and limitations of simulations performed using SpectraPlot. Further, this manuscript discusses the accuracy of several underlying approximations used to decrease computational time, in particular, the use of far-wing cutoff criteria.

  14. Variational path integral molecular dynamics and hybrid Monte Carlo algorithms using a fourth order propagator with applications to molecular systems

    NASA Astrophysics Data System (ADS)

    Kamibayashi, Yuki; Miura, Shinichi

    2016-08-01

    In the present study, variational path integral molecular dynamics and associated hybrid Monte Carlo (HMC) methods have been developed on the basis of a fourth order approximation of a density operator. To reveal various parameter dependence of physical quantities, we analytically solve one dimensional harmonic oscillators by the variational path integral; as a byproduct, we obtain the analytical expression of the discretized density matrix using the fourth order approximation for the oscillators. Then, we apply our methods to realistic systems like a water molecule and a para-hydrogen cluster. In the HMC, we adopt two level description to avoid the time consuming Hessian evaluation. For the systems examined in this paper, the HMC method is found to be about three times more efficient than the molecular dynamics method if appropriate HMC parameters are adopted; the advantage of the HMC method is suggested to be more evident for systems described by many body interaction.

  15. 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

  16. Goals and Objectives for Molecular Pathology Education in Residency Programs

    PubMed Central

    1999-01-01

    Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized. PMID:11272908

  17. Cellular and molecular aspects of rhabdovirus interactions with insect and plant hosts.

    PubMed

    Ammar, El-Desouky; Tsai, Chi-Wei; Whitfield, Anna E; Redinbaugh, Margaret G; Hogenhout, Saskia A

    2009-01-01

    The rhabdoviruses form a large family (Rhabdoviridae) whose host ranges include humans, other vertebrates, invertebrates, and plants. There are at least 90 plant-infecting rhabdoviruses, several of which are economically important pathogens of various crops. All definitive plant-infecting and many vertebrate-infecting rhabdoviruses are persistently transmitted by insect vectors, and a few putative plant rhabdoviruses are transmitted by mites. Plant rhabdoviruses replicate in their plant and arthropod hosts, and transmission by vectors is highly specific, with each virus species transmitted by one or a few related insect species, mainly aphids, leafhoppers, or planthoppers. Here, we provide an overview of plant rhabdovirus interactions with their insect hosts and of how these interactions compare with those of vertebrate-infecting viruses and with the Sigma rhabdovirus that infects Drosophila flies. We focus on cellular and molecular aspects of vector/host specificity, transmission barriers, and virus receptors in the vectors. In addition, we briefly discuss recent advances in understanding rhabdovirus-plant interactions.

  18. Urban green valuation integrating biophysical and qualitative aspects.

    PubMed

    Lang, Stefan

    2018-01-01

    Urban green mapping has become an operational task in city planning, urban land management, and quality of life assessments. As a multi-dimensional, integrative concept, urban green comprising several ecological, socio-economic, and policy-related aspects. In this paper, the author advances the representation of urban green by deriving scale-adapted, policy-relevant units. These so-called geons represent areas of uniform green valuation under certain size and homogeneity constraints in a spatially explicit representation. The study accompanies a regular monitoring scheme carried out by the urban municipality of the city of Salzburg, Austria, using optical satellite data. It was conducted in two stages, namely SBG_QB (10.2 km², QuickBird data from 2005) and SBG_WV (140 km², WorldView-2 data from 2010), within the functional urban area of Salzburg. The geon delineation was validated by several quantitative measures and spatial analysis techniques, as well as ground documentation, including panorama photographs and visual interpretation. The spatial association pattern was assessed by calculating Global Moran's I with incremental search distances. The final geonscape, consisting of 1083 units with an average size of 13.5 ha, was analyzed by spatial metrics. Finally, categories were derived for different types of functional geons. Future research paths and improvements to the described strategy are outlined.

  19. High throughput gene expression profiling: a molecular approach to integrative physiology

    PubMed Central

    Liang, Mingyu; Cowley, Allen W; Greene, Andrew S

    2004-01-01

    Integrative physiology emphasizes the importance of understanding multiple pathways with overlapping, complementary, or opposing effects and their interactions in the context of intact organisms. The DNA microarray technology, the most commonly used method for high-throughput gene expression profiling, has been touted as an integrative tool that provides insights into regulatory pathways. However, the physiology community has been slow in acceptance of these techniques because of early failure in generating useful data and the lack of a cohesive theoretical framework in which experiments can be analysed. With recent advances in both technology and analysis, we propose a concept of multidimensional integration of physiology that incorporates data generated by DNA microarray and other functional, genomic, and proteomic approaches to achieve a truly integrative understanding of physiology. Analysis of several studies performed in simpler organisms or in mammalian model animals supports the feasibility of such multidimensional integration and demonstrates the power of DNA microarray as an indispensable molecular tool for such integration. Evaluation of DNA microarray techniques indicates that these techniques, despite limitations, have advanced to a point where the question-driven profiling research has become a feasible complement to the conventional, hypothesis-driven research. With a keen sense of homeostasis, global regulation, and quantitative analysis, integrative physiologists are uniquely positioned to apply these techniques to enhance the understanding of complex physiological functions. PMID:14678487

  20. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors

    NASA Astrophysics Data System (ADS)

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T.; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  1. Monolithic integration of multiple wavelength vertical-cavity surface-emitting lasers by mask molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Saito, Hideaki; Ogura, Ichiro; Sugimoto, Yoshimasa; Kasahara, Kenichi

    1995-05-01

    The monolithic incorporation and performance of vertical-cavity surface-emitting lasers (VCSELs) emitting at two distinct wavelengths, which were suited for application to wavelength division multiplexing (WDM) systems were reported. The monolithic integration of two-wavelength VCSEL arrays was achieved by using mask molecular beam epitaxy. This method can generate arrays that have the desired integration area size and wavelength separation.

  2. Psychological aspects of patients with intestinal stoma: integrative review 1

    PubMed Central

    Silva, Natália Michelato; dos Santos, Manoel Antônio; Rosado, Sara Rodrigues; Galvão, Cristina Maria; Sonobe, Helena Megumi

    2017-01-01

    ABSTRACT Objective: to analyze evidences of psychological aspects of patients with intestinal stoma. Method: integrative review with search of primary studies in the PsycINFO, PubMed, CINAHL and WOS databases and in the SciELO periodicals portal. Inclusion criteria were: primary studies published in a ten-year period, in Portuguese, Spanish or English, available in full length and addressing the theme of the review. Results: after analytical reading, 27 primary studies were selected and results pointed out the need to approach patients before surgery to prevent the complications, anxieties and fears generated by the stoma. The national and international scientific production on the experience of stomized patients in the perioperative moments is scarce. Conclusion: it is recomendable that health professionals invest in research on interventions aimed at the main psychological demands of stomized patients in the perioperative period, respecting their autonomy on the decisions to be made regarding their health/illness state and treatments. PMID:29236836

  3. Cellular and molecular aspects of plant adaptation to microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth; Kozeko, Liudmyla

    2016-07-01

    Elucidation of the range and mechanisms of the biological effects of microgravity is one of the urgent fundamental tasks of space and gravitational biology. The absence of forbidding on plant growth and development in orbital flight allows studying different aspects of plant adaptation to this factor that is directly connected with development of the technologies of bioregenerative life-support systems. Microgravity belongs to the environmental factors which cause adaptive reactions at the cellular and molecular levels in the range of physiological responses in the framework of genetically determined program of ontogenesis. It is known that cells of a multicellular organism not only take part in reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and molecular levels in real and simulated microgravity is considered. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in the cell organelle functional load. The maintenance of the plasmalemma fluidity at the certain level, an activation of both the antioxidant system and expression of HSP genes, especially HSP70, under increasing reactive oxygen species, lipid peroxidation intensity and alteration in protein homeostasis, are a strategic paradigm of rapid (primary) cell adaptation to microgravity. In this sense, biological membranes, especially plasmalemma, and their properties and functions may be considered as the most sensitive indicators of the influence of gravity or altered gravity on a cell. The plasmalemma lipid bilayer is a border between the cell internal content and environment, so it is a mediator

  4. Therapeutic, Molecular and Computational Aspects of Novel Monoamine Oxidase (MAO) Inhibitors.

    PubMed

    Ramesh, Muthusamy; Dokurugu, Yussif M; Thompson, Michael D; Soliman, Mahmoud E

    2017-01-01

    Background Due to the limited number of MAO inhibitors in the clinics, several research efforts are aimed at the discovery of novel MAO inhibitors. At present, a high specificity and a reversible mode of inhibition of MAO-A/B are cited as desirable traits in drug discovery process. This will help to reduce the probability of causing target disruption and may increase the duration of action of drug. Most of the existing MAO inhibitors lead to side effects due to the lack of affinity and selectivity. Therefore, there is an urgent need to design novel, potent, reversible and selective inhibitors for MAO-A/B. Selective inhibition of MAO-A results in the elevated level of serotonin and noradrenaline. Hence, MAO-A inhibitors can be used for improving the symptoms of depression. The selective MAO-B inhibitors are used with L-DOPA and/or dopamine agonists in the symptomatic treatment of Parkinson's disease. The present study was aimed to describe the recently developed hits of MAO inhibitors. At present, CADD techniques are gaining an attention in rationale drug discovery of MAO inhibitors, and several research groups employed CADD approaches on various chemical scaffolds to identify novel MAO inhibitors. These computational techniques assisted in the development of lead molecules with improved pharmacodynamics / pharmacokinetic properties toward MAOs. Further, CADD techniques provided a better understanding of structural aspects of molecular targets and lead molecules. The present review describes the importance of structural features of potential chemical scaffolds as well as the role of computational approaches like ligand docking, molecular dynamics, QSAR and pharmacophore modeling in the development of novel MAO inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. [Molecular genetic analysis and clinical aspects of patients with hereditary hemochromatosis].

    PubMed

    Lange, U; Teichmann, J; Dischereit, G

    2014-08-01

    The purpose of the study was to perform a molecular genetic analysis and to document clinical aspects in patients with hereditary hemochromatosis. The study included 33 outpatients (23 males average age 50.6 years and 10 females average age 60.6 years) with a disorder of iron metabolism (transferrin saturation > 75 %) as confirmation of hemochromatosis who were subjected to molecular genetic and clinical analyses. A homozygous mutation of the hemochromatosis (HFE) gene (C282YY) was detected in 63.6 %, a compound heterozygous mutation (C282Y/H63D) in 30.3% and no mutation of the HFE gene was detected in 6.1 %. The following organ manifestations could be objectified: arthralgia (78.8 %), liver disease (39.9 %), skin hyperpigmentation (30.3 %), osteoporosis (24.2 %), diabetes mellitus (24.2 %) and cardiomyopathy (12.1 %). Comparison between patients with heterozygous and homozygous hemochromatosis revealed the following differences: compound heterozygote patients presented less frequently with osteoarthritis of the metacarpophalangeal (MCP) joints and hands (85.7 %/71.4 % homozygotes vs. 60 %/60 % heterozygotes). Osteoarthritis of the shoulder joints and osteoporosis as well as hypothyroidism were more frequent in compound heterozygote patients, whereas osteoarthritis of the knee and hip joints as well as liver disease were more common in homozygote patients. No differences between both groups were seen with respect to the clinical manifestations of cardiomyopathy and diabetes mellitus. Prevalent causes of death in hereditary hemochromatosis are heart failure, liver disease (cirrhosis and hepatocellular carcinoma) and portal hypertension. Therefore, an early diagnosis, adequate therapy and genetic screening of family members are of great importance. Medicinal treatment will only effectively prevent deleterious organ involvement and subsequent complications if initiated at an early stage. Furthermore, an overview of the current data is given.

  6. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    PubMed

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

  7. Critical aspects of integrated monitoring systems for landslides risk management: strategies for a reliable approach

    NASA Astrophysics Data System (ADS)

    Castagnetti, C.; Bertacchini, E.; Capra, A.; Corsini, A.

    2012-04-01

    The use of advanced technologies for remotely monitor surface processes is a successful way for improving the knowledge of phenomena evolution. In addition, the integration of various techniques is becoming more and more common in order to implement early warning systems that can monitor the evolution of landslides in time and prevent emergencies. The reliability of those systems plays a key role when Public Administrations have to plan actions in case of disasters or for preventing an incoming emergency. To have confidence in the information given by the system is an essential condition for a successful policy aiming to protect the population. The research deals with the major critical aspects to be taken into account when implementing a reliable monitoring system for unstable slopes. The importance of those aspects is often neglected, unlike the effects of a not careful implementation and management of the system can lead to erroneous interpretations of the phenomenon itself. The case study which ruled the research and highlighted the actual need of guidelines for setting up a reliable monitoring system is the Valoria landslide, located in the Northern Italy. The system is based on the integration of an automatic Total Station (TS) measuring 45 reflectors and a master GPS, acting as the reference station for three rovers placed within the landslide. In order to monitor local disturbing effects, a bi-dimensional clinometer has been applied on the TS pillar. Topographic measurements have been also integrated with geotechnical sensors (inclinometers and piezometers) in a GIS for landslide risk management. At the very beginning, periodic measurements were carried out, while the system is now performing continuously since 2008. The system permitted to evaluate movements from few millimeter till some meters per day in most dangerous areas. A more spatially continuous description has been also provided by LiDAR and terrestrial SAR interferometry. Some of the most

  8. Clinical, Cellular, and Molecular Aspects in the Pathophysiology of Rosacea

    PubMed Central

    Steinhoff, Martin; Buddenkotte, Jörg; Aubert, Jerome; Sulk, Mathias; Novak, Pawel; Schwab, Verena D.; Mess, Christian; Cevikbas, Ferda; Rivier, Michel; Carlavan, Isabelle; Déret, Sophie; Rosignoli, Carine; Metze, Dieter; Luger, Thomas A.; Voegel, Johannes J.

    2013-01-01

    Rosacea is a chronic inflammatory skin disease of unknown etiology. Although described centuries ago, the pathophysiology of this disease is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been identified yet. Four subtypes and several variants of rosacea have been described. It is still unclear whether these subtypes represent a “developmental march” of different stages or are merely part of a syndrome that develops independently but overlaps clinically. Clinical and histopathological characteristics of rosacea make it a fascinating “human disease model” for learning about the connection between the cutaneous vascular, nervous, and immune systems. Innate immune mechanisms and dysregulation of the neurovascular system are involved in rosacea initiation and perpetuation, although the complex network of primary induction and secondary reaction of neuroimmune communication is still unclear. Later, rosacea may result in fibrotic facial changes, suggesting a strong connection between chronic inflammatory processes and skin fibrosis development. This review highlights recent molecular (gene array) and cellular findings and aims to integrate the different body defense mechanisms into a modern concept of rosacea pathophysiology. PMID:22076321

  9. Integrating molecular markers into the World Health Organization classification of CNS tumors: a survey of the neuro-oncology community.

    PubMed

    Aldape, Kenneth; Nejad, Romina; Louis, David N; Zadeh, Gelareh

    2017-03-01

    Molecular markers provide important biological and clinical information related to the classification of brain tumors, and the integration of relevant molecular parameters into brain tumor classification systems has been a widely discussed topic in neuro-oncology over the past decade. With recent advances in the development of clinically relevant molecular signatures and the 2016 World Health Organization (WHO) update, the views of the neuro-oncology community on such changes would be informative for implementing this process. A survey with 8 questions regarding molecular markers in tumor classification was sent to an email list of Society for Neuro-Oncology members and attendees of prior meetings (n=5065). There were 403 respondents. Analysis was performed using whole group response, based on self-reported subspecialty. The survey results show overall strong support for incorporating molecular knowledge into the classification and clinical management of brain tumors. Across all 7 subspecialty groups, ≥70% of respondents agreed to this integration. Interestingly, some variability is seen among subspecialties, notably with lowest support from neuropathologists, which may reflect their roles in implementing such diagnostic technologies. Based on a survey provided to the neuro-oncology community, we report strong support for the integration of molecular markers into the WHO classification of brain tumors, as well as for using an integrated "layered" diagnostic format. While membership from each specialty showed support, there was variation by specialty in enthusiasm regarding proposed changes. The initial results of this survey influenced the deliberations underlying the 2016 WHO classification of tumors of the central nervous system. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

  10. Apocalypse...now? Molecular epidemiology, predictive genetic tests, and social communication of genetic contents.

    PubMed

    Castiel, L D

    1999-01-01

    The author analyzes the underlying theoretical aspects in the construction of the molecular watershed of epidemiology and the concept of genetic risk, focusing on issues raised by contemporary reality: new technologies, globalization, proliferation of communications strategies, and the dilution of identity matrices. He discusses problems pertaining to the establishment of such new interdisciplinary fields as molecular epidemiology and molecular genetics. Finally, he analyzes the repercussions of the social communication of genetic content, especially as related to predictive genetic tests and cloning of animals, based on triumphal, deterministic metaphors sustaining beliefs relating to the existence and supremacy of concepts such as 'purity', 'essence', and 'unification' of rational, integrated 'I's/egos'.

  11. From classical to quantum and back: Hamiltonian adaptive resolution path integral, ring polymer, and centroid molecular dynamics

    NASA Astrophysics Data System (ADS)

    Kreis, Karsten; Kremer, Kurt; Potestio, Raffaello; Tuckerman, Mark E.

    2017-12-01

    Path integral-based methodologies play a crucial role for the investigation of nuclear quantum effects by means of computer simulations. However, these techniques are significantly more demanding than corresponding classical simulations. To reduce this numerical effort, we recently proposed a method, based on a rigorous Hamiltonian formulation, which restricts the quantum modeling to a small but relevant spatial region within a larger reservoir where particles are treated classically. In this work, we extend this idea and show how it can be implemented along with state-of-the-art path integral simulation techniques, including path-integral molecular dynamics, which allows for the calculation of quantum statistical properties, and ring-polymer and centroid molecular dynamics, which allow the calculation of approximate quantum dynamical properties. To this end, we derive a new integration algorithm that also makes use of multiple time-stepping. The scheme is validated via adaptive classical-path-integral simulations of liquid water. Potential applications of the proposed multiresolution method are diverse and include efficient quantum simulations of interfaces as well as complex biomolecular systems such as membranes and proteins.

  12. Brugada Syndrome. Clinical, Genetic, Molecular, Cellular and Ionic Aspects

    PubMed Central

    Antzelevitch, Charles; Patocskai, Bence

    2015-01-01

    The Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome first described as a new clinical entity in 1992. Electrocardiographically characterized by distinct coved type ST segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young adults, and less frequently in infants and children. The ECG manifestations of the BrS are often concealed and may be unmasked or aggravated by sodium channel blockers, a febrile state, vagotonic agents, as well as by tricyclic and tetracyclic antidepressants. An implantable cardioverter defibrillator (ICD) is the most widely accepted approach to therapy. Pharmacological therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an ICD is not possible. Isoproterenol, cilostazol and milrinone boost calcium channel current and drugs like quinidine, bepridil and the Chinese herb extract Wenxin Keli inhibit the transient outward current, acting to diminish the action potential (AP) notch and thus to suppress the substrate and trigger for VT/VF. Radiofrequency ablation of the right ventricular outflow tract epicardium of BrS patients has recently been shown to reduce arrhythmia-vulnerability and the ECG-manifestation of the disease, presumably by destroying the cells with more prominent AP notch. This review provides an overview of the clinical, genetic, molecular and cellular aspects of the BrS as well as the approach to therapy. PMID:26671757

  13. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: Multi-center molecular Ornstein-Zernike self-consistent field approach

    NASA Astrophysics Data System (ADS)

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-01

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl- + CH3Cl → ClCH3 + Cl-) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  14. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: multi-center molecular Ornstein-Zernike self-consistent field approach.

    PubMed

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-07

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl(-) + CH3Cl → ClCH3 + Cl(-)) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  15. Integrating open-source software applications to build molecular dynamics systems.

    PubMed

    Allen, Bruce M; Predecki, Paul K; Kumosa, Maciej

    2014-04-05

    Three open-source applications, NanoEngineer-1, packmol, and mis2lmp are integrated using an open-source file format to quickly create molecular dynamics (MD) cells for simulation. The three software applications collectively make up the open-source software (OSS) suite known as MD Studio (MDS). The software is validated through software engineering practices and is verified through simulation of the diglycidyl ether of bisphenol-a and isophorone diamine (DGEBA/IPD) system. Multiple simulations are run using the MDS software to create MD cells, and the data generated are used to calculate density, bulk modulus, and glass transition temperature of the DGEBA/IPD system. Simulation results compare well with published experimental and numerical results. The MDS software prototype confirms that OSS applications can be analyzed against real-world research requirements and integrated to create a new capability. Copyright © 2014 Wiley Periodicals, Inc.

  16. 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.

  17. Planetary Biology and Microbial Ecology: Molecular Ecology and the Global Nitrogen cycle

    NASA Technical Reports Server (NTRS)

    Nealson, Molly Stone (Editor); Nealson, Kenneth H. (Editor)

    1993-01-01

    This report summarizes the results of the Planetary Biology and Molecular Ecology's summer 1991 program, which was held at the Marine Biological Laboratory in Woods Hole, Massachusetts. The purpose of the interdisciplinary PBME program is to integrate, via lectures and laboratory work, the contributions of university and NASA scientists and student interns. The goals of the 1991 program were to examine several aspects of the biogeochemistry of the nitrogen cycle and to teach the application of modern methods of molecular genetics to field studies of organisms. Descriptions of the laboratory projects and protocols and abstracts and references of the lectures are presented.

  18. Molecular imaging probe development: a chemistry perspective

    PubMed Central

    Nolting, Donald D; Nickels, Michael L; Guo, Ning; Pham, Wellington

    2012-01-01

    Molecular imaging is an attractive modality that has been widely employed in many aspects of biomedical research; especially those aimed at the early detection of diseases such as cancer, inflammation and neurodegenerative disorders. The field emerged in response to a new research paradigm in healthcare that seeks to integrate detection capabilities for the prediction and prevention of diseases. This approach made a distinct impact in biomedical research as it enabled researchers to leverage the capabilities of molecular imaging probes to visualize a targeted molecular event non-invasively, repeatedly and continuously in a living system. In addition, since such probes are inherently compact, robust, and amenable to high-throughput production, these probes could potentially facilitate screening of preclinical drug discovery, therapeutic assessment and validation of disease biomarkers. They could also be useful in drug discovery and safety evaluations. In this review, major trends in the chemical synthesis and development of positron emission tomography (PET), optical and magnetic resonance imaging (MRI) probes are discussed. PMID:22943038

  19. Massively Parallel, Molecular Analysis Platform Developed Using a CMOS Integrated Circuit With Biological Nanopores

    PubMed Central

    Roever, Stefan

    2012-01-01

    A massively parallel, low cost molecular analysis platform will dramatically change the nature of protein, molecular and genomics research, DNA sequencing, and ultimately, molecular diagnostics. An integrated circuit (IC) with 264 sensors was fabricated using standard CMOS semiconductor processing technology. Each of these sensors is individually controlled with precision analog circuitry and is capable of single molecule measurements. Under electronic and software control, the IC was used to demonstrate the feasibility of creating and detecting lipid bilayers and biological nanopores using wild type α-hemolysin. The ability to dynamically create bilayers over each of the sensors will greatly accelerate pore development and pore mutation analysis. In addition, the noise performance of the IC was measured to be 30fA(rms). With this noise performance, single base detection of DNA was demonstrated using α-hemolysin. The data shows that a single molecule, electrical detection platform using biological nanopores can be operationalized and can ultimately scale to millions of sensors. Such a massively parallel platform will revolutionize molecular analysis and will completely change the field of molecular diagnostics in the future.

  20. Integrative taxonomy by molecular species delimitation: multi-locus data corroborate a new species of Balkan Drusinae micro-endemics.

    PubMed

    Vitecek, Simon; Kučinić, Mladen; Previšić, Ana; Živić, Ivana; Stojanović, Katarina; Keresztes, Lujza; Bálint, Miklós; Hoppeler, Felicitas; Waringer, Johann; Graf, Wolfram; Pauls, Steffen U

    2017-06-06

    Taxonomy offers precise species identification and delimitation and thus provides basic information for biological research, e.g. through assessment of species richness. The importance of molecular taxonomy, i.e., the identification and delimitation of taxa based on molecular markers, has increased in the past decade. Recently developed exploratory tools now allow estimating species-level diversity in multi-locus molecular datasets. Here we use molecular species delimitation tools that either quantify differences in intra- and interspecific variability of loci, or divergence times within and between species, or perform coalescent species tree inference to estimate species-level entities in molecular genetic datasets. We benchmark results from these methods against 14 morphologically readily differentiable species of a well-defined subgroup of the diverse Drusinae subfamily (Trichoptera, Limnephilidae). Using a 3798 bp (6 loci) molecular data set we aim to corroborate a geographically isolated new species by integrating comparative morphological studies and molecular taxonomy. Our results indicate that only multi-locus species delimitation provides taxonomically relevant information. The data further corroborate the new species Drusus zivici sp. nov. We provide differential diagnostic characters and describe the male, female and larva of this new species and discuss diversity patterns of Drusinae in the Balkans. We further discuss potential and significance of molecular species delimitation. Finally we argue that enhancing collaborative integrative taxonomy will accelerate assessment of global diversity and completion of reference libraries for applied fields, e.g., conservation and biomonitoring.

  1. Integrating Thermodynamic Models in Geodynamic Simulations: The Example of the Community Software ASPECT

    NASA Astrophysics Data System (ADS)

    Dannberg, J.; Heister, T.; Grove, R. R.; Gassmoeller, R.; Spiegelman, M. W.; Bangerth, W.

    2017-12-01

    Earth's surface shows many features whose genesis can only be understood through the interplay of geodynamic and thermodynamic models. This is particularly important in the context of melt generation and transport: Mantle convection determines the distribution of temperature and chemical composition, the melting process itself is then controlled by the thermodynamic relations and in turn influences the properties and the transport of melt. Here, we present our extension of the community geodynamics code ASPECT, which solves the equations of coupled magma/mantle dynamics, and allows to integrate different parametrizations of reactions and phase transitions: They may alternatively be implemented as simple analytical expressions, look-up tables, or computed by a thermodynamics software. As ASPECT uses a variety of numerical methods and solvers, this also gives us the opportunity to compare different approaches of modelling the melting process. In particular, we will elaborate on the spatial and temporal resolution that is required to accurately model phase transitions, and show the potential of adaptive mesh refinement when applied to melt generation and transport. We will assess the advantages and disadvantages of iterating between fluid dynamics and chemical reactions derived from thermodynamic models within each time step, or decoupling them, allowing for different time step sizes. Beyond that, we will expand on the functionality required for an interface between computational thermodynamics and fluid dynamics models from the geodynamics side. Finally, using a simple example of melting of a two-phase, two-component system, we compare different time-stepping and solver schemes in terms of accuracy and efficiency, in dependence of the time scales of fluid flow and chemical reactions relative to each other. Our software provides a framework to integrate thermodynamic models in high resolution, 3d simulations of coupled magma/mantle dynamics, and can be used as a tool

  2. Unravelling positive aspects of caregiving in dementia: An integrative review of research literature.

    PubMed

    Yu, Doris S F; Cheng, Sheung-Tak; Wang, Jungfang

    2018-03-01

    Family caregiving is the crucial informal care resource to lessen the burdens associated with dementia. Research in this field has focused on reducing the caregiver's burden, but little attention has been given to promoting the positive aspects of caregiving. To conduct a systematic critical review of research on the nature of positive aspects of caregiving, and the factors predicting this phenomenon among family caregivers of dementia patients, with the ultimate purpose of gaining insights to explain how and why it emerges. A systematic search of the literature was undertaken in the databases OvidMedline, CINAHL, PsycINFO, Web of Science and Scopus, using the keywords 'care* AND Alzheimer OR dementia AND 'positive aspect' OR 'positive experience' OR 'positive perceptions' OR reward OR gain OR 'satisfaction with care*' OR 'care* satisfaction' OR benefit OR uplift OR meaning OR enjoyment OR pleasure OR growth OR hope OR gratification. The Critical Appraisal Skills Programme checklists for qualitative and cohort studies were used to evaluate data quality. Narrative data synthesis was undertaken using the five-stage Whittermore and Knafl method. A total of 3862 articles were identified, of which 41 were included in this review. The key findings are that positive aspects of caregiving among family caregivers of dementia patients form a multi-dimensional construct which covers four key domains: a sense of personal accomplishment and gratification, feelings of mutuality in a dyadic relationship, an increase of family cohesion and functionality, and a sense of personal growth and purpose in life. By integrating the findings about the nature and conditions predicting positive aspects of caregiving, the presence of three conditions was identified as promoting the emergence of such qualities i) personal and social affirmation of role fulfilment, ii) effective cognitive emotional regulation and iii) contexts which favour finding meaning in the caregiving process. The findings

  3. Molecular anthropology in the genomic era.

    PubMed

    Destro-Bisol, Giovanni; Jobling, Mark A; Rocha, Jorge; Novembre, John; Richards, Martin B; Mulligan, Connie; Batini, Chiara; Manni, Franz

    2010-01-01

    Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have passed since the symposium "Classification and Human Evolution" (1962, Burg Wartenstein, Austria), where the term was formally introduced by Emil Zuckerkandl. In this time, Molecular Anthropology has developed both methodologically and theoretically and extended its applications, so covering key aspects of human evolution such as the reconstruction of the history of human populations and peopling processes, the characterization of DNA in extinct humans and the role of adaptive processes in shaping the genetic diversity of our species. In the current scientific panorama, molecular anthropologists have to face a double challenge. As members of the anthropological community, we are strongly committed to the integration of biological findings and other lines of evidence (e.g. linguistic and archaeological), while keeping in line with methodological innovations which are moving the approach from the genetic to the genomic level. In this framework, the meeting "DNA Polymorphisms in Human Populations: Molecular Anthropology in the Genomic Era" (Rome, December 3-5, 2009) offered an opportunity for discussion among scholars from different disciplines, while paying attention to the impact of recent methodological innovations. Here we present an overview of the meeting and discuss perspectives and prospects of Molecular Anthropology in the genomic era.

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

    PubMed

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

    2010-05-01

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

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

    PubMed Central

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

    2010-01-01

    Synthetic in vivo molecular ‘computers’ could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that ‘transduce’ mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi ‘computational’ module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting. PMID:20194121

  6. Detectable states, cycle fluxes, and motility scaling of molecular motor kinesin: An integrative kinetic graph theory analysis

    NASA Astrophysics Data System (ADS)

    Ren, Jie

    2017-12-01

    The process by which a kinesin motor couples its ATPase activity with concerted mechanical hand-over-hand steps is a foremost topic of molecular motor physics. Two major routes toward elucidating kinesin mechanisms are the motility performance characterization of velocity and run length, and single-molecular state detection experiments. However, these two sets of experimental approaches are largely uncoupled to date. Here, we introduce an integrative motility state analysis based on a theorized kinetic graph theory for kinesin, which, on one hand, is validated by a wealth of accumulated motility data, and, on the other hand, allows for rigorous quantification of state occurrences and chemomechanical cycling probabilities. An interesting linear scaling for kinesin motility performance across species is discussed as well. An integrative kinetic graph theory analysis provides a powerful tool to bridge motility and state characterization experiments, so as to forge a unified effort for the elucidation of the working mechanisms of molecular motors.

  7. Integration of Molecular Dynamics Based Predictions into the Optimization of De Novo Protein Designs: Limitations and Benefits.

    PubMed

    Carvalho, Henrique F; Barbosa, Arménio J M; Roque, Ana C A; Iranzo, Olga; Branco, Ricardo J F

    2017-01-01

    Recent advances in de novo protein design have gained considerable insight from the intrinsic dynamics of proteins, based on the integration of molecular dynamics simulations protocols on the state-of-the-art de novo protein design protocols used nowadays. With this protocol we illustrate how to set up and run a molecular dynamics simulation followed by a functional protein dynamics analysis. New users will be introduced to some useful open-source computational tools, including the GROMACS molecular dynamics simulation software package and ProDy for protein structural dynamics analysis.

  8. Molecular aspects of allergens in atopic dermatitis

    PubMed Central

    Campana, Raffaela; Dzoro, Sheron; Mittermann, Irene; Fedenko, Elena; Elisyutina, Olga; Khaitov, Musa; Karaulov, Alexander; Valenta, Rudolf

    2017-01-01

    Purpose of review Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis. Recent findings IgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE- and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach. Summary Molecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach. PMID:28622169

  9. Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

    PubMed Central

    Akhmanova, Maria; Osidak, Egor; Domogatsky, Sergey; Rodin, Sergey; Domogatskaya, Anna

    2015-01-01

    Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems. PMID:26351461

  10. Disease gene prioritization by integrating tissue-specific molecular networks using a robust multi-network model.

    PubMed

    Ni, Jingchao; Koyuturk, Mehmet; Tong, Hanghang; Haines, Jonathan; Xu, Rong; Zhang, Xiang

    2016-11-10

    Accurately prioritizing candidate disease genes is an important and challenging problem. Various network-based methods have been developed to predict potential disease genes by utilizing the disease similarity network and molecular networks such as protein interaction or gene co-expression networks. Although successful, a common limitation of the existing methods is that they assume all diseases share the same molecular network and a single generic molecular network is used to predict candidate genes for all diseases. However, different diseases tend to manifest in different tissues, and the molecular networks in different tissues are usually different. An ideal method should be able to incorporate tissue-specific molecular networks for different diseases. In this paper, we develop a robust and flexible method to integrate tissue-specific molecular networks for disease gene prioritization. Our method allows each disease to have its own tissue-specific network(s). We formulate the problem of candidate gene prioritization as an optimization problem based on network propagation. When there are multiple tissue-specific networks available for a disease, our method can automatically infer the relative importance of each tissue-specific network. Thus it is robust to the noisy and incomplete network data. To solve the optimization problem, we develop fast algorithms which have linear time complexities in the number of nodes in the molecular networks. We also provide rigorous theoretical foundations for our algorithms in terms of their optimality and convergence properties. Extensive experimental results show that our method can significantly improve the accuracy of candidate gene prioritization compared with the state-of-the-art methods. In our experiments, we compare our methods with 7 popular network-based disease gene prioritization algorithms on diseases from Online Mendelian Inheritance in Man (OMIM) database. The experimental results demonstrate that our methods

  11. Collective aspects of singlet fission in molecular crystals

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

    Teichen, Paul E.; Eaves, Joel D., E-mail: joel.eaves@colorado.edu

    2015-07-28

    We present a model to describe collective features of singlet fission in molecular crystals and analyze it using many-body theory. The model we develop allows excitonic states to delocalize over several chromophores which is consistent with the character of the excited states in many molecular crystals, such as the acenes, where singlet fission occurs. As singlet states become more delocalized and triplet states more localized, the rate of singlet fission increases. We also determine the conditions under which the two triplets resulting from fission are correlated. Using the Bethe Ansatz and an entanglement measure for indistinguishable bipartite systems, we calculatemore » the triplet-triplet entanglement as a function of the biexciton interaction strength. The biexciton interaction can produce bound biexciton states and provides a source of entanglement between the two triplets even when the triplets are spatially well separated. Significant entanglement between the triplet pair occurs well below the threshold for bound pair formation. Our results paint a dynamical picture that helps to explain why fission has been observed to be more efficient in molecular crystals than in their covalent dimer analogues and have consequences for photovoltaic efficiency models that assume that the two triplets can be extracted independently.« less

  12. Systemic lupus erythematosus: Clinical and experimental aspects

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

    Smolen, J.S.

    1987-01-01

    This text covers questions related to the history, etiology, pathogenesis, clinical aspects and therapy of systematic lupus erythematosus (SLE). Both animal models and human SLE are considered. With regard to basic science, concise information on cellular immunology, autoantibodies, viral aspects and molecular biology in SLE is provided. Clinical topics then deal with medical, dermatologic, neurologic, radiologic, pathologic, and therapeutic aspects. The book not only presents the most recent information on clinical and experimental insights, but also looks at future aspects related to the diagnosis and therapy of SLE.

  13. Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

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

    Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida; Fulp, William J.

    Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSImore » and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI

  14. Integrating anticipated nutrigenomics bioscience applications with ethical aspects.

    PubMed

    Lévesque, Lise; Ozdemir, Vural; Gremmen, Bart; Godard, Béatrice

    2008-03-01

    Nutrigenomics is a subspecialty of nutrition science which aims to understand how gene-diet interactions influence individuals' response to food, disease susceptibility, and population health. Yet ethical enquiry into this field is being outpaced by nutrigenomics bioscience. The ethical issues surrounding nutrigenomics face the challenges of a rapidly evolving field which bring forward the additional dimension of crossdisciplinary integrative research between social and biomedical sciences. This article outlines the emerging nutrigenomics definitions and concepts and analyzes the existing ethics literature concerning personalized nutrition and presents "points to consider" over ethical issues regarding future nutrigenomics applications. The interest in nutrigenomics coincides with a shift in emphasis in medicine and biosciences toward prevention of future disease susceptibilities rather than treatment of already established disease. Hence, unique ethical issues emerge concerning the extent to which nutrigenomics can alter our relation to food, boundaries between health and disease, and the folklore of medical practice. Nutrigenomics can result in new social values, norms, and responsibilities for both individuals and societies. Nutrigenomics is not only another new application of "-omics" technologies in the context of gene-diet interactions. Nutrigenomics may fundamentally change the way we perceive human illness while shifting the focus and broadening the scope of health interventions from patients to healthy individuals. In resource- and time-limited healthcare settings, this creates unique ethical dilemmas and distributive justice issues. Ethical aspects of nutrigenomics applications should be addressed proactively, as this new science develops and increasingly coalesces with other applications of genomics in medicine and public health.

  15. Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics.

    PubMed

    Penchovsky, Robert

    2012-10-19

    Here we describe molecular implementations of integrated digital circuits, including a three-input AND logic gate, a two-input multiplexer, and 1-to-2 decoder using allosteric ribozymes. Furthermore, we demonstrate a multiplexer-decoder circuit. The ribozymes are designed to seek-and-destroy specific RNAs with a certain length by a fully computerized procedure. The algorithm can accurately predict one base substitution that alters the ribozyme's logic function. The ability to sense the length of RNA molecules enables single ribozymes to be used as platforms for multiple interactions. These ribozymes can work as integrated circuits with the functionality of up to five logic gates. The ribozyme design is universal since the allosteric and substrate domains can be altered to sense different RNAs. In addition, the ribozymes can specifically cleave RNA molecules with triplet-repeat expansions observed in genetic disorders such as oculopharyngeal muscular dystrophy. Therefore, the designer ribozymes can be employed for scaling up computing and diagnostic networks in the fields of molecular computing and diagnostics and RNA synthetic biology.

  16. Some aspects of inventory integration

    Treesearch

    Jerry Leech

    2000-01-01

    Integrating such disparate topics as are covered by this conference is daunting, because to do it well requires in-depth expertise of many complex technical methodologies. Based on experiences in Asia and Australia, it is suggested that there can never be one inventory design or one planning system, it will increasingly be necessary to implement specialized inventories...

  17. Web-TCGA: an online platform for integrated analysis of molecular cancer data sets.

    PubMed

    Deng, Mario; Brägelmann, Johannes; Schultze, Joachim L; Perner, Sven

    2016-02-06

    The Cancer Genome Atlas (TCGA) is a pool of molecular data sets publicly accessible and freely available to cancer researchers anywhere around the world. However, wide spread use is limited since an advanced knowledge of statistics and statistical software is required. In order to improve accessibility we created Web-TCGA, a web based, freely accessible online tool, which can also be run in a private instance, for integrated analysis of molecular cancer data sets provided by TCGA. In contrast to already available tools, Web-TCGA utilizes different methods for analysis and visualization of TCGA data, allowing users to generate global molecular profiles across different cancer entities simultaneously. In addition to global molecular profiles, Web-TCGA offers highly detailed gene and tumor entity centric analysis by providing interactive tables and views. As a supplement to other already available tools, such as cBioPortal (Sci Signal 6:pl1, 2013, Cancer Discov 2:401-4, 2012), Web-TCGA is offering an analysis service, which does not require any installation or configuration, for molecular data sets available at the TCGA. Individual processing requests (queries) are generated by the user for mutation, methylation, expression and copy number variation (CNV) analyses. The user can focus analyses on results from single genes and cancer entities or perform a global analysis (multiple cancer entities and genes simultaneously).

  18. An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.

    PubMed

    Omer, Ankur; Singh, Poonam

    2017-05-01

    A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.

  19. Advanced Molecular Surveillance of Hepatitis C Virus

    PubMed Central

    Gonçalves Rossi, Livia Maria; Escobar-Gutierrez, Alejandro; Rahal, Paula

    2015-01-01

    Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted. PMID:25781918

  20. Integrable perturbed magnetic fields in toroidal geometry: An exact analytical flux surface label for large aspect ratio

    NASA Astrophysics Data System (ADS)

    Kallinikos, N.; Isliker, H.; Vlahos, L.; Meletlidou, E.

    2014-06-01

    An analytical description of magnetic islands is presented for the typical case of a single perturbation mode introduced to tokamak plasma equilibrium in the large aspect ratio approximation. Following the Hamiltonian structure directly in terms of toroidal coordinates, the well known integrability of this system is exploited, laying out a precise and practical way for determining the island topology features, as required in various applications, through an analytical and exact flux surface label.

  1. Integrable perturbed magnetic fields in toroidal geometry: An exact analytical flux surface label for large aspect ratio

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

    Kallinikos, N.; Isliker, H.; Vlahos, L.

    2014-06-15

    An analytical description of magnetic islands is presented for the typical case of a single perturbation mode introduced to tokamak plasma equilibrium in the large aspect ratio approximation. Following the Hamiltonian structure directly in terms of toroidal coordinates, the well known integrability of this system is exploited, laying out a precise and practical way for determining the island topology features, as required in various applications, through an analytical and exact flux surface label.

  2. Integration of Chinese medicine with Western medicine could lead to future medicine: molecular module medicine.

    PubMed

    Zhang, Chi; Zhang, Ge; Chen, Ke-ji; Lu, Ai-ping

    2016-04-01

    The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drug discovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.

  3. Towards aspect-oriented functional--structural plant modelling.

    PubMed

    Cieslak, Mikolaj; Seleznyova, Alla N; Prusinkiewicz, Przemyslaw; Hanan, Jim

    2011-10-01

    Functional-structural plant models (FSPMs) are used to integrate knowledge and test hypotheses of plant behaviour, and to aid in the development of decision support systems. A significant amount of effort is being put into providing a sound methodology for building them. Standard techniques, such as procedural or object-oriented programming, are not suited for clearly separating aspects of plant function that criss-cross between different components of plant structure, which makes it difficult to reuse and share their implementations. The aim of this paper is to present an aspect-oriented programming approach that helps to overcome this difficulty. The L-system-based plant modelling language L+C was used to develop an aspect-oriented approach to plant modelling based on multi-modules. Each element of the plant structure was represented by a sequence of L-system modules (rather than a single module), with each module representing an aspect of the element's function. Separate sets of productions were used for modelling each aspect, with context-sensitive rules facilitated by local lists of modules to consider/ignore. Aspect weaving or communication between aspects was made possible through the use of pseudo-L-systems, where the strict-predecessor of a production rule was specified as a multi-module. The new approach was used to integrate previously modelled aspects of carbon dynamics, apical dominance and biomechanics with a model of a developing kiwifruit shoot. These aspects were specified independently and their implementation was based on source code provided by the original authors without major changes. This new aspect-oriented approach to plant modelling is well suited for studying complex phenomena in plant science, because it can be used to integrate separate models of individual aspects of plant development and function, both previously constructed and new, into clearly organized, comprehensive FSPMs. In a future work, this approach could be further

  4. Towards aspect-oriented functional–structural plant modelling

    PubMed Central

    Cieslak, Mikolaj; Seleznyova, Alla N.; Prusinkiewicz, Przemyslaw; Hanan, Jim

    2011-01-01

    Background and Aims Functional–structural plant models (FSPMs) are used to integrate knowledge and test hypotheses of plant behaviour, and to aid in the development of decision support systems. A significant amount of effort is being put into providing a sound methodology for building them. Standard techniques, such as procedural or object-oriented programming, are not suited for clearly separating aspects of plant function that criss-cross between different components of plant structure, which makes it difficult to reuse and share their implementations. The aim of this paper is to present an aspect-oriented programming approach that helps to overcome this difficulty. Methods The L-system-based plant modelling language L+C was used to develop an aspect-oriented approach to plant modelling based on multi-modules. Each element of the plant structure was represented by a sequence of L-system modules (rather than a single module), with each module representing an aspect of the element's function. Separate sets of productions were used for modelling each aspect, with context-sensitive rules facilitated by local lists of modules to consider/ignore. Aspect weaving or communication between aspects was made possible through the use of pseudo-L-systems, where the strict-predecessor of a production rule was specified as a multi-module. Key Results The new approach was used to integrate previously modelled aspects of carbon dynamics, apical dominance and biomechanics with a model of a developing kiwifruit shoot. These aspects were specified independently and their implementation was based on source code provided by the original authors without major changes. Conclusions This new aspect-oriented approach to plant modelling is well suited for studying complex phenomena in plant science, because it can be used to integrate separate models of individual aspects of plant development and function, both previously constructed and new, into clearly organized, comprehensive FSPMs. In

  5. inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis

    PubMed Central

    2013-01-01

    Background Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. Results We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research

  6. inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis.

    PubMed

    Soares, Patrícia; Alves, Renato J; Abecasis, Ana B; Penha-Gonçalves, Carlos; Gomes, M Gabriela M; Pereira-Leal, José B

    2013-08-30

    Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research laboratories, hospitals or

  7. Review of Statistical Learning Methods in Integrated Omics Studies (An Integrated Information Science).

    PubMed

    Zeng, Irene Sui Lan; Lumley, Thomas

    2018-01-01

    Integrated omics is becoming a new channel for investigating the complex molecular system in modern biological science and sets a foundation for systematic learning for precision medicine. The statistical/machine learning methods that have emerged in the past decade for integrated omics are not only innovative but also multidisciplinary with integrated knowledge in biology, medicine, statistics, machine learning, and artificial intelligence. Here, we review the nontrivial classes of learning methods from the statistical aspects and streamline these learning methods within the statistical learning framework. The intriguing findings from the review are that the methods used are generalizable to other disciplines with complex systematic structure, and the integrated omics is part of an integrated information science which has collated and integrated different types of information for inferences and decision making. We review the statistical learning methods of exploratory and supervised learning from 42 publications. We also discuss the strengths and limitations of the extended principal component analysis, cluster analysis, network analysis, and regression methods. Statistical techniques such as penalization for sparsity induction when there are fewer observations than the number of features and using Bayesian approach when there are prior knowledge to be integrated are also included in the commentary. For the completeness of the review, a table of currently available software and packages from 23 publications for omics are summarized in the appendix.

  8. A minimally invasive blood-extraction system: elastic self-recovery actuator integrated with an ultrahigh- aspect-ratio microneedle.

    PubMed

    Li, Cheng Guo; Lee, Kwang; Lee, Chang Yeol; Dangol, Manita; Jung, Hyungil

    2012-08-28

    A minimally invasive blood-extraction system is fabricated by the integration of an elastic self-recovery actuator and an ultrahigh-aspect-ratio microneedle. The simple elastic self-recovery actuator converts finger force to elastic energy to provide power for blood extraction and transport without requiring an external source of power. This device has potential utility in the biomedical field within the framework of complete micro-electromechanical systems. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Spatiotemporal integration of molecular and anatomical data in virtual reality using semantic mapping.

    PubMed

    Soh, Jung; Turinsky, Andrei L; Trinh, Quang M; Chang, Jasmine; Sabhaney, Ajay; Dong, Xiaoli; Gordon, Paul Mk; Janzen, Ryan Pw; Hau, David; Xia, Jianguo; Wishart, David S; Sensen, Christoph W

    2009-01-01

    We have developed a computational framework for spatiotemporal integration of molecular and anatomical datasets in a virtual reality environment. Using two case studies involving gene expression data and pharmacokinetic data, respectively, we demonstrate how existing knowledge bases for molecular data can be semantically mapped onto a standardized anatomical context of human body. Our data mapping methodology uses ontological representations of heterogeneous biomedical datasets and an ontology reasoner to create complex semantic descriptions of biomedical processes. This framework provides a means to systematically combine an increasing amount of biomedical imaging and numerical data into spatiotemporally coherent graphical representations. Our work enables medical researchers with different expertise to simulate complex phenomena visually and to develop insights through the use of shared data, thus paving the way for pathological inference, developmental pattern discovery and biomedical hypothesis testing.

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

    PubMed

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

    2011-11-01

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

  11. [Ginseng prescription rules and molecular mechanism in treating coronary heart disease based on data mining and integrative pharmacology].

    PubMed

    Li, Sen; Tang, Shi-Huan; Liu, Jin-Ling; Su, Jin; He, Fu-Yuan

    2018-04-01

    The ancient dragon Materia Medica, Compendium of Materia Medica and other works recorded that the main effect of ginseng is tonifying qi. It is reported that the main active ingredient of ginseng is ginsenoside. Modern studies have found that ginseng mono saponins are effective for cardiovascular related diseases. This paper preliminary clarified the efficacy of traditional ginseng-nourishing qi and cardiovascular disease through the traditional Chinese medicine (TCM) inheritance auxiliary platform and integration platform of association of pharmacology. With the help of TCM inheritance auxiliary platform-analysis of "Chinese medicine database", Chinese medicine treatment of modern diseases that ginseng rules, so the traditional effect associated with modern medicine and pharmacology; application integration platform enrichment analysis on the target of drug and gene function, metabolic pathway, to further explore the molecular mechanism of ginseng in the treatment of coronary heart disease, aimed at mining the molecular mechanism of ginseng in the treatment of coronary heart disease. Chinese medicine containing ginseng 307 prescriptions, 87 kinds of disease indications, western medicine disease Chinese medicine therapy for ginseng main coronary heart disease; analysis of molecular mechanism of ginseng pharmacology integration platform for the treatment of coronary heart disease. Ginsenosides(Ra₁, Ra₂, Rb₁, Rb₂, Rg₁, Ro) bind these targets, PRKAA1, PRKAA2, NDUFA4, COX5B, UQCRC1, affect chemokines, non-alcoholic fatty liver, gonadotropin, carbon metabolism, glucose metabolism and other pathways to treat coronary heart disease indirectly. The molecular mechanism of Panax ginseng's multi-component, multi-target and synergistic action is preliminarily elucidated in this paper. Copyright© by the Chinese Pharmaceutical Association.

  12. A symplectic integration method for elastic filaments

    NASA Astrophysics Data System (ADS)

    Ladd, Tony; Misra, Gaurav

    2009-03-01

    Elastic rods are a ubiquitous coarse-grained model of semi-flexible biopolymers such as DNA, actin, and microtubules. The Worm-Like Chain (WLC) is the standard numerical model for semi-flexible polymers, but it is only a linearized approximation to the dynamics of an elastic rod, valid for small deflections; typically the torsional motion is neglected as well. In the standard finite-difference and finite-element formulations of an elastic rod, the continuum equations of motion are discretized in space and time, but it is then difficult to ensure that the Hamiltonian structure of the exact equations is preserved. Here we discretize the Hamiltonian itself, expressed as a line integral over the contour of the filament. This discrete representation of the continuum filament can then be integrated by one of the explicit symplectic integrators frequently used in molecular dynamics. The model systematically approximates the continuum partial differential equations, but has the same level of computational complexity as molecular dynamics and is constraint free. Numerical tests show that the algorithm is much more stable than a finite-difference formulation and can be used for high aspect ratio filaments, such as actin. We present numerical results for the deterministic and stochastic motion of single filaments.

  13. Arsenic Uptake, Toxicity, Detoxification, and Speciation in Plants: Physiological, Biochemical, and Molecular Aspects

    PubMed Central

    Abbas, Ghulam; Murtaza, Behzad; Bibi, Irshad; Shahid, Muhammad; Khan, Muhammad Imran; Amjad, Muhammad; Hussain, Munawar; Natasha

    2018-01-01

    Environmental contamination with arsenic (As) is a global environmental, agricultural and health issue due to the highly toxic and carcinogenic nature of As. Exposure of plants to As, even at very low concentration, can cause many morphological, physiological, and biochemical changes. The recent research on As in the soil-plant system indicates that As toxicity to plants varies with its speciation in plants (e.g., arsenite, As(III); arsenate, As(V)), with the type of plant species, and with other soil factors controlling As accumulation in plants. Various plant species have different mechanisms of As(III) or As(V) uptake, toxicity, and detoxification. This review briefly describes the sources and global extent of As contamination and As speciation in soil. We discuss different mechanisms responsible for As(III) and As(V) uptake, toxicity, and detoxification in plants, at physiological, biochemical, and molecular levels. This review highlights the importance of the As-induced generation of reactive oxygen species (ROS), as well as their damaging impacts on plants at biochemical, genetic, and molecular levels. The role of different enzymatic (superoxide dismutase, catalase, glutathione reductase, and ascorbate peroxidase) and non-enzymatic (salicylic acid, proline, phytochelatins, glutathione, nitric oxide, and phosphorous) substances under As(III/V) stress have been delineated via conceptual models showing As translocation and toxicity pathways in plant species. Significantly, this review addresses the current, albeit partially understood, emerging aspects on (i) As-induced physiological, biochemical, and genotoxic mechanisms and responses in plants and (ii) the roles of different molecules in modulation of As-induced toxicities in plants. We also provide insight on some important research gaps that need to be filled to advance our scientific understanding in this area of research on As in soil-plant systems. PMID:29301332

  14. Triple-aspect monism: physiological, mental unconscious and conscious aspects of brain activity.

    PubMed

    Pereira, Alfredo

    2014-06-01

    Brain activity contains three fundamental aspects: (a) The physiological aspect, covering all kinds of processes that involve matter and/or energy; (b) the mental unconscious aspect, consisting of dynamical patterns (i.e., frequency, amplitude and phase-modulated waves) embodied in neural activity. These patterns are variously operated (transmitted, stored, combined, matched, amplified, erased, etc), forming cognitive and emotional unconscious processes and (c) the mental conscious aspect, consisting of feelings experienced in the first-person perspective and cognitive functions grounded in feelings, as memory formation, selection of the focus of attention, voluntary behavior, aesthetical appraisal and ethical judgment. Triple-aspect monism (TAM) is a philosophical theory that provides a model of the relation of the three aspects. Spatially distributed neuronal dendritic potentials generate amplitude-modulated waveforms transmitted to the extracellular medium and adjacent astrocytes, prompting the formation of large waves in the astrocyte network, which are claimed to both integrate distributed information and instantiate feelings. According to the valence of the feeling, the large wave feeds back on neuronal synapses, modulating (reinforcing or depressing) cognitive and behavioral functions.

  15. The eukaryotic cell originated in the integration and redistribution of hyperstructures from communities of prokaryotic cells based on molecular complementarity.

    PubMed

    Norris, Vic; Root-Bernstein, Robert

    2009-06-04

    In the "ecosystems-first" approach to the origins of life, networks of non-covalent assemblies of molecules (composomes), rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the origin of eukaryotic cells through the integration of mixed populations of bacteria. We suggest that mutualism and symbiosis resulted in cellular mergers entailing the loss of redundant hyperstructures, the uncoupling of transcription and translation, and the emergence of introns and multiple chromosomes. Molecular complementarity also facilitated integration of bacterial hyperstructures to perform cytoskeletal and movement functions.

  16. Evaluation of Kirkwood-Buff integrals via finite size scaling: a large scale molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Dednam, W.; Botha, A. E.

    2015-01-01

    Solvation of bio-molecules in water is severely affected by the presence of co-solvent within the hydration shell of the solute structure. Furthermore, since solute molecules can range from small molecules, such as methane, to very large protein structures, it is imperative to understand the detailed structure-function relationship on the microscopic level. For example, it is useful know the conformational transitions that occur in protein structures. Although such an understanding can be obtained through large-scale molecular dynamic simulations, it is often the case that such simulations would require excessively large simulation times. In this context, Kirkwood-Buff theory, which connects the microscopic pair-wise molecular distributions to global thermodynamic properties, together with the recently developed technique, called finite size scaling, may provide a better method to reduce system sizes, and hence also the computational times. In this paper, we present molecular dynamics trial simulations of biologically relevant low-concentration solvents, solvated by aqueous co-solvent solutions. In particular we compare two different methods of calculating the relevant Kirkwood-Buff integrals. The first (traditional) method computes running integrals over the radial distribution functions, which must be obtained from large system-size NVT or NpT simulations. The second, newer method, employs finite size scaling to obtain the Kirkwood-Buff integrals directly by counting the particle number fluctuations in small, open sub-volumes embedded within a larger reservoir that can be well approximated by a much smaller simulation cell. In agreement with previous studies, which made a similar comparison for aqueous co-solvent solutions, without the additional solvent, we conclude that the finite size scaling method is also applicable to the present case, since it can produce computationally more efficient results which are equivalent to the more costly radial distribution

  17. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

    PubMed

    Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

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

    PubMed

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

    2017-04-01

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

  19. Coherence and congruence: two aspects of personality integration.

    PubMed

    Sheldon, K M; Kasser, T

    1995-03-01

    Coherence and congruence-based measures of personality integration were related to a variety of healthy personality characteristics. Functional coherence was defined as occurring when participants' "personal strivings" (R.A. Emmons, 1986) help bring about each other or help bring about higher level goals. Organismic congruence was defined as occurring when participants strive for self-determined reasons or when strivings help bring about intrinsic rather than extrinsic higher level goals. Study 1 found the integration measures were related to each other and to inventory measures of health and well-being. Study 2 showed that these goal integration measures were also related to role system integration and were prospective predictors of daily mood, vitality, and engagement in meaningful as opposed to distracting activities.

  20. New methods for accelerating the convergence of molecular electronic integrals over exponential type orbitals

    NASA Astrophysics Data System (ADS)

    Safouhi, Hassan; Hoggan, Philip

    2003-01-01

    This review on molecular integrals for large electronic systems (MILES) places the problem of analytical integration over exponential-type orbitals (ETOs) in a historical context. After reference to the pioneering work, particularly by Barnett, Shavitt and Yoshimine, it focuses on recent progress towards rapid and accurate analytic solutions of MILES over ETOs. Software such as the hydrogenlike wavefunction package Alchemy by Yoshimine and collaborators is described. The review focuses on convergence acceleration of these highly oscillatory integrals and in particular it highlights suitable nonlinear transformations. Work by Levin and Sidi is described and applied to MILES. A step by step description of progress in the use of nonlinear transformation methods to obtain efficient codes is provided. The recent approach developed by Safouhi is also presented. The current state of the art in this field is summarized to show that ab initio analytical work over ETOs is now a viable option.

  1. [Stress and the molecular basis of psychosomatics].

    PubMed

    Peters, E M J

    2013-06-01

    Stress and skin-an inseparable pair, this is how many of our patients perceive it and even clinicians are willing to integrate psychosomatic aspects into their recommendations if nothing from the somatic repertoire provides sufficient treatment. How the stress reaches the skin however is still an enigmatic matter to most lay people and professionals alike. Interestingly, psychoneuroimmunological research since the 1970s has produced a flood of valuable data. We now know that stressors, be it biochemical or psychoemotional, always elicit a neuroendocrine stress reaction with consequences for the immune response and therefore especially chronic inflammatory skin diseases. Here we employ allergic inflammation/atopic dermatitis and psoriasis as instructive model diseases to discuss basic mechanisms of molecular psychosomatic effects on chronic inflammation. The aim is to enhance pathogenetic understanding and open the door for the development and employment of integrated therapeutic concepts in dermatology.

  2. [CONTEMPORARY MOLECULAR-GENETIC METHODS USED FOR ETIOLOGIC DIAGNOSTICS OF SEPSIS].

    PubMed

    Gavrilov, S N; Skachkova, T S; Shipulina, O Yu; Savochkina, Yu A; Shipulin, G A; Maleev, V V

    2016-01-01

    Etiologic diagnostics of sepsis is one of the most difficult problems of contemporary medicine due to a wide variety of sepsis causative agents, many of which are components of normal human microflora. Disadvantages of contemporary "golden standard" of microbiologic diagnostics of sepsis etiology by seeding of blood for sterility are duration of cultivation, limitation in detection of non-cultivable forms of microorganisms, significant effect of preliminary empiric antibiotics therapy on results of the analysis. Methods of molecular diagnostics that are being actively developed and integrated during the last decade are deprived of these disadvantages. Main contemporary methods of molecular-biological diagnostics are examined in the review, actualdata on their diagnostic characteristic are provided. Special attention is given to methods of PCR-diagnostics, including novel Russian developments. Methods of nucleic acid hybridization and proteomic analysis are examined in comparative aspect. Evaluation of application and perspectives of development of methods of molecular diagnostics of sepsis is given.

  3. Integrating multiple disturbance aspects: management of an invasive thistle, Carduus nutans.

    PubMed

    Zhang, Rui; Shea, Katriona

    2012-11-01

    Disturbances occur in most ecological systems, and play an important role in biological invasions. We delimit five key disturbance aspects: intensity, frequency, timing, duration and extent. Few studies address more than one of these aspects, yet interactions and interdependence between aspects may lead to complex outcomes. In a two-cohort experimental study, we examined how multiple aspects (intensity, frequency and timing) of a mowing disturbance regime affect the survival, phenology, growth and reproduction of an invasive thistle Carduus nutans (musk thistle). Our results show that high intensity and late timing strongly delay flowering phenology and reduce plant survival, capitulum production and plant height. A significant interaction between intensity and timing further magnifies the main effects. Unexpectedly, high frequency alone did not effectively reduce reproduction. However, a study examining only frequency and intensity, and not timing, would have erroneously attributed the importance of timing to frequency. We used management of an invasive species as an example to demonstrate the importance of a multiple-aspect disturbance framework. Failure to consider possible interactions, and the inherent interdependence of certain aspects, could result in misinterpretation and inappropriate management efforts. This framework can be broadly applied to improve our understanding of disturbance effects on individual responses, population dynamics and community composition.

  4. Integrating content and structure aspects of the self: traits, values, and self-improvement.

    PubMed

    Roccas, Sonia; Sagiv, Lilach; Oppenheim, Shani; Elster, Andrey; Gal, Avigail

    2014-04-01

    Research on the structure of the self has mostly developed separately from research on its content. Taking an integrative approach, we studied two structural aspects of the self associated with self-improvement--self-discrepancies and perceived mutability--by focusing on two content areas, traits and values. In Studies 1A-C, 337 students (61% female) reported self-discrepancies in values and traits, with the finding that self-discrepancies in values are smaller than in traits. In Study 2 (80 students, 41% female), we experimentally induced either high or low mutability and measured perceived mutability of traits and values. We found that values are perceived as less mutable than traits. In Study 3, 99 high school students (60% female) reported their values, traits, and the extent to which they wish to change them. We found that values predict the wish to change traits, whereas traits do not predict the wish to change values. In Study 4, 172 students (47.7% female) were assigned to one of four experimental conditions in which they received feedback denoting either uniqueness or similarity to others, on either their values or their traits. The results indicated that feedback that one's values (but not traits) are unique affected self-esteem. Integrating between theories of content and structure of the self can contribute to the development of both. © 2013 Wiley Periodicals, Inc.

  5. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

    PubMed

    Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

    2018-01-01

    Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

  6. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

    PubMed Central

    Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

    2018-01-01

    Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

  7. Molecularly Imprinted Polymers: Present and Future Prospective

    PubMed Central

    Vasapollo, Giuseppe; Sole, Roberta Del; Mergola, Lucia; Lazzoi, Maria Rosaria; Scardino, Anna; Scorrano, Sonia; Mele, Giuseppe

    2011-01-01

    Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented. PMID:22016636

  8. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

    PubMed

    Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

    2013-04-01

    Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator

  9. Integrating Art.

    ERIC Educational Resources Information Center

    BCATA Journal for Art Teachers, 1991

    1991-01-01

    These articles focus on art as a component of interdisciplinary integration. (1) "Integrated Curriculum and the Visual Arts" (Anna Kindler) considers various aspects of integration and implications for art education. (2) "Integration: The New Literacy" (Tim Varro) illustrates how the use of technology can facilitate…

  10. Mass spectrometric characterization of membrane integral low molecular weight proteins from photosystem II in barley etioplasts.

    PubMed

    Plöscher, Matthias; Granvogl, Bernhard; Zoryan, Mikael; Reisinger, Veronika; Eichacker, Lutz Andreas

    2009-02-01

    In Photosystem II (PSII), a high number of plastid encoded and membrane integral low molecular weight proteins smaller than 10 kDa, the proteins PsbE, F, H, I, J, K, L, M, N, Tc, Z and the nuclear encoded PsbW, X, Y1, Y2 proteins have been described. Here we show that all low molecular weight proteins of PSII already accumulate in the etioplast membrane fraction in darkness, whereas PsaI and PsaJ of photosystem I (PSI) represent the only low molecular weight proteins that do not accumulate in darkness. We found by BN-PAGE separation of membrane protein complexes and selective MS that the accumulation of one-helix proteins from PSII is light independent and occurs in etioplasts. In contrast, in chloroplasts isolated from light-grown plants, low molecular weight proteins were found to specifically accumulate in PSI and II complexes. Our results demonstrate how plants grown in darkness prepare for the induction of chlorophyll dependent photosystem assembly upon light perception. We anticipate that our investigation will provide the essential means for the analysis of protein assembly in any membrane utilizing low molecular weight protein subunits.

  11. Model for integrated management of quality, labor risks prevention, environment and ethical aspects, applied to R&D&I and production processes in an organization

    NASA Astrophysics Data System (ADS)

    González, M. R.; Torres, F.; Yoldi, V.; Arcega, F.; Plaza, I.

    2012-04-01

    It is proposed an integrated management model for an organization. This model is based on the continuous improvement Plan-Do-Check-Act cycle and it intends to integrate the environmental, risk prevention and ethical aspects as well as research, development and innovation projects management in the general quality management structure proposed by ISO 9001:2008. It aims to fulfill the standards ISO 9001, ISO 14001, OSHAS 18001, SGE 21 y 166002.

  12. Aspects of Piaget's cognitive developmental psychology and neurobiology of psychotic disorders - an integrative model.

    PubMed

    Gebhardt, Stefan; Grant, Phillip; von Georgi, Richard; Huber, Martin T

    2008-09-01

    Psychological, neurobiological and neurodevelopmental approaches have frequently been used to provide pathogenic concepts on psychotic disorders. However, aspects of cognitive developmental psychology have hardly been considered in current models. Using a hypothesis-generating approach an integration of these concepts was conducted. According to Piaget (1896-1980), assimilation and accommodation as forms of maintenance and modification of cognitive schemata represent fundamental processes of the brain. In general, based on the perceived input stimuli, cognitive schemata are developed resulting in a conception of the world, the realistic validity and the actuality of which is still being controlled and modified by cognitive adjustment processes. In psychotic disorders, however, a disproportion of environmental demands and the ability to activate required neuronal adaptation processes occurs. We therefore hypothesize a failure of the adjustment of real and requested output patterns. As a consequence autonomous cognitive schemata are generated, which fail to adjust with reality resulting in psychotic symptomatology. Neurobiological, especially neuromodulatory and neuroplastic processes play a central role in these perceptive and cognitive processes. In conclusion, integration of cognitive developmental psychology into the existing pathogenic concepts of psychotic disorders leads to interesting insights into basic disease mechanisms and also guides future research in the cognitive neuroscience of such disorders.

  13. Echinococcus oligarthrus in the subtropical region of Argentina: First integration of morphological and molecular analyses determines two distinct populations.

    PubMed

    Arrabal, Juan Pablo; Avila, Hector Gabriel; Rivero, Maria Romina; Camicia, Federico; Salas, Martin Miguel; Costa, Sebastián A; Nocera, Carlos G; Rosenzvit, Mara C; Kamenetzky, Laura

    2017-06-15

    Echinococcosis is a parasitic zoonosis that is considered as a neglected disease by the World Health Organization. The species Echinococcus oligarthrus is one of the causative agents of Neotropical echinococcosis, which is a poorly understood disease that requires a complex medical examination, may threaten human life, and is frequently associated with a low socioeconomic status. Morphological and genetic diversity in E. oligarthrus remains unknown. The aim of this work is to identify and characterize E. oligarthrus infections in sylvatic animals from the Upper Paraná Atlantic Forest in the province of Misiones, Argentina, by following an integrative approach that links morphological, genetic and ecological aspects. This study demonstrates, for the first time, one of the complete life cycles of E. oligarthrus in an important ecoregion. The Upper Paraná Atlantic Forest constitutes the largest remnant continuous forest of the Atlantic Forest, representing 7% of the world's biodiversity. This is the first molecular determination of E. oligarthrus in Argentina. In addition, the agouti (Dasyprocta azarae), the ocelot (Leopardus pardalis) and the puma (Puma concolor) were identified as sylvatic hosts of Neotropical echinococcosis caused by E. oligarthrus. Mitochondrial and nuclear molecular marker analyses showed a high genetic diversity in E. oligarthrus. Moreover, the genetic distance found among E. oligarthrus isolates is higher than the one observed among Echinococcus granulosus genotypes, which clearly indicates that there are at least two different E. oligarthrus populations in Argentina. This study provides valuable information to understand the underlying conditions that favour the maintenance of E. oligarthrus in sylvatic cycles and to evaluate its zoonotic significance for devising preventive measures for human and animal wellbeing. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. New aspects of π–d interactions in magnetic molecular conductors

    PubMed Central

    Sugimoto, Toyonari; Fujiwara, Hideki; Noguchi, Satoru; Murata, Keizo

    2009-01-01

    The 2 : 1 cation radical salts of bent donor molecules of ethylenedithio-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDT-TTFVO), ethylenedithio-diselenadithiafulvalenoquinone-1,3-dithiolemethide (EDT-DSDTFVO), ethylenedithio-diselenadithiafulvalenothioquinone-1,3-diselenolemethide (EDT-DSDTFVSDS), ethylenedioxy-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDO-TTFVO) and ethylenedioxy-tetrathiafulvalenoquinone-1,3-diselenolemethide (EDO-TTFVODS) with FeX4− (X = Cl, Br) ions are prepared by electrocrystallization. The crystal structures of these salts are composed of alternately stacked donor molecule and magnetic anion layers. The band structures of the donor molecule layers are calculated using the overlap integrals between neighboring donor molecules and are compared with the observed electronic transport properties. The magnetic ordering of the Fe(III) d spins of FeX4− ions is determined from magnetization and heat capacity measurements. The magnetic ordering temperatures are estimated by considering a combination of a direct d–d interaction between the d spins and an indirect π–d interaction between the conduction π electron and the d spins, whose magnitudes are separately calculated from the crystal structures with an extended Hückel molecular orbital method. The occurrence of a π–d interaction is proved by the negative magnetoresistance, and the magnitude of magnetoresistance reflects the strength of the π–d interaction. The effect of pressure on the magnetoresistance is studied, and the result indicates that the magnitude of magnetoresistance increases, namely, the π–d interaction is enhanced with increasing pressure. From these experimental results it is shown that (EDT-TTFVO)2•FeBr4 is a ferromagnetic semiconductor, (EDT-DSDTFVO)2•FeX4 (X = Cl, Br) and (EDT-DSDTFVSDS)2•FeBr4 are metals exhibiting antiferromagnetic ordering of the d spins, and (EDO-TTFVO)2•FeCl4 and (EDO-TTFVODS)2•FeBr4•(DCE)0.5 (DCE =-dichloroethane) are

  15. Integrated software environment based on COMKAT for analyzing tracer pharmacokinetics with molecular imaging.

    PubMed

    Fang, Yu-Hua Dean; Asthana, Pravesh; Salinas, Cristian; Huang, Hsuan-Ming; Muzic, Raymond F

    2010-01-01

    An integrated software package, Compartment Model Kinetic Analysis Tool (COMKAT), is presented in this report. COMKAT is an open-source software package with many functions for incorporating pharmacokinetic analysis in molecular imaging research and has both command-line and graphical user interfaces. With COMKAT, users may load and display images, draw regions of interest, load input functions, select kinetic models from a predefined list, or create a novel model and perform parameter estimation, all without having to write any computer code. For image analysis, COMKAT image tool supports multiple image file formats, including the Digital Imaging and Communications in Medicine (DICOM) standard. Image contrast, zoom, reslicing, display color table, and frame summation can be adjusted in COMKAT image tool. It also displays and automatically registers images from 2 modalities. Parametric imaging capability is provided and can be combined with the distributed computing support to enhance computation speeds. For users without MATLAB licenses, a compiled, executable version of COMKAT is available, although it currently has only a subset of the full COMKAT capability. Both the compiled and the noncompiled versions of COMKAT are free for academic research use. Extensive documentation, examples, and COMKAT itself are available on its wiki-based Web site, http://comkat.case.edu. Users are encouraged to contribute, sharing their experience, examples, and extensions of COMKAT. With integrated functionality specifically designed for imaging and kinetic modeling analysis, COMKAT can be used as a software environment for molecular imaging and pharmacokinetic analysis.

  16. Genetics, Molecular, and Proteomics Advances in Filamentous Fungi.

    PubMed

    Sharma Ghimire, Prakriti; Jin, Cheng

    2017-10-01

    Filamentous fungi play a dynamic role in health and the environment. In addition, their unique and complex hyphal structures are involved in their morphogenesis, integrity, synthesis, and degradation, according to environmental and physiological conditions and resource availability. However, in biotechnology, it has a great value in the production of enzymes, pharmaceuticals, and food ingredients. The beginning of nomenclature of overall fungi started in early 1990 after which the categorization, interior and exterior mechanism, function, molecular and genetics study took pace. This mini-review has emphasized some of the important aspects of filamentous fungi, their pattern of life cycle, history, and development of different strategic methods applied to exploit this unique organism. New trends and concepts that have been applied to overcome obstacle because of their basic structure related to genomics and systems biology has been presented. Furthermore, the future aspects and challenges that need to be deciphered to get a bigger and better picture of filamentous fungi have been discussed.

  17. Spiers Memorial Lecture. Molecular mechanics and molecular electronics.

    PubMed

    Beckman, Robert; Beverly, Kris; Boukai, Akram; Bunimovich, Yuri; Choi, Jang Wook; DeIonno, Erica; Green, Johnny; Johnston-Halperin, Ezekiel; Luo, Yi; Sheriff, Bonnie; Stoddart, Fraser; Heath, James R

    2006-01-01

    We describe our research into building integrated molecular electronics circuitry for a diverse set of functions, and with a focus on the fundamental scientific issues that surround this project. In particular, we discuss experiments aimed at understanding the function of bistable rotaxane molecular electronic switches by correlating the switching kinetics and ground state thermodynamic properties of those switches in various environments, ranging from the solution phase to a Langmuir monolayer of the switching molecules sandwiched between two electrodes. We discuss various devices, low bit-density memory circuits, and ultra-high density memory circuits that utilize the electrochemical switching characteristics of these molecules in conjunction with novel patterning methods. We also discuss interconnect schemes that are capable of bridging the micrometre to submicrometre length scales of conventional patterning approaches to the near-molecular length scales of the ultra-dense memory circuits. Finally, we discuss some of the challenges associated with fabricated ultra-dense molecular electronic integrated circuits.

  18. Mid-infrared integrated optics: versatile hot embossing of mid-infrared glasses for on-chip planar waveguides for molecular sensing

    NASA Astrophysics Data System (ADS)

    Seddon, Angela B.; Abdel-Moneim, Nabil S.; Zhang, Lian; Pan, Wei J.; Furniss, David; Mellor, Christopher J.; Kohoutek, Tomas; Orava, Jiri; Wagner, Tomas; Benson, Trevor M.

    2014-07-01

    The versatility of hot embossing for shaping photonic components on-chip for mid-infrared (IR) integrated optics, using a hard mold, is demonstrated. Hot embossing via fiber-on-glass (FOG), thermally evaporated films, and radio frequency (RF)-sputtered films on glass are described. Mixed approaches of combined plasma etching and hot embossing increase the versatility still further for engineering optical circuits on a single platform. Application of these methodologies for fabricating molecular-sensing devices on-chip is discussed with a view to biomedical sensing. Future prospects for using photonic integration for the new field of mid-IR molecular sensing are appraised. Also, common methods of measuring waveguide optical loss are critically compared, regarding their susceptibility to artifacts which tend artificially to depress, or enhance, the waveguide optical loss.

  19. Molecular Pathological Epidemiology of Epigenetics: Emerging Integrative Science to Analyze Environment, Host, and Disease

    PubMed Central

    Ogino, Shuji; Lochhead, Paul; Chan, Andrew T.; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M.; Meyerhardt, Jeffrey A.; Meissner, Alexander; Schernhammer, Eva S.; Fuchs, Charles S.; Giovannucci, Edward

    2013-01-01

    Epigenetics acts as an interface between environmental / exogenous factors, cellular responses and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases, including non-neoplastic disorders (e.g., cardiovascular diseases, hypertension, diabetes mellitus, autoimmune diseases, and some infectious diseases) and neoplasms (e.g., leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc.) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. DNA methylation assays are widely applied to formalin-fixed paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiologic factors, cellular molecular characteristics, and disease evolution, the field of “Molecular Pathological Epidemiology (MPE)” has emerged as an interdisciplinary integration of “molecular pathology” and “epidemiology”, with a similar conceptual framework to systems biology and network medicine. In contrast to traditional epidemiologic research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle; that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macro-environment and tissue microenvironment. The widespread application of epigenomics (e.g., methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator phenotype, LINE-1 hypomethylation, etc.), and host-disease interactions. MPE may represent a logical evolution of GWAS, termed “GWAS-MPE approach”. Though epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell

  20. Molecular approaches to epidemiology and clinical aspects of malaria.

    PubMed

    Brown, G V; Beck, H P; Molyneux, M; Marsh, K

    2000-10-01

    Malaria is a problem of global importance, responsible for 1-2 million deaths per year, mainly in African children, as well as considerable morbidity manifested as severe anaemia and encephalopathy in young children. Fundamental to the development of new tools for malaria control in humans is an increased understanding of key features of malaria infection, such as the diversity of outcome in different individuals, the understanding of different manifestations of the disease and of the mechanisms of immunity that allow clinical protection in the face of ongoing low-grade infection (concomitant immunity or premunition). Here, Graham Brown and colleagues review some of the ways in which molecular approaches might be used to increase our understanding of the epidemiology and clinical manifestations of malaria, as discussed at the Molecular Approaches to Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.

  1. Molecular implementation of molecular shift register memories

    NASA Technical Reports Server (NTRS)

    Beratan, David N. (Inventor); Onuchic, Jose N. (Inventor)

    1991-01-01

    An electronic shift register memory (20) at the molecular level is described. The memory elements are based on a chain of electron transfer molecules (22) and the information is shifted by photoinduced (26) electron transfer reactions. Thus, multi-step sequences of charge transfer reactions are used to move charge with high efficiency down a molecular chain. The device integrates compositions of the invention onto a VLSI substrate (36), providing an example of a molecular electronic device which may be fabricated. Three energy level schemes, molecular implementation of these schemes, optical excitation strategies, charge amplification strategies, and error correction strategies are described.

  2. [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.

  3. TOPICAL REVIEW: New aspects of π-d interactions in magnetic molecular conductors

    NASA Astrophysics Data System (ADS)

    Sugimoto, Toyonari; Fujiwara, Hideki; Noguchi, Satoru; Murata, Keizo

    2009-04-01

    The 2 : 1 cation radical salts of bent donor molecules of ethylenedithio-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDT-TTFVO), ethylenedithio-diselenadithiafulvalenoquinone-1,3-dithiolemethide (EDT-DSDTFVO), ethylenedithio-diselenadithiafulvalenothioquinone-1,3-diselenolemethide (EDT-DSDTFVSDS), ethylenedioxy-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDO-TTFVO) and ethylenedioxy-tetrathiafulvalenoquinone-1,3-diselenolemethide (EDO-TTFVODS) with FeX4- (X = Cl, Br) ions are prepared by electrocrystallization. The crystal structures of these salts are composed of alternately stacked donor molecule and magnetic anion layers. The band structures of the donor molecule layers are calculated using the overlap integrals between neighboring donor molecules and are compared with the observed electronic transport properties. The magnetic ordering of the Fe(III) d spins of FeX4- ions is determined from magnetization and heat capacity measurements. The magnetic ordering temperatures are estimated by considering a combination of a direct d-d interaction between the d spins and an indirect π-d interaction between the conduction π electron and the d spins, whose magnitudes are separately calculated from the crystal structures with an extended Hückel molecular orbital method. The occurrence of a π-d interaction is proved by the negative magnetoresistance, and the magnitude of magnetoresistance reflects the strength of the π-d interaction. The effect of pressure on the magnetoresistance is studied, and the result indicates that the magnitude of magnetoresistance increases, namely, the π-d interaction is enhanced with increasing pressure. From these experimental results it is shown that (EDT-TTFVO)2•FeBr4 is a ferromagnetic semiconductor, (EDT-DSDTFVO)2•FeX4 (X = Cl, Br) and (EDT-DSDTFVSDS)2•FeBr4 are metals exhibiting antiferromagnetic ordering of the d spins, and (EDO-TTFVO)2•FeCl4 and (EDO-TTFVODS)2•FeBr4•(DCE)0.5 (DCE =-dichloroethane) are genuine

  4. A novel integrated framework and improved methodology of computer-aided drug design.

    PubMed

    Chen, Calvin Yu-Chian

    2013-01-01

    Computer-aided drug design (CADD) is a critical initiating step of drug development, but a single model capable of covering all designing aspects remains to be elucidated. Hence, we developed a drug design modeling framework that integrates multiple approaches, including machine learning based quantitative structure-activity relationship (QSAR) analysis, 3D-QSAR, Bayesian network, pharmacophore modeling, and structure-based docking algorithm. Restrictions for each model were defined for improved individual and overall accuracy. An integration method was applied to join the results from each model to minimize bias and errors. In addition, the integrated model adopts both static and dynamic analysis to validate the intermolecular stabilities of the receptor-ligand conformation. The proposed protocol was applied to identifying HER2 inhibitors from traditional Chinese medicine (TCM) as an example for validating our new protocol. Eight potent leads were identified from six TCM sources. A joint validation system comprised of comparative molecular field analysis, comparative molecular similarity indices analysis, and molecular dynamics simulation further characterized the candidates into three potential binding conformations and validated the binding stability of each protein-ligand complex. The ligand pathway was also performed to predict the ligand "in" and "exit" from the binding site. In summary, we propose a novel systematic CADD methodology for the identification, analysis, and characterization of drug-like candidates.

  5. Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

    PubMed Central

    Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

  6. In silico simulations of tunneling barrier measurements for molecular orbital-mediated junctions: A molecular orbital theory approach to scanning tunneling microscopy

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

    Terryn, Raymond J.; Sriraman, Krishnan; Olson, Joel A., E-mail: jolson@fit.edu

    A new simulator for scanning tunneling microscopy (STM) is presented based on the linear combination of atomic orbitals molecular orbital (LCAO-MO) approximation for the effective tunneling Hamiltonian, which leads to the convolution integral when applied to the tip interaction with the sample. This approach intrinsically includes the structure of the STM tip. Through this mechanical emulation and the tip-inclusive convolution model, dI/dz images for molecular orbitals (which are closely associated with apparent barrier height, ϕ{sub ap}) are reported for the first time. For molecular adsorbates whose experimental topographic images correspond well to isolated-molecule quantum chemistry calculations, the simulator makes accuratemore » predictions, as illustrated by various cases. Distortions in these images due to the tip are shown to be in accord with those observed experimentally and predicted by other ab initio considerations of tip structure. Simulations of the tunneling current dI/dz images are in strong agreement with experiment. The theoretical framework provides a solid foundation which may be applied to LCAO cluster models of adsorbate–substrate systems, and is extendable to emulate several aspects of functional STM operation.« less

  7. Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

    PubMed

    Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

    2016-03-01

    Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

  8. Molecular aspects of cyst nematodes.

    PubMed

    Lilley, Catherine J; Atkinson, Howard J; Urwin, Peter E

    2005-11-01

    SUMMARY Taxonomy: Superkingdom Eukaryota; kingdom Metazoa; phylum Nematoda; class Chromadorea; order Tylenchida; suborder Tylenchina; superfamily Tylenchoidea; family Heteroderidae; subfamily Heteroderinae; main genera Heterodera and Globodera. Cyst nematodes comprise approximately 100 known species in six genera. They are pathogens of temperate, subtropical and tropical plant species and the host range of many species is narrow. The most economically important species are within the Globodera and Heterodera genera. Globodera pallida and G. rostochiensis are important pathogens of potato crops. There are many economic species in the Heterodera genus, including Heterodera glycines (soybean cyst nematode), H. avenae (cereal cyst nematode) and H. schachtii (sugar beet cyst nematode), the last of which attacks a range of Chenopodiaceae and Cruciferae, including Arabidopsis thaliana. Disease symptoms: Field symptoms of severe cyst nematode infection are often stunting, wilting and chlorosis, but considerable yield loss can occur without obvious symptoms. The only unique indicator of cyst nematode infection is the presence of adult female nematodes attached to host roots after several weeks of parasitism. Disease control: This is usually achieved by using integrated pest management involving cultural practices such as crop rotation, resistant cultivars if available and chemical control when economically justified.

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

    PubMed

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

    2013-12-01

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

  10. Fully 3D printed integrated reactor array for point-of-care molecular diagnostics.

    PubMed

    Kadimisetty, Karteek; Song, Jinzhao; Doto, Aoife M; Hwang, Young; Peng, Jing; Mauk, Michael G; Bushman, Frederic D; Gross, Robert; Jarvis, Joseph N; Liu, Changchun

    2018-06-30

    Molecular diagnostics that involve nucleic acid amplification tests (NAATs) are crucial for prevention and treatment of infectious diseases. In this study, we developed a simple, inexpensive, disposable, fully 3D printed microfluidic reactor array that is capable of carrying out extraction, concentration and isothermal amplification of nucleic acids in variety of body fluids. The method allows rapid molecular diagnostic tests for infectious diseases at point of care. A simple leak-proof polymerization strategy was developed to integrate flow-through nucleic acid isolation membranes into microfluidic devices, yielding a multifunctional diagnostic platform. Static coating technology was adopted to improve the biocompatibility of our 3D printed device. We demonstrated the suitability of our device for both end-point colorimetric qualitative detection and real-time fluorescence quantitative detection. We applied our diagnostic device to detection of Plasmodium falciparum in plasma samples and Neisseria meningitides in cerebrospinal fluid (CSF) samples by loop-mediated, isothermal amplification (LAMP) within 50 min. The detection limits were 100 fg for P. falciparum and 50 colony-forming unit (CFU) for N. meningitidis per reaction, which are comparable to that of benchtop instruments. This rapid and inexpensive 3D printed device has great potential for point-of-care molecular diagnosis of infectious disease in resource-limited settings. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. AN INTEGRATED PERSPECTIVE ON THE ASSESSMENT OF TECHNOLOGIES: INTEGRATE-HTA.

    PubMed

    Wahlster, Philip; Brereton, Louise; Burns, Jacob; Hofmann, Björn; Mozygemba, Kati; Oortwijn, Wija; Pfadenhauer, Lisa; Polus, Stephanie; Rehfuess, Eva; Schilling, Imke; van der Wilt, Gert Jan; Gerhardus, Ansgar

    2017-01-01

    Current health technology assessment (HTA) is not well equipped to assess complex technologies as insufficient attention is being paid to the diversity in patient characteristics and preferences, context, and implementation. Strategies to integrate these and several other aspects, such as ethical considerations, in a comprehensive assessment are missing. The aim of the European research project INTEGRATE-HTA was to develop a model for an integrated HTA of complex technologies. A multi-method, four-stage approach guided the development of the INTEGRATE-HTA Model: (i) definition of the different dimensions of information to be integrated, (ii) literature review of existing methods for integration, (iii) adjustment of concepts and methods for assessing distinct aspects of complex technologies in the frame of an integrated process, and (iv) application of the model in a case study and subsequent revisions. The INTEGRATE-HTA Model consists of five steps, each involving stakeholders: (i) definition of the technology and the objective of the HTA; (ii) development of a logic model to provide a structured overview of the technology and the system in which it is embedded; (iii) evidence assessment on effectiveness, economic, ethical, legal, and socio-cultural aspects, taking variability of participants, context, implementation issues, and their interactions into account; (iv) populating the logic model with the data generated in step 3; (v) structured process of decision-making. The INTEGRATE-HTA Model provides a structured process for integrated HTAs of complex technologies. Stakeholder involvement in all steps is essential as a means of ensuring relevance and meaningful interpretation of the evidence.

  12. Coherent coupling between Vanadyl Phthalocyanine spin ensemble and microwave photons: towards integration of molecular spin qubits into quantum circuits.

    PubMed

    Bonizzoni, C; Ghirri, A; Atzori, M; Sorace, L; Sessoli, R; Affronte, M

    2017-10-12

    Electron spins are ideal two-level systems that may couple with microwave photons so that, under specific conditions, coherent spin-photon states can be realized. This represents a fundamental step for the transfer and the manipulation of quantum information. Along with spin impurities in solids, molecular spins in concentrated phases have recently shown coherent dynamics under microwave stimuli. Here we show that it is possible to obtain high cooperativity regime between a molecular Vanadyl Phthalocyanine (VOPc) spin ensemble and a high quality factor superconducting YBa 2 Cu 3 O 7 (YBCO) coplanar resonator at 0.5 K. This demonstrates that molecular spin centers can be successfully integrated in hybrid quantum devices.

  13. [New aspects of the molecular effect of anti-arrhythmia agents].

    PubMed

    Honerjäger, P

    1990-04-01

    Excitation propagation is mediated by the brief opening of voltage-dependent Na-channels in the plasma membranes of cells of the conduction system and working myocardium. The refractory period is a function of the re-availability of the Na-channel for renewed opening. Most antiarrhythmic agents block cardiac Na-channels and, consequently, affect the desired refractory period prolongation. At the same time, however, dependent on the concentration and the substance, they slow conduction; an effect which can facilitate reentry excitation in the injured heart. The Na-channel blocking drugs, class I antiarrhythmic agents, are distinguished from the beta-receptor blockers, class II, repolarizing prolonging drugs, class III, and the cardiac Ca-channel blocking drugs (class IV) (Table 1). MOLECULAR STRUCTURE OF THE CARDIAC NA-CHANNEL: Voltage-dependent Na-channels which have been structurally elucidated to date are glycoprotein macromolecules of about 2000 amino acids with a molecular weight of about 260,000. Beginning at the amino terminal, four consecutive homologous domains can be differentiated which are composed of six transmembranous segments each. The terminal portion of the chain as well as the connecting segments between the domains appear intracellular. There are important relationships between the molecular structure and the function of the Na-channel (Figure 1). On comparison of the primary structures of neuronal and cardiac Na-channels, domains I to IV as well as the connecting segment between domains III and IV, are nearly identical. Homology in all of the remaining molecular regions, in contrast, is less than 70%. These segments as well as the differing structure of the four S5-S6 connecting chains may be responsible for the varying functional response of the cardiac Na-channels. MOLECULAR SITE OF ACTION OF ANTIARRHYTHMIC AGENTS AT THE CARDIAC NA-CHANNEL: Since most antiarrhythmic agents are weak bases with pK values between 7.5 and 9.5, in the physiologic

  14. A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction Networks

    PubMed Central

    Eissing, Thomas; Kuepfer, Lars; Becker, Corina; Block, Michael; Coboeken, Katrin; Gaub, Thomas; Goerlitz, Linus; Jaeger, Juergen; Loosen, Roland; Ludewig, Bernd; Meyer, Michaela; Niederalt, Christoph; Sevestre, Michael; Siegmund, Hans-Ulrich; Solodenko, Juri; Thelen, Kirstin; Telle, Ulrich; Weiss, Wolfgang; Wendl, Thomas; Willmann, Stefan; Lippert, Joerg

    2011-01-01

    Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multiscale by nature, project work, and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug–drug, or drug–metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach. PMID:21483730

  15. A DICOM-based 2nd generation Molecular Imaging Data Grid implementing the IHE XDS-i integration profile.

    PubMed

    Lee, Jasper; Zhang, Jianguo; Park, Ryan; Dagliyan, Grant; Liu, Brent; Huang, H K

    2012-07-01

    A Molecular Imaging Data Grid (MIDG) was developed to address current informatics challenges in archival, sharing, search, and distribution of preclinical imaging studies between animal imaging facilities and investigator sites. This manuscript presents a 2nd generation MIDG replacing the Globus Toolkit with a new system architecture that implements the IHE XDS-i integration profile. Implementation and evaluation were conducted using a 3-site interdisciplinary test-bed at the University of Southern California. The 2nd generation MIDG design architecture replaces the initial design's Globus Toolkit with dedicated web services and XML-based messaging for dedicated management and delivery of multi-modality DICOM imaging datasets. The Cross-enterprise Document Sharing for Imaging (XDS-i) integration profile from the field of enterprise radiology informatics was adopted into the MIDG design because streamlined image registration, management, and distribution dataflow are likewise needed in preclinical imaging informatics systems as in enterprise PACS application. Implementation of the MIDG is demonstrated at the University of Southern California Molecular Imaging Center (MIC) and two other sites with specified hardware, software, and network bandwidth. Evaluation of the MIDG involves data upload, download, and fault-tolerance testing scenarios using multi-modality animal imaging datasets collected at the USC Molecular Imaging Center. The upload, download, and fault-tolerance tests of the MIDG were performed multiple times using 12 collected animal study datasets. Upload and download times demonstrated reproducibility and improved real-world performance. Fault-tolerance tests showed that automated failover between Grid Node Servers has minimal impact on normal download times. Building upon the 1st generation concepts and experiences, the 2nd generation MIDG system improves accessibility of disparate animal-model molecular imaging datasets to users outside a molecular

  16. Molecular mechanisms of retroviral integration site selection

    PubMed Central

    Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

    2014-01-01

    Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

  17. Integrating the Ontological, Epistemological, and Sociocultural Aspects: A Holistic View of Teacher Education

    ERIC Educational Resources Information Center

    Huang, Teng

    2016-01-01

    The three aspects of teacher change--ontological, epistemological, and sociocultural--are traditionally regarded as independent. Usually only the epistemological aspect is highlighted in formal teacher education. In this paper, I argue that a holistic and interdependent view of these aspects is needed. Thus, this paper aims to explore the process…

  18. Affective Aspects of an Age-Integrated Water Exercise Program.

    ERIC Educational Resources Information Center

    Weiss, Caroline R.; Jamieson, Nancy B.

    1987-01-01

    Surveyed 88 female participants of community-based age-integrated water exercise program designed to enhance comfort and social interaction. Affective measures and observation of membership as a support group elicited few differences by age. Members endorsed having age integration in classes and there was little indication that subgroups of…

  19. Integrated ozone and biotreatment of pulp mill effluent and changes in biodegradability and molecular weight distribution of organic compounds.

    PubMed

    Bijan, Leila; Mohseni, Madjid

    2005-10-01

    The overall effectiveness of integrating ozonation with biological treatment on the biodegradability enhancement and recalcitrant organic matter (ROM) removal from pulp mill alkaline bleach plant effluent was investigated. Ozonation was performed in a semi-batch bubble column reactor at pH of 11 and 4.5. Batch biological treatment was conducted in shake flasks. Samples obtained during the treatments were monitored for BOD5, COD, TOC, and molecular weight distribution. At an ozone dosage of 0.7-0.8 mg O3/mL wastewater, integrated treatment showed about 30% higher TOC mineralization compared to individual ozonation or biotreatment. Ozone treatment enhanced the biodegradability of the effluent (monitored as 21% COD reduction and 13% BOD5 enhancement), allowing for a higher removal of pollutants. The conversion of high molecular weight (HMW) to low molecular weight (LMW) compounds was an important factor in the overall biodegradability enhancement of the alkaline effluent. The overall biodegradability of the LMW compounds did not change over the course of ozonation, but it increased from 5% to 50% (measured as COD removal) for the HMW portion. Ozonation at pH of 11 was more effective than that at pH of 4.5 in terms of generating more biodegradable compounds.

  20. QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts

    PubMed Central

    Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till; Stone, John E.; Phillips, James C.; Freddolino, Peter L.; Schulten, Klaus

    2016-01-01

    The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services. PMID:27216779

  1. QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts

    NASA Astrophysics Data System (ADS)

    Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till; Stone, John E.; Phillips, James C.; Freddolino, Peter L.; Schulten, Klaus

    2016-05-01

    The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services.

  2. Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia

    PubMed Central

    Xie, Duoli; Shi, Tieliu; Wen, Chengping

    2017-01-01

    Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients’ molecular features. Our method of formulating CMs based on patients’ stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization. PMID:28454110

  3. Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia.

    PubMed

    Huang, Lin; Li, Haichang; Xie, Duoli; Shi, Tieliu; Wen, Chengping

    2017-06-27

    Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients' molecular features. Our method of formulating CMs based on patients' stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization.

  4. Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure

    NASA Astrophysics Data System (ADS)

    Lippert, Ross A.; Predescu, Cristian; Ierardi, Douglas J.; Mackenzie, Kenneth M.; Eastwood, Michael P.; Dror, Ron O.; Shaw, David E.

    2013-10-01

    In molecular dynamics simulations, control over temperature and pressure is typically achieved by augmenting the original system with additional dynamical variables to create a thermostat and a barostat, respectively. These variables generally evolve on timescales much longer than those of particle motion, but typical integrator implementations update the additional variables along with the particle positions and momenta at each time step. We present a framework that replaces the traditional integration procedure with separate barostat, thermostat, and Newtonian particle motion updates, allowing thermostat and barostat updates to be applied infrequently. Such infrequent updates provide a particularly substantial performance advantage for simulations parallelized across many computer processors, because thermostat and barostat updates typically require communication among all processors. Infrequent updates can also improve accuracy by alleviating certain sources of error associated with limited-precision arithmetic. In addition, separating the barostat, thermostat, and particle motion update steps reduces certain truncation errors, bringing the time-average pressure closer to its target value. Finally, this framework, which we have implemented on both general-purpose and special-purpose hardware, reduces software complexity and improves software modularity.

  5. Automated Illustration of Molecular Flexibility.

    PubMed

    Bryden, A; Phillips, George N; Gleicher, M

    2012-01-01

    In this paper, we present an approach to creating illustrations of molecular flexibility using normal mode analysis (NMA). The output of NMA is a collection of points corresponding to the locations of atoms and associated motion vectors, where a vector for each point is known. Our approach abstracts the complex object and its motion by grouping the points, models the motion of each group as an affine velocity, and depicts the motion of each group by automatically choosing glyphs such as arrows. Affine exponentials allow the extrapolation of nonlinear effects such as near rotations and spirals from the linear velocities. Our approach automatically groups points by finding sets of neighboring points whose motions fit the motion model. The geometry and motion models for each group are used to determine glyphs that depict the motion, with various aspects of the motion mapped to each glyph. We evaluated the utility of our system in real work done by structural biologists both by utilizing it in our own structural biology work and quantitatively measuring its usefulness on a set of known protein conformation changes. Additionally, in order to allow ourselves and our collaborators to effectively use our techniques we integrated our system with commonly used tools for molecular visualization.

  6. Molecular Robots Obeying Asimov's Three Laws of Robotics.

    PubMed

    Kaminka, Gal A; Spokoini-Stern, Rachel; Amir, Yaniv; Agmon, Noa; Bachelet, Ido

    2017-01-01

    Asimov's three laws of robotics, which were shaped in the literary work of Isaac Asimov (1920-1992) and others, define a crucial code of behavior that fictional autonomous robots must obey as a condition for their integration into human society. While, general implementation of these laws in robots is widely considered impractical, limited-scope versions have been demonstrated and have proven useful in spurring scientific debate on aspects of safety and autonomy in robots and intelligent systems. In this work, we use Asimov's laws to examine these notions in molecular robots fabricated from DNA origami. We successfully programmed these robots to obey, by means of interactions between individual robots in a large population, an appropriately scoped variant of Asimov's laws, and even emulate the key scenario from Asimov's story "Runaround," in which a fictional robot gets into trouble despite adhering to the laws. Our findings show that abstract, complex notions can be encoded and implemented at the molecular scale, when we understand robots on this scale on the basis of their interactions.

  7. Accelerating ab initio path integral molecular dynamics with multilevel sampling of potential surface

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

    Geng, Hua Y., E-mail: huay.geng@gmail.com; Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853

    A multilevel approach to sample the potential energy surface in a path integral formalism is proposed. The purpose is to reduce the required number of ab initio evaluations of energy and forces in ab initio path integral molecular dynamics (AI-PIMD) simulation, without compromising the overall accuracy. To validate the method, the internal energy and free energy of an Einstein crystal are calculated and compared with the analytical solutions. As a preliminary application, we assess the performance of the method in a realistic model—the FCC phase of dense atomic hydrogen, in which the calculated result shows that the acceleration rate ismore » about 3 to 4-fold for a two-level implementation, and can be increased up to 10 times if extrapolation is used. With only 16 beads used for the ab initio potential sampling, this method gives a well converged internal energy. The residual error in pressure is just about 3 GPa, whereas it is about 20 GPa for a plain AI-PIMD calculation with the same number of beads. The vibrational free energy of the FCC phase of dense hydrogen at 300 K is also calculated with an AI-PIMD thermodynamic integration method, which gives a result of about 0.51 eV/proton at a density of r{sub s}=0.912.« less

  8. Path-integral molecular dynamics simulations of hydrated hydrogen chloride cluster HCl(H 2O) 4 on a semiempirical potential energy surface

    NASA Astrophysics Data System (ADS)

    Takayanagi, Toshiyuki; Takahashi, Kenta; Kakizaki, Akira; Shiga, Motoyuki; Tachikawa, Masanori

    2009-04-01

    Path-integral molecular dynamics simulations for the HCl(H 2O) 4 cluster have been performed on the ground-state potential energy surface directly obtained on-the-fly from semiempirical PM3-MAIS molecular orbital calculations. It is found that the HCl(H 2O) 4 cluster has structural rearrangement above the temperature of 300 K showing a liquid-like behavior. Quantum mechanical fluctuation of hydrogen nuclei plays a significant role in structural arrangement processes in this cluster.

  9. High-aspect-ratio and highly ordered 15-nm porous alumina templates.

    PubMed

    Martín, Jaime; Manzano, Cristina V; Caballero-Calero, Olga; Martín-González, Marisol

    2013-01-01

    Ordered anodic aluminum oxide (AAO) templates with pores <15 nm in diameter and an aspect ratio (length-to-diameter ratio) above 3 × 10(3) have been fabricated using a nonlithographic approach; specifically, by anodizing aluminum in an ethylene-glycol-containing sulfuric acid electrolyte. The pores are the smallest in diameter reported for a self-ordered AAO without pore aspect-ratio limitations and good ordering, which opens up the possibility of obtaining nanowire arrays in the quantum confinement regime that is of interest for efficient thermoelectric generators. The effect of the ethylene glycol addition on both the pore diameter and the ordering is evaluated and discussed. Moreover, 15-nm-diameter Bi(2)Te(3) and poly(3-hexyl thiophene) (P3HT) nanowires have been prepared using these AAO templates. As known, Bi(2)Te(3) is currently the most efficient thermoelectric bulk material for room-temperature operations and, according with theory, its Seebeck coefficient should be increased when it is confined to nanowires with diameters close to 10 nm. On the other hand, P3HT is one of the main candidates for integrating organic photovoltaic and thermoelectric devices, and its properties are also proposed to increase when it is confined to nanoscale structures, mainly due to molecular orientation effects.

  10. Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins

    NASA Astrophysics Data System (ADS)

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-01

    The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm- 1 and 1545 cm- 1, respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

  11. Molecular Modeling of Estrogen Receptor Using Molecular Operating Environment

    ERIC Educational Resources Information Center

    Roy, Urmi; Luck, Linda A.

    2007-01-01

    Molecular modeling is pervasive in the pharmaceutical industry that employs many of our students from Biology, Chemistry and the interdisciplinary majors. To expose our students to this important aspect of their education we have incorporated a set of tutorials in our Biochemistry class. The present article describes one of our tutorials where…

  12. Integrated Translatome and Proteome: Approach for Accurate Portraying of Widespread Multifunctional Aspects of Trichoderma

    PubMed Central

    Sharma, Vivek; Salwan, Richa; Sharma, P. N.; Gulati, Arvind

    2017-01-01

    Genome-wide studies of transcripts expression help in systematic monitoring of genes and allow targeting of candidate genes for future research. In contrast to relatively stable genomic data, the expression of genes is dynamic and regulated both at time and space level at different level in. The variation in the rate of translation is specific for each protein. Both the inherent nature of an mRNA molecule to be translated and the external environmental stimuli can affect the efficiency of the translation process. In biocontrol agents (BCAs), the molecular response at translational level may represents noise-like response of absolute transcript level and an adaptive response to physiological and pathological situations representing subset of mRNAs population actively translated in a cell. The molecular responses of biocontrol are complex and involve multistage regulation of number of genes. The use of high-throughput techniques has led to rapid increase in volume of transcriptomics data of Trichoderma. In general, almost half of the variations of transcriptome and protein level are due to translational control. Thus, studies are required to integrate raw information from different “omics” approaches for accurate depiction of translational response of BCAs in interaction with plants and plant pathogens. The studies on translational status of only active mRNAs bridging with proteome data will help in accurate characterization of only a subset of mRNAs actively engaged in translation. This review highlights the associated bottlenecks and use of state-of-the-art procedures in addressing the gap to accelerate future accomplishment of biocontrol mechanisms. PMID:28900417

  13. Molecular markers: a potential resource for ginger genetic diversity studies.

    PubMed

    Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

    2016-12-01

    Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

  14. Integrative transcriptome, proteome, phosphoproteome and genetic mapping reveals new aspects in a fiberless mutant of cotton

    PubMed Central

    Ma, Qi-Feng; Wu, Chun-Hui; Wu, Man; Pei, Wen-Feng; Li, Xing-Li; Wang, Wen-Kui; Zhang, Jinfa; Yu, Ji-Wen; Yu, Shu-Xun

    2016-01-01

    To investigate the molecular mechanisms of fiber initiation in cotton (Gossypium spp.), an integrated approach combining transcriptome, iTRAQ-based proteome and genetic mapping was taken to compare the ovules of the Xuzhou 142 wild type (WT) with its fuzzless-lintless (fl) mutant at −3 and 0 day post-anthesis. A total of 1,953 mRNAs, 187 proteins, and 131 phosphoproteins were differentially expressed (DE) between WT and fl, and the levels of transcripts and their encoded proteins and phosphoproteins were highly congruent. A functional analysis suggested that the abundance of proteins were mainly involved in amino sugar, nucleotide sugar and fatty acid metabolism, one carbon pool for folate metabolism and flavonoid biosynthesis. qRT-PCR, Western blotting, and enzymatic assays were performed to confirm the regulation of these transcripts and proteins. A molecular mapping located the lintless gene li3 in the fl mutant on chromosome 26 for the first time. A further in-silico physical mapping of DE genes with sequence variations between fl and WT identified one and four candidate genes in the li3 and n2 regions, respectively. Taken together, the transcript abundance, phosphorylation status of proteins at the fiber initiation stage and candidate genes have provided insights into regulatory processes underlying cotton fiber initiation. PMID:27075604

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

    PubMed Central

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

    2012-01-01

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

  16. In-Cardiome: integrated knowledgebase for coronary artery disease enabling translational research

    PubMed Central

    Sharma, Ankit; Deshpande, Vrushali; Ghatge, Madankumar

    2017-01-01

    Abstract Coronary artery disease (CAD) is a leading cause of death worldwide. Prevention, diagnosis and clinical interventions are dependent on the conventional risk factors like hypertension, diabetes and obesity. However, these conventional risk factors do not completely identify high risk individuals. One major hurdle in the improvement of diagnosis and treatment for CAD is the lack of integration of knowledge from different areas of research like molecular, clinical and drug development. In order to provide comprehensive information from hitherto dispersed data, we developed an integrative knowledgebase called “In-Cardiome or Integrated Cardiome” for all the stake holders in healthcare such as scientists, clinicians and pharmaceutical companies. It is created by integrating 16 different data sources, 995 curated genes classified into 12 different functional categories associated with disease, 1204 completed clinical trials, 12 therapy or drug classifications with 62 approved drugs and drug target networks. This knowledgebase gives the most needed opportunity to understand the disease process and therapeutic impact along with gene expression data from both animal models and patients. The data is classified into three different search categories functional groups, risk factors and therapy/drug based classes. One more unique aspect of In-Cardiome is integration of clinical data of 10,217 subject data from our ongoing Indian Atherosclerosis Research Study (IARS) (6357 unaffected and 3860 CAD affected). IARS data showing demographics and associations of individual and combinations of risk factors in Indian population along with molecular information will enable better translational and drug development research. Database URL www.tri-incardiome.org PMID:29220465

  17. Self assembled monolayers on silicon for molecular electronics.

    PubMed

    Aswal, D K; Lenfant, S; Guerin, D; Yakhmi, J V; Vuillaume, D

    2006-05-24

    We present an overview of various aspects of the self-assembly of organic monolayers on silicon substrates for molecular electronics applications. Different chemical strategies employed for grafting the self-assembled monolayers (SAMs) of alkanes having different chain lengths on native oxide of Si or on bare Si have been reviewed. The utility of different characterization techniques in determination of the thickness, molecular ordering and orientation, surface coverage, growth kinetics and chemical composition of the SAMs has been discussed by choosing appropriate examples. The metal counterelectrodes are an integral part of SAMs for measuring their electrical properties as well as using them for molecular electronic devices. A brief discussion on the variety of options available for the deposition of metal counterelectrodes, that is, soft metal contacts, vapor deposition and soft lithography, has been presented. Various theoretical models, namely, tunneling (direct and Fowler-Nordheim), thermionic emission, Poole-Frenkel emission and hopping conduction, used for explaining the electronic transport in dielectric SAMs have been outlined and, some experimental data on alkane SAMs have been analyzed using these models. It has been found that short alkyl chains show excellent agreement with tunneling models; while more experimental data on long alkyl chains are required to understand their transport mechanism(s). Finally, the concepts and realization of various molecular electronic components, that is, diodes, resonant tunnel diodes, memories and transistors, based on appropriate architecture of SAMs comprising of alkyl chains (sigma- molecule) and conjugated molecules (pi-molecule) have been presented.

  18. Construction, database integration, and application of an Oenothera EST library.

    PubMed

    Mrácek, Jaroslav; Greiner, Stephan; Cho, Won Kyong; Rauwolf, Uwe; Braun, Martha; Umate, Pavan; Altstätter, Johannes; Stoppel, Rhea; Mlcochová, Lada; Silber, Martina V; Volz, Stefanie M; White, Sarah; Selmeier, Renate; Rudd, Stephen; Herrmann, Reinhold G; Meurer, Jörg

    2006-09-01

    Coevolution of cellular genetic compartments is a fundamental aspect in eukaryotic genome evolution that becomes apparent in serious developmental disturbances after interspecific organelle exchanges. The genus Oenothera represents a unique, at present the only available, resource to study the role of the compartmentalized plant genome in diversification of populations and speciation processes. An integrated approach involving cDNA cloning, EST sequencing, and bioinformatic data mining was chosen using Oenothera elata with the genetic constitution nuclear genome AA with plastome type I. The Gene Ontology system grouped 1621 unique gene products into 17 different functional categories. Application of arrays generated from a selected fraction of ESTs revealed significantly differing expression profiles among closely related Oenothera species possessing the potential to generate fertile and incompatible plastid/nuclear hybrids (hybrid bleaching). Furthermore, the EST library provides a valuable source of PCR-based polymorphic molecular markers that are instrumental for genotyping and molecular mapping approaches.

  19. Integration and scaling of UV-B radiation effects on plants: from molecular interactions to whole plant responses.

    PubMed

    Suchar, Vasile Alexandru; Robberecht, Ronald

    2016-07-01

    A process based model integrating the effects of UV-B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed that UV-B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermal UV-B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions between UV-B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2-5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increased UV-B radiation through molecular level processes and their consequences to whole plant growth and development.

  20. Structural and dynamical aspects of Streptococcus gordonii FabH through molecular docking and MD simulations.

    PubMed

    Shamim, Amen; Abbasi, Sumra Wajid; Azam, Syed Sikander

    2015-07-01

    β-Ketoacyl-ACP-synthase III (FabH or KAS III) has become an attractive target for the development of new antibacterial agents which can overcome the multidrug resistance. Unraveling the fatty acid biosynthesis (FAB) metabolic pathway and understanding structural coordinates of FabH will provide valuable insights to target Streptococcus gordonii for curing oral infection. In this study, we designed inhibitors against therapeutic target FabH, in order to block the FAB pathway. As compared to other targets, FabH has more interactions with other proteins, located on the leading strand with higher codon adaptation index value and associated with lipid metabolism category of COG. Current study aims to gain in silico insights into the structural and dynamical aspect of S. gordonii FabH via molecular docking and molecular dynamics (MD) simulations. The FabH protein is catalytically active in dimerization while it can lock in monomeric state. Current study highlights two residues Pro88 and Leu315 that are close to each other by dimerization. The active site of FabH is composed of the catalytic triad formed by residues Cys112, His249, and Asn279 in which Cys112 is involved in acetyl transfer, while His249 and Asn279 play an active role in decarboxylation. Docking analysis revealed that among the studied compounds, methyl-CoA disulfide has highest GOLD score (82.75), binding affinity (-11 kcal/mol) and exhibited consistently better interactions. During MD simulations, the FabH structure remained stable with the average RMSD value of 1.7 Å and 1.6 Å for undocked protein and docked complex, respectively. Further, crucial hydrogen bonding of the conserved catalytic triad for exhibiting high affinity between the FabH protein and ligand is observed by RDF analysis. The MD simulation results clearly demonstrated that binding of the inhibitor with S. gordonii FabH enhanced the structure and stabilized the dimeric FabH protein. Therefore, the inhibitor has the potential to become

  1. Sublethal toxicity of Roundup to immunological and molecular aspects of Biomphalaria alexandrina to Schistosoma mansoni infection.

    PubMed

    Mohamed, Azza H

    2011-05-01

    The present study was performed to elucidate the cellular mechanisms of Biomphalaria alexandrina snails hemocytes against sublethal concentration (10 mg/L) of herbicide Roundup (48% Glyphosate) and/or Schistosoma mansoni infection during 7 days of exposure. Obtained results indicated that herbicide treatment and/or infection led to significant increase (P<0.05) in total hemocytes count during exposure period. Examination of hemocytes monolayers resulted in observation of 3 morphologically different cell types, round small, hyalinocytes and spreading hemocytes. Spreading hemocytes are the dominant, more responsive and highly phagocytic cell type in all experimental groups. Moreover, the exposure to herbicide, infection or both together led to a significant increase (P<0.05) of in vitro phagocytic activity against yeast cells during 7 days of exposure. In addition, flow cytometric analysis of cell cycle and comet assay, resulted in DNA damage in B. alexandrina hemocytes exposed to herbicide and/or S. mansoni infection when compared to control group. The immunological responses as well as molecular aspects in B. alexandrina snails have been proposed as biomarkers of exposure to environmental pollutants. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins.

    PubMed

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-05

    The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm(-1) and 1545 cm(-1), respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Human papillomavirus molecular biology.

    PubMed

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Aspects of seasonality.

    PubMed

    Battey, N H

    2000-11-01

    The seasons are astronomical, astrological, meteorological, biological, and agricultural. From a perspective outside the biological sciences, the questions of interest about plant seasonality are linked to this wider context. In this review I try to see flowering time, as one important aspect of seasonality, from an outsider's point of view, and describe what is known about it in different types of plants. What is known about it is conditioned by what particular scientists have asked about it, so the variety of approaches to seasonality is another point of emphasis. Detailed consideration is given to flowering seasonality in perennials compared with annuals, and both molecular and whole plant perspectives are presented.

  5. Double path integral method for obtaining the mobility of the one-dimensional charge transport in molecular chain.

    PubMed

    Yoo-Kong, Sikarin; Liewrian, Watchara

    2015-12-01

    We report on a theoretical investigation concerning the polaronic effect on the transport properties of a charge carrier in a one-dimensional molecular chain. Our technique is based on the Feynman's path integral approach. Analytical expressions for the frequency-dependent mobility and effective mass of the carrier are obtained as functions of electron-phonon coupling. The result exhibits the crossover from a nearly free particle to a heavily trapped particle. We find that the mobility depends on temperature and decreases exponentially with increasing temperature at low temperature. It exhibits large polaronic-like behaviour in the case of weak electron-phonon coupling. These results agree with the phase transition (A.S. Mishchenko et al., Phys. Rev. Lett. 114, 146401 (2015)) of transport phenomena related to polaron motion in the molecular chain.

  6. Pathogenesis of leptospirosis: cellular and molecular aspects.

    PubMed

    Adler, Ben

    2014-08-27

    Leptospirosis is arguably the most widespread zoonosis; it is also a major cause of economic loss in production animals worldwide. At the level of the host animal or human, the progression of infection and the onset of disease are well documented. However, the mechanisms of pathogenesis at the cellular and molecular level remain poorly understood, mainly as a result of the lack of modern genetic tools for mutagenesis of pathogenic Leptospira spp. The recent development of transposon mutagenesis and the construction of a very small number of directed leptospiral mutants have identified a limited number of essential virulence factors. Perhaps surprisingly, many leptospiral proteins with characteristics consistent with a role in virulence have been shown to not be required for virulence in animal models, consistent with a high degree of functional redundancy in pathogenic Leptospira. A large number of putative adhesins has been reported in Leptospira, which interact with a range of host tissue components; however, almost none of these have been genetically confirmed as having an essential role in pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. The Warburg effect: molecular aspects and therapeutic possibilities.

    PubMed

    Ngo, Hanh; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

    2015-04-01

    It has been about nine decades since the proposal of Otto Warburg on the metabolism of cancer cells. Unlike normal cells which undergo glycolysis and oxidative phosphorylation in the presence of oxygen, proliferating and cancer cells exhibit an increased uptake of glucose and increased rate of glycolysis and predominantly undergo lactic acid fermentation. Whether this phenomenon is the consequence of genetic dysregulation in cancer or is the cause of cancer still remains unknown. However, there is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review. Dichloroacetate and 3-bromopyruvate are among the substances that have been studied as potential cancer therapies. With our expanding knowledge of cellular metabolism, therapies targeting the Warburg effect appear very promising. This review discusses different aspects of these emerging therapies.

  8. The molecular circuitry of brassinosteroid signaling.

    PubMed

    Belkhadir, Youssef; Jaillais, Yvon

    2015-04-01

    Because they are tethered in space, plants have to make the most of their local growth environment. In order to grow in an ever-changing environment, plants constantly remodel their shapes. This adaptive attribute requires the orchestration of complex environmental signals at the cellular and organismal levels. A battery of small molecules, classically known as phytohormones, allows plants to change their body plan by using highly integrated signaling networks and transcriptional cascades. Amongst these hormones, brassinosteroids (BRs), the polyhydroxylated steroid of plants, influence plant responsiveness to the local environment and exquisitely promote, or interfere with, many aspects of plant development. The molecular circuits that wire steroid signals at the cell surface to the promoters of thousands of genes in the nucleus have been defined in the past decade. This review recapitulates how the transduction of BR signals impacts the temporally unfolding programs of plant growth. First, we summarize the paradigmatic BR signaling pathway acting primarily in cellular expansion. Secondly, we describe the current wiring diagram and the temporal dynamics of the BR signal transduction network. And finally we provide an overview of how key players in BR signaling act as molecular gates to transduce BR signals onto other signaling pathways. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  9. Oil spill vulnerability assessment integrating physical, biological and socio-economical aspects: application to the Cantabrian coast (Bay of Biscay, Spain).

    PubMed

    Castanedo, S; Juanes, J A; Medina, R; Puente, A; Fernandez, F; Olabarrieta, M; Pombo, C

    2009-10-01

    A methodology has been developed to carry out an integrated oil spill vulnerability index, V, for coastal environments. This index takes into account the main physical, biological and socio-economical characteristics by means of three intermediate indexes. Three different integration methods (worst-case, average and survey-based) along with ESI-based vulnerability scores, V(ESI), proposed for the Cantabrian coast during the Prestige oil spill, have been analyzed and compared in terms of agreement between the classifications obtained with each one for this coastal area. Results of this study indicate that the use of the worst-case index, V(R), leads to a conservative ranking, with a very poor discrimination which is not helpful in coastal oil spill risk management. Due to the homogeneity of this coastal stretch, the rest of the methods, V(I), V(M) and V(ESI), provide similar classifications. However, V(M) and V(I) give more flexibility allowing three indexes for each coastal segment and including socio-economic aspects. Finally, the V(I) procedure is proposed here as the more advisable as using this index promotes the public participation that is a key element in the implementation of Integrated Coastal Zone Management (IZCM).

  10. Technical aspects of cardiac PET/MRI.

    PubMed

    Masuda, Atsuro; Nemoto, Ayaka; Takeishi, Yasuchika

    2018-06-01

    PET/MRI is a novel modality that enables to combine PET and MR images, and has significant potential to evaluate various cardiac diseases through the combination of PET molecular imaging and MRI functional imaging. Precise management of technical issues, however, is necessary for cardiac PET/MRI. This article describes several technical points, including patient preparation, MR attenuation correction, parallel acquisition of PET with MRI, clinical aspects, and image quality control.

  11. [Integration of clinical and biological data in clinical practice using bioinformatics].

    PubMed

    Coltell, Oscar; Arregui, María; Fabregat, Antonio; Portolés, Olga

    2008-05-01

    The aim of our work is to describe essential aspects of Medical Informatics, Bioinformatics and Biomedical Informatics, that are used in biomedical research and clinical practice. These disciplines have emerged from the need to find new scientific and technical approaches to manage, store, analyze and report data generated in clinical practice and molecular biology and other medical specialties. It can be also useful to integrate research information generated in different areas of health care. Moreover, these disciplines are interdisciplinary and integrative, two key features not shared by other areas of medical knowledge. Finally, when Bioinformatics and Biomedical Informatics approach to medical investigation and practice are applied, a new discipline, called Clinical Bioinformatics, emerges. The latter requires a specific training program to create a new professional profile. We have not been able to find a specific training program in Clinical Bioinformatics in Spain.

  12. Molecular Studies of HTLV-1 Replication: An Update

    PubMed Central

    Martin, Jessica L.; Maldonado, José O.; Mueller, Joachim D.; Zhang, Wei; Mansky, Louis M.

    2016-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead to a variety of neurological pathologies, including HTLV-1-associated-myelopathy/tropical spastic paraparesis (HAM/TSP). The ability to treat the aggressive ATL subtypes remains inadequate. HTLV-1 replicates by (1) an infectious cycle involving virus budding and infection of new permissive target cells and (2) mitotic division of cells harboring an integrated provirus. Virus replication initiates host antiviral immunity and the checkpoint control of cell proliferation, but HTLV-1 has evolved elegant strategies to counteract these host defense mechanisms to allow for virus persistence. The study of the molecular biology of HTLV-1 replication has provided crucial information for understanding HTLV-1 replication as well as aspects of viral replication that are shared between HTLV-1 and human immunodeficiency virus type 1 (HIV-1). Here in this review, we discuss the various stages of the virus replication cycle—both foundational knowledge as well as current updates of ongoing research that is important for understanding HTLV-1 molecular pathogenesis as well as in developing novel therapeutic strategies. PMID:26828513

  13. Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

    PubMed Central

    Liu, Guangming; Wang, Yiwei; Zhao, Pengyao; Zhu, Yizhun; Yang, Xiaohan; Zheng, Tiezheng; Zhou, Xuezhong; Jin, Weilin; Sun, Changkai

    2017-01-01

    Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., “presynaptic nicotinic acetylcholine receptors”, “signaling by insulin receptor”). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy. PMID:28388656

  14. Molecular aspects of melatonin (MLT)-mediated therapeutic effects.

    PubMed

    Tuli, Hardeep Singh; Kashyap, Dharambir; Sharma, Anil K; Sandhu, Sardul Singh

    2015-08-15

    Hormones are a class of molecules, which mediate their effects by regulating a variety of signalling pathways. Melatonin (N-acetyl-5-methoxytryptamine), a pineal gland hormone, is one among the categories of compounds having various therapeutic and pharmacological effects. Melatonin has many intracellular as well as extracellular targets including apoptosis, metastasis, angiogenesis and inflammatory pathways. Gene-profile studies have further established its antagonist effect on the various genes involved in the tumour progression, neurodegeneration and ageing. It has also been known to reduce the toxicity induced by chemotherapeutic agents in advanced stages of tumour. The present review extensively describes the molecular interactions of melatonin with various recognized cellular targets, which may lead the scientific community to propose novel therapeutic strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Molecular aspects of stress-gene regulation during spaceflight

    NASA Technical Reports Server (NTRS)

    Paul, Anna-Lisa; Ferl, Robert J.

    2002-01-01

    Spaceflight-associated stress has been the topic of investigation since the first terrestrial organisms were exposed to this unique environment. Organisms that evolved under the selection pressures of earth-normal environments can perceive spaceflight as a stress, either directly because gravity influences an intrinsic biological process, or indirectly because of secondary effects imparted by spaceflight upon environmental conditions. Different organisms and even different organs within an organism adapt to a spaceflight environment with a diversity of tactics. Plants are keenly sensitive to gravity for directed development, and are also sensitive to other stresses associated with closed-system spaceflight environments. Within the past decade, the tools of molecular biology have begun to provide a sophisticated evaluation of spaceflight-associated stress and the genetic responses that accompany metabolic adaptation to spaceflight.

  16. Equilibrium fractionation of H and O isotopes in water from path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Pinilla, Carlos; Blanchard, Marc; Balan, Etienne; Ferlat, Guillaume; Vuilleumier, Rodolphe; Mauri, Francesco

    2014-06-01

    The equilibrium fractionation factor between two phases is of importance for the understanding of many planetary and environmental processes. Although thermodynamic equilibrium can be achieved between minerals at high temperature, many natural processes involve reactions between liquids or aqueous solutions and solids. For crystals, the fractionation factor α can be theoretically determined using a statistical thermodynamic approach based on the vibrational properties of the phases. These calculations are mostly performed in the harmonic approximation, using empirical or ab-initio force fields. In the case of aperiodic and dynamic systems such as liquids or solutions, similar calculations can be done using finite-size molecular clusters or snapshots obtained from molecular dynamics (MD) runs. It is however difficult to assess the effect of these approximate models on the isotopic fractionation properties. In this work we present a systematic study of the calculation of the D/H and 18O/16O equilibrium fractionation factors in water for the liquid/vapour and ice/vapour phases using several levels of theory within the simulations. Namely, we use a thermodynamic integration approach based on Path Integral MD calculations (PIMD) and an empirical potential model of water. Compared with standard MD, PIMD takes into account quantum effects in the thermodynamic modeling of systems and the exact fractionation factor for a given potential can be obtained. We compare these exact results with those of modeling strategies usually used, which involve the mapping of the quantum system on its harmonic counterpart. The results show the importance of including configurational disorder for the estimation of isotope fractionation in liquid phases. In addition, the convergence of the fractionation factor as a function of parameters such as the size of the simulated system and multiple isotope substitution is analyzed, showing that isotope fractionation is essentially a local effect in

  17. Actin Immobilization on Chitin for Purifying Myosin II: A Laboratory Exercise That Integrates Concepts of Molecular Cell Biology and Protein Chemistry

    ERIC Educational Resources Information Center

    de Souza, Marcelle Gomes; Grossi, Andre Luiz; Pereira, Elisangela Lima Bastos; da Cruz, Carolina Oliveira; Mendes, Fernanda Machado; Cameron, Luiz Claudio; Paiva, Carmen Lucia Antao

    2008-01-01

    This article presents our experience on teaching biochemical sciences through an innovative approach that integrates concepts of molecular cell biology and protein chemistry. This original laboratory exercise is based on the preparation of an affinity chromatography column containing F-actin molecules immobilized on chitin particles for purifying…

  18. Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela.

    PubMed

    Lima-Martínez, Marcos M; Paoli, Mariela; Vázquez-Cárdenas, Alejandra; Magaña-Torres, María Teresa; Guevara, Ornella; Muñoz, María Carolina; Parrilla-Alvarez, Alberto; Márquez, Yuliangelys; Medeiros, Ana; Bourbon, Mafalda

    2017-10-01

    To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Molecular Pathology Informatics.

    PubMed

    Roy, Somak

    2015-06-01

    Molecular informatics (MI) is an evolving discipline that will support the dynamic landscape of molecular pathology and personalized medicine. MI provides a fertile ground for development of clinical solutions to bridge the gap between clinical informatics and bioinformatics. Rapid adoption of next generation sequencing (NGS) in the clinical arena has triggered major endeavors in MI that are expected to bring a paradigm shift in the practice of pathology. This brief review presents a broad overview of various aspects of MI, particularly in the context of NGS based testing. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Integrated structural biology and molecular ecology of N-cycling enzymes from ammonia-oxidizing archaea

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

    Tolar, Bradley B.; Herrmann, Jonathan; Bargar, John R.

    In this paper, knowledge of the molecular ecology and environmental determinants of ammonia-oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N-cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowlede of key N-cycling enzymes from ecologically-relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia-oxidizing organisms, particularly uncultivated Thaumarchaeota, though (meta)genome-driven structural biology of the enzymes ammonia monooxygenase (AMO) andmore » nitrite reductase (NirK).« less

  1. Integrated structural biology and molecular ecology of N-cycling enzymes from ammonia-oxidizing archaea

    DOE PAGES

    Tolar, Bradley B.; Herrmann, Jonathan; Bargar, John R.; ...

    2017-07-05

    In this paper, knowledge of the molecular ecology and environmental determinants of ammonia-oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N-cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowlede of key N-cycling enzymes from ecologically-relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia-oxidizing organisms, particularly uncultivated Thaumarchaeota, though (meta)genome-driven structural biology of the enzymes ammonia monooxygenase (AMO) andmore » nitrite reductase (NirK).« less

  2. Integrated structural biology and molecular ecology of N-cycling enzymes from ammonia-oxidizing archaea.

    PubMed

    Tolar, Bradley B; Herrmann, Jonathan; Bargar, John R; van den Bedem, Henry; Wakatsuki, Soichi; Francis, Christopher A

    2017-10-01

    Knowledge of the molecular ecology and environmental determinants of ammonia-oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N-cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowledge of key N-cycling enzymes from ecologically relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia-oxidizing organisms, particularly uncultivated Thaumarchaeota, through (meta)genome-driven structural biology of the enzymes ammonia monooxygenase (AMO) and nitrite reductase (NirK). © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. [Advance in molecular biology of Dendrobium (Orchidaceae)].

    PubMed

    Li, Qing; Li, Biao; Guo, Shun-Xing

    2016-08-01

    With the development of molecular biology, the process in molecular biology research of Dendrobium is going fast. Not only did it provide new ways to identify Dendrobium quickly, reveal the genetic diversity and relationship of Dendrobium, but also lay the vital foundation for explaining the mechanism of Dendrobium growth and metabolism. The present paper reviews the recent process in molecular biology research of Dendrobium from three aspects, including molecular identification, genetic diversity and functional genes. And this review will facilitate the development of this research area and Dendrobium. Copyright© by the Chinese Pharmaceutical Association.

  4. Design and construction of a first-generation high-throughput integrated robotic molecular biology platform for bioenergy applications.

    PubMed

    Hughes, Stephen R; Butt, Tauseef R; Bartolett, Scott; Riedmuller, Steven B; Farrelly, Philip

    2011-08-01

    The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. High-throughput integrated robotic molecular biology platforms that have the capacity to rapidly clone and express heterologous gene open reading frames in bacteria and yeast and to screen large numbers of expressed proteins for optimized function are an important technology for improving microbial strains for biofuel production. The process involves the production of full-length complementary DNA libraries as a source of plasmid-based clones to express the desired proteins in active form for determination of their functions. Proteins that were identified by high-throughput screening as having desired characteristics are overexpressed in microbes to enable them to perform functions that will allow more cost-effective and sustainable production of biofuels. Because the plasmid libraries are composed of several thousand unique genes, automation of the process is essential. This review describes the design and implementation of an automated integrated programmable robotic workcell capable of producing complementary DNA libraries, colony picking, isolating plasmid DNA, transforming yeast and bacteria, expressing protein, and performing appropriate functional assays. These operations will allow tailoring microbial strains to use renewable feedstocks for production of biofuels, bioderived chemicals, fertilizers, and other coproducts for profitable and sustainable biorefineries. Published by Elsevier Inc.

  5. Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets.

    PubMed

    Van Laere, Steven J; Ueno, Naoto T; Finetti, Pascal; Vermeulen, Peter; Lucci, Anthony; Robertson, Fredika M; Marsan, Melike; Iwamoto, Takayuki; Krishnamurthy, Savitri; Masuda, Hiroko; van Dam, Peter; Woodward, Wendy A; Viens, Patrice; Cristofanilli, Massimo; Birnbaum, Daniel; Dirix, Luc; Reuben, James M; Bertucci, François

    2013-09-01

    Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported. Affymetrix profiles (HGU133-series) from 137 patients with IBC and 252 patients with non-IBC (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according to the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway, and transcription factor activation. Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (P<0.001), all of which were identified in IBC with a similar prevalence as in nIBC, except for the luminal A subtype (19% vs. 42%; P<0.001) and the HER2-enriched subtype (22% vs. 9%; P<0.001). Supervised analysis identified and validated an IBC-specific, molecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGF-β signaling in IBC. We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGF-β signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner. ©2013 AACR.

  6. Bulk and integrated acousto-optic spectrometers for molecular astronomy with heterodyne spectrometers

    NASA Technical Reports Server (NTRS)

    Chin, G.; Buhl, D.; Florez, J. M.

    1981-01-01

    A survey of acousto-optic spectrometers for molecular astronomy is presented, noting a technique of combining the acoustic bending of a collimated coherent light beam with a Bragg cell followed by an array of sensitive photodetectors. This acousto-optic spectrometer has a large bandwidth, a large number of channels, high resolution, and is energy efficient. Receiver development has concentrated on high-frequency heterodyne systems for the study of the chemical composition of the interstellar medium. RF spectrometers employing acousto-optic diffraction cells are described. Acousto-optic techniques have been suggested for applications to electronic warfare, electronic countermeasures and electronic support systems. Plans to use integrated optics for the further miniaturization of acousto-optic spectrometers are described. Bulk acousto-optic spectrometers with 300 MHz and 1 GHz bandwidths are being developed for use in the back-end of high-frequency heterodyne receivers for astronomical research.

  7. Theoretical Counseling Orientation: An Initial Aspect of Professional Orientation and Identity

    ERIC Educational Resources Information Center

    Jackson, James Lloyd, Jr.

    2010-01-01

    The literature on counselor development suggests that the development of a professional identity is a fundamental aspect of counselor training. The unique demands placed on counselors to integrate aspects of both personal and professional identity into the therapeutic process (Skovholt & Ronnestad, 1995) make development of a professional…

  8. Ranking product aspects through sentiment analysis of online reviews

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Wang, Hongwei; Song, Yuan

    2017-03-01

    The electronic word-of-mouth (e-WOM) is one of the most important among all the factors affecting consumers' behaviours. Opinions towards a product through online reviews will influence purchase decisions of other online consumers by changing their perceptions on the product quality. Furthermore, each product aspect may impact consumers' intentions differently. Thus, sentiment analysis and econometric models are incorporated to examine the relationship between purchase intentions and aspect-opinion pairs, which enable the weight estimation for each product aspect. We first identify product aspects and reduce dimensions to extract aspect-opinion pairs. Next the information gain is calculated for each aspect through entropy theory. Based on sentiment polarity and sentiment strength, we formulate an econometric model by integrating the information gain to measure the aspect's weight. In the experiment, we track 386 digital cameras on Amazon for 39 months, and results show that the aspect weight for digital cameras is detected more precisely than TF-ID and HAC algorithms. The results will bridge product aspects and consumption intention to facilitate e-WOM-based marketing.

  9. [Molecular techniques in mycology].

    PubMed

    Rodríguez-Tudela, Juan Luis; Cuesta, Isabel; Gómez-López, Alicia; Alastruey-Izquierdo, Ana; Bernal-Martínez, Leticia; Cuenca-Estrella, Manuel

    2008-11-01

    An increasing number of molecular techniques for the diagnosis of fungal infections have been developed in the last few years, due to the growing prevalence of mycoses and the length of time required for diagnosis when classical microbiological methods are used. These methods are designed to resolve the following aspects of mycological diagnosis: a) Identification of fungi to species level by means of sequencing relevant taxonomic targets; b) early clinical diagnosis of invasive fungal infections; c) detection of molecular mechanisms of resistance to antifungal agents; and d) molecular typing of fungi. Currently, these methods are restricted to highly developed laboratories. However, some of these techniques will probably be available in daily clinical practice in the near future.

  10. Communication: Phase diagram of C36 by atomistic molecular dynamics and thermodynamic integration through coexistence regions

    NASA Astrophysics Data System (ADS)

    Abramo, M. C.; Caccamo, C.; Costa, D.; Munaò, G.

    2014-09-01

    We report an atomistic molecular dynamics determination of the phase diagram of a rigid-cage model of C36. We first show that free energies obtained via thermodynamic integrations along isotherms displaying "van der Waals loops," are fully reproduced by those obtained via isothermal-isochoric integration encompassing only stable states. We find that a similar result also holds for isochoric paths crossing van der Waals regions of the isotherms, and for integrations extending to rather high densities where liquid-solid coexistence can be expected to occur. On such a basis we are able to map the whole phase diagram of C36, with resulting triple point and critical temperatures about 1770 K and 2370 K, respectively. We thus predict a 600 K window of existence of a stable liquid phase. Also, at the triple point density, we find that the structural functions and the diffusion coefficient maintain a liquid-like character down to 1400-1300 K, this indicating a wide region of possible supercooling. We discuss why all these features might render possible the observation of the melting of C36 fullerite and of its liquid state, at variance with what previously experienced for C60.

  11. Responses of plant seedlings to hypergravity: cellular and molecular aspects

    NASA Astrophysics Data System (ADS)

    Hoson, T.; Yoshioka, R.; Soga, K.; Wakabayashi, K.; Takeba, G.

    Hypergravity produced by centrifugation has been used to analyze the responses of plant seedlings to gravity stimulus. Elongation growth of stem organs is suppressed by hypergravity, which can be recognized as a way for plants to resist gravitational force. The mechanisms inducing growth suppression under hypergravity conditions were analyzed at cellular and molecular levels. When growth was suppressed by hypergravity, a decrease in the cell wall extensibility was brought about in various plants. Hypergravity also induced a cell wall thickening and an increase in the molecular mass of the certain hemicellulosic polysaccharides. Both a decrease in the activities hydrolyzing such polysaccharides and an increase in the apoplast pH were involved in such changes in the cell wall constituents. Thus, the cell wall metabolism is greatly modified under hypergravity conditions, which causes a decrease in the cell wall extensibility, thereby inhibiting elongation growth in stem organs. On the other hand, to identify genes involved in hypergravity-induced growth suppression, changes in gene expression by hypergravity treatment were analyzed in Arabidopsis hypocotyls by differential display method. Sixty-two genes were expressed differentially: expression levels of 39 genes increased, whereas those of 23 genes decreased under hypergravity conditions. The expression of these genes was further analyzed using RT-PCR. One of genes upregulated by hypergravity encoded hydroxymethylglutaryl-CoA reductase (HMGR), which catalyzes a reaction producing mevalonic acid, a key precursor of hormones such as gibberellic acid and abscisic acid. The expression of HMGR gene increased within several hours after hypergravity treatment. Also, compactin, an inhibitor of HMGR activity, prevented hypergravity-induced growth suppression, suggesting that HMGR is involved in suppression of Arabidopsis hypocotyl growth by hypergravity. In addition, hypergravity increased the expression levels of CCR1 and

  12. Integrating Sustainable Development into Operations Management Courses

    ERIC Educational Resources Information Center

    Fredriksson, Peter; Persson, Magnus

    2011-01-01

    Purpose: It is widely acknowledged that aspects of sustainable development (SD) should be integrated into higher level operations management (OM) education. The aim of the paper is to outline the experiences gained at Chalmers University of Technology in Sweden from integrating aspects of SD into OM courses. Design/methodology/approach: The paper…

  13. Integrated systems analysis reveals a molecular network underlying autism spectrum disorders

    PubMed Central

    Li, Jingjing; Shi, Minyi; Ma, Zhihai; Zhao, Shuchun; Euskirchen, Ghia; Ziskin, Jennifer; Urban, Alexander; Hallmayer, Joachim; Snyder, Michael

    2014-01-01

    Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA-sequencing of the corpus callosum from patients with autism exhibited extensive gene mis-expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology. PMID:25549968

  14. KINETIC AND DYNAMIC ASPECTS OF ARSENIC TOXICITY

    EPA Science Inventory

    This project integrates research on aspects of the kinetic and dynamic behavior of arsenic. A PBPK model for arsenic will be developed using metabolism and disposition data from studies in mice. Retention of arsenic in the tissues following exposure to arsenic will be investigate...

  15. Molecular dynamics approach to probe PKCβII-ligand interactions and influence of crystal water molecules on these interactions.

    PubMed

    Grewal, Baljinder K; Bhat, Jyotsna; Sobhia, Masilamani Elizabeth

    2015-01-01

    PKCβII is a potential target for therapeutic intervention against pandemic diabetic complications. Present study probes the molecular interactions of PKCβII with its clinically important ligands, viz. ruboxistaurin, enzastaurin and co-crystallized ligand, 2-methyl-1H-indol-3-yl-BIM-1. The essentials of PKCβII-ligand interaction, crystal water-induced alterations in these interactions and key interacting flexible residues are analyzed. Computational methodologies, viz. molecular docking and molecular simulation coupled with molecular mechanics-Poisson-Boltzmann surface area and generalized born surface area (MM-PB[GB]SA) are employed. The structural changes in the presence and absence of crystal water molecules in PKCβII ATP binding site residues, and its interaction with bound ligand, are identified. Difference in interaction of selective and nonselective ligand with ATP binding site residues of PKCβII is reported. The study showed that the nonbonding interactions contribute significantly in PKCβII-ligand binding and presence of crystal water molecules affects the interactions. The findings of present work may integrate the new aspects in the drug design process of PKCβII inhibitors.

  16. Integrating Nanostructured Artificial Receptors with Whispering Gallery Mode Optical Microresonators via Inorganic Molecular Imprinting Techniques

    PubMed Central

    Hammond, G. Denise; Vojta, Adam L.; Grant, Sheila A.; Hunt, Heather K.

    2016-01-01

    The creation of label-free biosensors capable of accurately detecting trace contaminants, particularly small organic molecules, is of significant interest for applications in environmental monitoring. This is achieved by pairing a high-sensitivity signal transducer with a biorecognition element that imparts selectivity towards the compound of interest. However, many environmental pollutants do not have corresponding biorecognition elements. Fortunately, biomimetic chemistries, such as molecular imprinting, allow for the design of artificial receptors with very high selectivity for the target. Here, we perform a proof-of-concept study to show how artificial receptors may be created from inorganic silanes using the molecular imprinting technique and paired with high-sensitivity transducers without loss of device performance. Silica microsphere Whispering Gallery Mode optical microresonators are coated with a silica thin film templated by a small fluorescent dye, fluorescein isothiocyanate, which serves as our model target. Oxygen plasma degradation and solvent extraction of the template are compared. Extracted optical devices are interacted with the template molecule to confirm successful sorption of the template. Surface characterization is accomplished via fluorescence and optical microscopy, ellipsometry, optical profilometry, and contact angle measurements. The quality factors of the devices are measured to evaluate the impact of the coating on device sensitivity. The resulting devices show uniform surface coating with no microstructural damage with Q factors above 106. This is the first report demonstrating the integration of these devices with molecular imprinting techniques, and could lead to new routes to biosensor creation for environmental monitoring. PMID:27314397

  17. Magnetic particles for in vitro molecular diagnosis: From sample preparation to integration into microsystems.

    PubMed

    Tangchaikeeree, Tienrat; Polpanich, Duangporn; Elaissari, Abdelhamid; Jangpatarapongsa, Kulachart

    2017-10-01

    Colloidal magnetic particles (MPs) have been developed in association with molecular diagnosis for several decades. MPs have the great advantage of easy manipulation using a magnet. In nucleic acid detection, these particles can act as a capture support for rapid and simple biomolecule separation. The surfaces of MPs can be modified by coating with various polymer materials to provide functionalization for different applications. The use of MPs enhances the sensitivity and specificity of detection due to the specific activity on the surface of the particles. Practical applications of MPs demonstrate greater efficiency than conventional methods. Beyond traditional detection, MPs have been successfully adopted as a smart carrier in microfluidic and lab-on-a-chip biosensors. The versatility of MPs has enabled their integration into small single detection units. MPs-based biosensors can facilitate rapid and highly sensitive detection of very small amounts of a sample. In this review, the application of MPs to the detection of nucleic acids, from sample preparation to analytical readout systems, is described. State-of-the-art integrated microsystems containing microfluidic and lab-on-a-chip biosensors for the nucleic acid detection are also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Outbreak Control and Clinical, Pathological, and Epidemiological Aspects and Molecular Characterization of a Bovine Herpesvirus Type 5 on a Feedlot Farm in São Paulo State

    PubMed Central

    Ferreira Vicente, Acácia; Appolinario, Camila Michele; Allendorf, Susan Dora; Gasparini Baraldi, Thaís; Cortez, Adriana; Bryan Heinemann, Marcos; Reinaldo Silva Fonseca, Clovis; Cristina Pelícia, Vanessa; Devidé Ribeiro, Bruna Leticia; Hiromi Okuda, Liria; Pituco, Edviges Maristela

    2015-01-01

    This paper describes the control, epidemiological, pathological, and molecular aspects of an outbreak of meningoencephalitis in calves due to bovine herpesvirus 5 at a feedlot with 540 animals in São Paulo State, Brazil. The introduction of new animals and contact between the resident animals and the introduced ones were most likely responsible for virus transmission. Bovine herpesvirus 1 vaccine was used, resulting in the efficacy of the outbreak control, although two bovine herpesvirus 1 positive animals, vaccinated and revaccinated, presented meningoencephalitis, thereby characterizing vaccinal failure. PMID:26090469

  19. Interface design for CMOS-integrated Electrochemical Impedance Spectroscopy (EIS) biosensors.

    PubMed

    Manickam, Arun; Johnson, Christopher Andrew; Kavusi, Sam; Hassibi, Arjang

    2012-10-29

    Electrochemical Impedance Spectroscopy (EIS) is a powerful electrochemical technique to detect biomolecules. EIS has the potential of carrying out label-free and real-time detection, and in addition, can be easily implemented using electronic integrated circuits (ICs) that are built through standard semiconductor fabrication processes. This paper focuses on the various design and optimization aspects of EIS ICs, particularly the bio-to-semiconductor interface design. We discuss, in detail, considerations such as the choice of the electrode surface in view of IC manufacturing, surface linkers, and development of optimal bio-molecular detection protocols. We also report experimental results, using both macro- and micro-electrodes to demonstrate the design trade-offs and ultimately validate our optimization procedures.

  20. Molecular similarity measures.

    PubMed

    Maggiora, Gerald M; Shanmugasundaram, Veerabahu

    2011-01-01

    Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

  1. Interventional Molecular Imaging.

    PubMed

    Solomon, Stephen B; Cornelis, Francois

    2016-04-01

    Although molecular imaging has had a dramatic impact on diagnostic imaging, it has only recently begun to be integrated into interventional procedures. Its significant impact is attributed to its ability to provide noninvasive, physiologic information that supplements conventional morphologic imaging. The four major interventional opportunities for molecular imaging are, first, to provide guidance to localize a target; second, to provide tissue analysis to confirm that the target has been reached; third, to provide in-room, posttherapy assessment; and fourth, to deliver targeted therapeutics. With improved understanding and application of(18)F-FDG, as well as the addition of new molecular probes beyond(18)F-FDG, the future holds significant promise for the expansion of molecular imaging into the realm of interventional procedures. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  2. Integrative molecular network analysis identifies emergent enzalutamide resistance mechanisms in prostate cancer

    PubMed Central

    King, Carly J.; Woodward, Josha; Schwartzman, Jacob; Coleman, Daniel J.; Lisac, Robert; Wang, Nicholas J.; Van Hook, Kathryn; Gao, Lina; Urrutia, Joshua; Dane, Mark A.; Heiser, Laura M.; Alumkal, Joshi J.

    2017-01-01

    Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines. Gene networks associated with enzalutamide resistance were revealed by performing an integrative genomic analysis with the PAthway Representation and Analysis by Direct Reference on Graphical Models (PARADIGM) tool. Amongst the pathways enriched in the enzalutamide-resistant cells were those associated with MEK, EGFR, RAS, and NFKB. Functional validation studies of 64 genes identified 10 candidate genes whose suppression led to greater effects on cell viability in enzalutamide-resistant cells as compared to sensitive parental cells. Examination of a patient cohort demonstrated that several of our functionally-validated gene hits are deregulated in metastatic CRPC tumor samples, suggesting that they may be clinically relevant therapeutic targets for patients with enzalutamide-resistant CRPC. Altogether, our approach demonstrates the potential of integrative genomic analyses to clarify determinants of drug resistance and rational co-targeting strategies to overcome resistance. PMID:29340039

  3. CPFP Summer Curriculum: Molecular Prevention Course | Division of Cancer Prevention

    Cancer.gov

    This Cancer Prevention Fellowship Program (CPFP) one-week course on molecular aspects of cancer prevention follows the Principles and Practice of Cancer Prevention and Control course. It provides a strong background about molecular biology and genetics of cancer, and an overview of cutting-edge research and techniques in the fields of molecular epidemiology, biomarkers,

  4. PosMed-plus: an intelligent search engine that inferentially integrates cross-species information resources for molecular breeding of plants.

    PubMed

    Makita, Yuko; Kobayashi, Norio; Mochizuki, Yoshiki; Yoshida, Yuko; Asano, Satomi; Heida, Naohiko; Deshpande, Mrinalini; Bhatia, Rinki; Matsushima, Akihiro; Ishii, Manabu; Kawaguchi, Shuji; Iida, Kei; Hanada, Kosuke; Kuromori, Takashi; Seki, Motoaki; Shinozaki, Kazuo; Toyoda, Tetsuro

    2009-07-01

    Molecular breeding of crops is an efficient way to upgrade plant functions useful to mankind. A key step is forward genetics or positional cloning to identify the genes that confer useful functions. In order to accelerate the whole research process, we have developed an integrated database system powered by an intelligent data-retrieval engine termed PosMed-plus (Positional Medline for plant upgrading science), allowing us to prioritize highly promising candidate genes in a given chromosomal interval(s) of Arabidopsis thaliana and rice, Oryza sativa. By inferentially integrating cross-species information resources including genomes, transcriptomes, proteomes, localizomes, phenomes and literature, the system compares a user's query, such as phenotypic or functional keywords, with the literature associated with the relevant genes located within the interval. By utilizing orthologous and paralogous correspondences, PosMed-plus efficiently integrates cross-species information to facilitate the ranking of rice candidate genes based on evidence from other model species such as Arabidopsis. PosMed-plus is a plant science version of the PosMed system widely used by mammalian researchers, and provides both a powerful integrative search function and a rich integrative display of the integrated databases. PosMed-plus is the first cross-species integrated database that inferentially prioritizes candidate genes for forward genetics approaches in plant science, and will be expanded for wider use in plant upgrading in many species.

  5. Multiple time step integrators in ab initio molecular dynamics.

    PubMed

    Luehr, Nathan; Markland, Thomas E; Martínez, Todd J

    2014-02-28

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

  6. 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.

  7. Integrative Learning: A Grounded Theory

    ERIC Educational Resources Information Center

    Leonard, Jeannie Brown

    2012-01-01

    This article reports the findings from a study of undergraduate students in an academic program focused on integrative learning rather than interdisciplinarity. One aspect of this study included how students defined integrative learning. This participant-shaped understanding of integrative learning was broad and reflected a continuum of…

  8. On virial analysis at low aspect ratio

    DOE PAGES

    Bongard, Michael W.; Barr, Jayson L.; Fonck, Raymond J.; ...

    2016-07-28

    The validity of virial analysis to infer global MHD equilibrium poloidal beta β p and internal inductance ℓ i from external magnetics measurements is examined for low aspect ratio configurations with A < 2. Numerical equilibrium studies at varied aspect ratio are utilized to validate the technique at finite aspect ratio. The effect of applying high-A approximations to low-A experimental data is quantified and demonstrates significant over-estimation of stored energy (factors of 2–10) in spherical tokamak geometry. Experimental approximations to equilibrium-dependent volume integral terms in the analysis are evaluated at low-A. Highly paramagnetic configurations are found to be inadequately representedmore » through the virial mean radius parameter R T. Alternate formulations for inferring β p and ℓ i that are independent of R T to avoid this difficulty are presented for the static isotropic limit. Lastly, these formulations are suitable for fast estimation of tokamak stored energy components at low aspect ratio using virial analysis.« less

  9. Path integral molecular dynamics for exact quantum statistics of multi-electronic-state systems.

    PubMed

    Liu, Xinzijian; Liu, Jian

    2018-03-14

    An exact approach to compute physical properties for general multi-electronic-state (MES) systems in thermal equilibrium is presented. The approach is extended from our recent progress on path integral molecular dynamics (PIMD), Liu et al. [J. Chem. Phys. 145, 024103 (2016)] and Zhang et al. [J. Chem. Phys. 147, 034109 (2017)], for quantum statistical mechanics when a single potential energy surface is involved. We first define an effective potential function that is numerically favorable for MES-PIMD and then derive corresponding estimators in MES-PIMD for evaluating various physical properties. Its application to several representative one-dimensional and multi-dimensional models demonstrates that MES-PIMD in principle offers a practical tool in either of the diabatic and adiabatic representations for studying exact quantum statistics of complex/large MES systems when the Born-Oppenheimer approximation, Condon approximation, and harmonic bath approximation are broken.

  10. Path integral molecular dynamics for exact quantum statistics of multi-electronic-state systems

    NASA Astrophysics Data System (ADS)

    Liu, Xinzijian; Liu, Jian

    2018-03-01

    An exact approach to compute physical properties for general multi-electronic-state (MES) systems in thermal equilibrium is presented. The approach is extended from our recent progress on path integral molecular dynamics (PIMD), Liu et al. [J. Chem. Phys. 145, 024103 (2016)] and Zhang et al. [J. Chem. Phys. 147, 034109 (2017)], for quantum statistical mechanics when a single potential energy surface is involved. We first define an effective potential function that is numerically favorable for MES-PIMD and then derive corresponding estimators in MES-PIMD for evaluating various physical properties. Its application to several representative one-dimensional and multi-dimensional models demonstrates that MES-PIMD in principle offers a practical tool in either of the diabatic and adiabatic representations for studying exact quantum statistics of complex/large MES systems when the Born-Oppenheimer approximation, Condon approximation, and harmonic bath approximation are broken.

  11. Six Years of Monitoring of the Sgr B2 Molecular Cloud with INTEGRAL

    NASA Astrophysics Data System (ADS)

    Terrier, R.; Bélanger, G.; Ponti, G.; Trap, G.; Goldwurm, A.; Decourchelle, A.

    2009-05-01

    Several molecular clouds around the Galactic Centre (GC) emit strong neutral iron fluorescence line at 6.4 keV, as well as hard X-ray emission up to 100 keV. The origin of this emission has long been a matter of controversy: irradiation by low energy cosmic ray electrons or X-rays emitted by a nearby flaring source in the central region. A recent evidence for time variability in the iron line intensity that has been detected in the Sgr B2 cloud favors the reflexion scenario. We present here the data obtained after 6 years of INTEGRAL monitoring of the GC. In particular, we show a lightcurve of Sgr B2 that reveals a decrease in the hard X-ray flux over the last years and discuss its implications. We finally discuss perspectives with Simbol-X.

  12. Molecular and Clinical Aspects of Protein Aggregation Assays in Neurodegenerative Diseases.

    PubMed

    Villar-Piqué, Anna; Schmitz, Matthias; Candelise, Niccolò; Ventura, Salvador; Llorens, Franc; Zerr, Inga

    2018-02-10

    The presence of protein deposits is a common pathological hallmark in patients suffering from neurodegenerative conditions and other proteinopathies. Deciphering the molecular basis of protein misfolding and aggregation is a crucial step towards the full comprehension of the factors that trigger the onset of these diseases and for the development of efficient therapeutical strategies. In this regard, in vitro aggregation assays for misfolded proteins offer an excellent tool to study pathological processes of protein deposition under controlled conditions, where confounders can be easily discriminated. These methods are generally cost-effective and have been proved useful in many fields, including drug discovery and clinical diagnostics. Here, we review the bases of in vitro aggregation and seeding assays, recapitulate their main applications and offer a critical evaluation of their limitations. Comprehending the molecular mechanisms behind these assays and combining them with in vivo or cell-based experiments will maximize their potential and allow the necessary improvement to overcome some of the current drawbacks.

  13. Molecular Aspects of Head and Neck Cancer Therapy

    PubMed Central

    Puram, Sidharth V.; Rocco, James W.

    2015-01-01

    Synopsis In spite of a rapidly expanding understanding of head and neck tumor biology as well as optimization of radiation, chemotherapy, and surgical treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer related morbidity and mortality. Although our biologic understanding of these tumors had largely been limited to pathways driving proliferation, survival, and differentiation, the identification of HPV as a major driver of HNSCC, specifically oropharyngeal SCC, as well as recent genomic sequencing analyses of HNSCC has dramatically influenced our understanding of the underlying biology behind carcinogenesis, and in part, our approach to therapy. In particular, we are at a major molecular and clinical crossroads with an explosion of promising diagnostic and therapeutic agents that hold great promise. Here, we summarize our current understanding of HNSCC biology, including a review of recent sequencing analyses, and identify promising areas for potential diagnostic and therapeutic agents. PMID:26568543

  14. Integrating pedagogical content knowledge and pedagogical/psychological knowledge in mathematics.

    PubMed

    Harr, Nora; Eichler, Andreas; Renkl, Alexander

    2014-01-01

    In teacher education at universities, general pedagogical and psychological principles are often treated separately from subject matter knowledge and therefore run the risk of not being applied in the teaching subject. In an experimental study (N = 60 mathematics student teachers) we investigated the effects of providing aspects of general pedagogical/psychological knowledge (PPK) and pedagogical content knowledge (PCK) in an integrated or separated way. In both conditions ("integrated" vs. "separated"), participants individually worked on computer-based learning environments addressing the same topic: use and handling of multiple external representations, a central issue in mathematics. We experimentally varied whether PPK aspects and PCK aspects were treated integrated or apart from one another. As expected, the integrated condition led to greater application of pedagogical/psychological aspects and an increase in applying both knowledge types simultaneously compared to the separated condition. Overall, our findings indicate beneficial effects of an integrated design in teacher education.

  15. Translational neurocardiology: preclinical models and cardioneural integrative aspects

    PubMed Central

    Andresen, M. C.; Armour, J. A.; Billman, G. E.; Chen, P.‐S.; Foreman, R. D.; Herring, N.; O'Leary, D. S.; Sabbah, H. N.; Schultz, H. D.; Sunagawa, K.; Zucker, I. H.

    2016-01-01

    Abstract Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various ‘levels’ become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. PMID:27098459

  16. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries.

    PubMed

    Santos, Raul D; Bourbon, Mafalda; Alonso, Rodrigo; Cuevas, Ada; Vasques-Cardenas, Norma Alexandra; Pereira, Alexandre C; Merchan, Alonso; Alves, Ana Catarina; Medeiros, Ana Margarida; Jannes, Cinthia E; Krieger, Jose E; Schreier, Laura; Perez de Isla, Leopoldo; Magaña-Torres, Maria Teresa; Stoll, Mario; Mata, Nelva; Dell Oca, Nicolas; Corral, Pablo; Asenjo, Sylvia; Bañares, Virginia G; Reyes, Ximena; Mata, Pedro

    There is little information about familial hypercholesterolemia (FH) epidemiology and care in Ibero-American countries. The Ibero-American FH network aims at reducing the gap on diagnosis and treatment of this disease in the region. To describe clinical, molecular, and organizational characteristics of FH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. Descriptive analysis of country data related to FH cascade screening, molecular diagnosis, clinical practice guidelines, and patient organization presence in Ibero-America. From a conservative estimation of an FH prevalence of 1 of 500 individuals, there should be 1.2 million heterozygous FH individuals in Ibero-America and roughly 27,400 were diagnosed so far. Only Spain, Brazil, Portugal, and Uruguay have active cascade screening programs. The prevalence of cardiovascular disease ranged from 10% to 42% in member countries, and the highest molecular identification rates are seen in Spain, 8.3%, followed by Portugal, 3.8%, and Uruguay with 2.5%. In the 3 countries with more FH patients identified (Spain, Portugal, and Brazil) between 10 and 15 mutations are responsible for 30% to 47% of all FH cases. Spain and Portugal share 5 of the 10 most common mutations (4 in low density lipoprotein receptor [LDLR] and the APOB3527). Spain and Spanish-speaking Latin American countries share 6 of the most common LDLR mutations and the APOB3527. LDL apheresis is available only in Spain and Portugal and not all countries have specific FH diagnostic and treatment guidelines as well as patient organizations. Ibero-American countries share similar mutations and gaps in FH care. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  17. Hybrid CMOS/Molecular Integrated Circuits

    NASA Astrophysics Data System (ADS)

    Stan, M. R.; Rose, G. S.; Ziegler, M. M.

    CMOS silicon technologies are likely to run out of steam in the next 10-15 years despite revolutionary advances in the past few decades. Molecular and other nanoscale technologies show significant promise but it is unlikely that they will completely replace CMOS, at least in the near term. This chapter explores opportunities for using CMOS and nanotechnology to enhance and complement each other in hybrid circuits. As an example of such a hybrid CMOS/nano system, a nanoscale programmable logic array (PLA) based on majority logic is described along with its supplemental CMOS circuitry. It is believed that such systems will be able to sustain the historical advances in the semiconductor industry while addressing manufacturability, yield, power, cost, and performance challenges.

  18. System integration case study : FAST-TRAC : preliminary IV deliverable : #2-systems integration case study

    DOT National Transportation Integrated Search

    1999-02-12

    This report focuses on the system integration aspect of the Transportation Information Management System (TIMS), a component of the FAST-TRAC project. The TIMS functions as the center of a communications network which integrates advanced traffic cont...

  19. Integrated Education in Contemporary Poland

    ERIC Educational Resources Information Center

    Apanel, Danuta

    2013-01-01

    This article presents the most important aspects, organizational principles and achievements in the field of integrated education in Poland. The author outlines the dynamics of the development of institutions of integrated education and institutions with integrated sections between 1989 and 2010. She describes the actual state of teaching…

  20. Molecular graph convolutions: moving beyond fingerprints

    NASA Astrophysics Data System (ADS)

    Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

    2016-08-01

    Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

  1. Molecular graph convolutions: moving beyond fingerprints.

    PubMed

    Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

    2016-08-01

    Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph-atoms, bonds, distances, etc.-which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

  2. The Center for Integrated Molecular Brain Imaging (Cimbi) database.

    PubMed

    Knudsen, Gitte M; Jensen, Peter S; Erritzoe, David; Baaré, William F C; Ettrup, Anders; Fisher, Patrick M; Gillings, Nic; Hansen, Hanne D; Hansen, Lars Kai; Hasselbalch, Steen G; Henningsson, Susanne; Herth, Matthias M; Holst, Klaus K; Iversen, Pernille; Kessing, Lars V; Macoveanu, Julian; Madsen, Kathrine Skak; Mortensen, Erik L; Nielsen, Finn Årup; Paulson, Olaf B; Siebner, Hartwig R; Stenbæk, Dea S; Svarer, Claus; Jernigan, Terry L; Strother, Stephen C; Frokjaer, Vibe G

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank. Copyright © 2015. Published by Elsevier Inc.

  3. Molecular digital pathology: progress and potential of exchanging molecular data.

    PubMed

    Roy, Somak; Pfeifer, John D; LaFramboise, William A; Pantanowitz, Liron

    2016-09-01

    Many of the demands to perform next generation sequencing (NGS) in the clinical laboratory can be resolved using the principles of telepathology. Molecular telepathology can allow facilities to outsource all or a portion of their NGS operation such as cloud computing, bioinformatics pipelines, variant data management, and knowledge curation. Clinical pathology laboratories can electronically share diverse types of molecular data with reference laboratories, technology service providers, and/or regulatory agencies. Exchange of electronic molecular data allows laboratories to perform validation of rare diseases using foreign data, check the accuracy of their test results against benchmarks, and leverage in silico proficiency testing. This review covers the emerging subject of molecular telepathology, describes clinical use cases for the appropriate exchange of molecular data, and highlights key issues such as data integrity, interoperable formats for massive genomic datasets, security, malpractice and emerging regulations involved with this novel practice.

  4. [Methodological aspects of integrated care pathways].

    PubMed

    Gomis, R; Mata Cases, M; Mauricio Puente, D; Artola Menéndez, S; Ena Muñoz, J; Mediavilla Bravo, J J; Miranda Fernández-Santos, C; Orozco Beltrán, D; Rodríguez Mañas, L; Sánchez Villalba, C; Martínez, J A

    An Integrated Healthcare Pathway (PAI) is a tool which has as its aim to increase the effectiveness of clinical performance through greater coordination and to ensure continuity of care. PAI places the patient as the central focus of the organisation of health services. It is defined as the set of activities carried out by the health care providers in order to increase the level of health and satisfaction of the population receiving services. The development of a PAI requires the analysis of the flow of activities, the inter-relationships between professionals and care teams, and patient expectations. The methodology for the development of a PAI is presented and discussed in this article, as well as the success factors for its definition and its effective implementation. It also explains, as an example, the recent PAI for Hypoglycaemia in patients with Type 2 Diabetes Mellitus developed by a multidisciplinary team and supported by several scientific societies. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Integration of alternative feedstreams for biomass treatment and utilization

    DOEpatents

    Hennessey, Susan Marie [Avondale, PA; Friend, Julie [Claymont, DE; Dunson, Jr., James B.; Tucker, III, Melvin P.; Elander, Richard T [Evergreen, CO; Hames, Bonnie [Westminster, CO

    2011-03-22

    The present invention provides a method for treating biomass composed of integrated feedstocks to produce fermentable sugars. One aspect of the methods described herein includes a pretreatment step wherein biomass is integrated with an alternative feedstream and the resulting integrated feedstock, at relatively high concentrations, is treated with a low concentration of ammonia relative to the dry weight of biomass. In another aspect, a high solids concentration of pretreated biomass is integrated with an alternative feedstream for saccharifiaction.

  6. Molecular Electronic Shift Registers

    NASA Technical Reports Server (NTRS)

    Beratan, David N.; Onuchic, Jose N.

    1990-01-01

    Molecular-scale shift registers eventually constructed as parts of high-density integrated memory circuits. In principle, variety of organic molecules makes possible large number of different configurations and modes of operation for such shift-register devices. Several classes of devices and implementations in some specific types of molecules proposed. All based on transfer of electrons or holes along chains of repeating molecular units.

  7. SOCIAL PSYCHOLOGICAL ASPECTS OF SCHOOL BUILDING DESIGN.

    ERIC Educational Resources Information Center

    KEITH, PAT M.; SMITH, LOUIS M.

    THE DEVELOPMENT AND INTEGRATION OF SOCIOPSYCHOLOGICAL ASPECTS OF SCHOOL DESIGN WERE INVESTIGATED BY FOCUSING ON THE IMPACT OF A UNIQUELY DESIGNED ELEMENTARY SCHOOL BUILDING, THE KENSINGTON SCHOOL. AN ATTEMPT WAS MADE TO SYNTHESIZE ROLE THEORY, DECISION MAKING THEORY, SOCIAL SYSTEM THEORY, AND SUCH PROBLEM AREAS AS STAFF PEER GROUPS, EDUCATIONAL…

  8. Education for All Aspects of the Industry.

    ERIC Educational Resources Information Center

    Bailey, Thomas; And Others

    1995-01-01

    Education for all aspects of the industry (AAI) is a strategy that is being advocated by education reformers to combine learning and experience, integrate vocational and academic education, develop more interdisciplinary instruction, and forge more links between schools, business, and the community. A study examined AAI from the perspective of the…

  9. EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

    NASA Astrophysics Data System (ADS)

    Weinelt, Martin; von Oppen, Felix

    2012-10-01

    In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on

  10. Translational neurocardiology: preclinical models and cardioneural integrative aspects.

    PubMed

    Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

    2016-07-15

    Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  11. Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer's Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data.

    PubMed

    Kocis, Petr; Tolar, Martin; Yu, Jeremy; Sinko, William; Ray, Soumya; Blennow, Kaj; Fillit, Howard; Hey, John A

    2017-06-01

    Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease. Therefore, to build on this important efficacy attribute and to further improve its pharmaceutical properties, we have developed a prodrug of tramiprosate ALZ-801 that is in advanced stages of clinical development. To elucidate how tramiprosate works, we investigated its molecular mechanism of action (MOA) and the translation to observed clinical outcomes. The two main objectives of this research were to (1) elucidate and characterize the MOA of tramiprosate via an integrated application of three independent molecular methodologies and (2) present an integrated translational analysis that links the MOA, conformation of the target, stoichiometry, and pharmacokinetic dose exposure to the observed clinical outcome in APOE4/4 homozygote subjects. We used three molecular analytical methods-ion mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR), and molecular dynamics-to characterize the concentration-related interactions of tramiprosate versus Aβ42 monomers and the resultant conformational alterations affecting aggregation into oligomers. The molecular stoichiometry of the tramiprosate versus Aβ42 interaction was further analyzed in the context of clinical pharmacokinetic dose exposure and central nervous system Aβ42 levels (i.e., pharmacokinetic-pharmacodynamic translation in humans). We observed a multi-ligand interaction of tramiprosate with monomeric Aβ42

  12. Molecular and clinical aspects of GHRH receptor mutations.

    PubMed

    Corazzini, Valentina; Salvatori, Roberto

    2013-01-01

    The growth hormone (GH)-releasing hormone (GHRH) receptor (GHRHR) belongs to the G protein-coupled receptor family. It binds GHRH resulting in somatotroph cell proliferation and stimulation of GH secretion. Mutations in the gene encoding for GHRHR (GHRHR, OMIM No. 139191) are being reported with increasing frequency in familial isolated GH deficiency. To date, the reported GHRHR mutations include eight missense, seven splice, three microdeletions, and two non-sense mutations. One promoter mutation has also been reported. Most of these mutations show a recessive mode of inheritance. The phenotype includes reduced but not absent serum GH, with abnormal response to a variety of stimuli, and low serum insulin-like growth factor-1 levels, resulting in proportionate growth failure which becomes evident in the first year of life. These patients respond well to GH replacement therapy. Phenotypical observations coming from some unusually large kindreds with untreated GH deficiency due to homozygous GHRHR mutations have allowed the study of the consequences of lifetime lack of GH. This chapter reviews the structure and the role of the GHRHR together with the clinical aspects associated with its mutations. Copyright © 2013 S. Karger AG, Basel.

  13. Food allergens: molecular and immunological aspects, allergen databases and cross-reactivity.

    PubMed

    Lorenz, Anne-Regine; Scheurer, Stephan; Vieths, Stefan

    2015-01-01

    The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome. © 2015 S. Karger AG, Basel.

  14. Integrating HIV testing and care into tuberculosis services in Benin: programmatic aspects.

    PubMed

    Ferroussier, O; Dlodlo, R A; Capo-Chichi, D; Boillot, F; Gninafon, M; Trébucq, A; Fujiwara, P I

    2013-11-01

    Between 2005 and 2008, the diagnosis and care of human immunodeficiency virus (HIV) infection and tuberculosis (TB) services were integrated in Benin. The appointment of a TB-HIV Coordinator by the National Tuberculosis Control Programme and quarterly supervisory visits to TB clinics have bolstered the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole preventive therapy were integrated smoothly into the TB services. The strategy chosen to facilitate access of HIV-positive TB patients to antiretroviral treatment contributed to greater integration over time, but perpetuated, for some, the burden of attending two facilities. The integration and decentralisation of TB and HIV care services at national level in Benin resulted in a high uptake of HIV services among TB patients.

  15. Chemistry integrated circuit: chemical system on a complementary metal oxide semiconductor integrated circuit.

    PubMed

    Nakazato, Kazuo

    2014-03-28

    By integrating chemical reactions on a large-scale integration (LSI) chip, new types of device can be created. For biomedical applications, monolithically integrated sensor arrays for potentiometric, amperometric and impedimetric sensing of biomolecules have been developed. The potentiometric sensor array detects pH and redox reaction as a statistical distribution of fluctuations in time and space. For the amperometric sensor array, a microelectrode structure for measuring multiple currents at high speed has been proposed. The impedimetric sensor array is designed to measure impedance up to 10 MHz. The multimodal sensor array will enable synthetic analysis and make it possible to standardize biosensor chips. Another approach is to create new functional devices by integrating molecular systems with LSI chips, for example image sensors that incorporate biological materials with a sensor array. The quantum yield of the photoelectric conversion of photosynthesis is 100%, which is extremely difficult to achieve by artificial means. In a recently developed process, a molecular wire is plugged directly into a biological photosynthetic system to efficiently conduct electrons to a gold electrode. A single photon can be detected at room temperature using such a system combined with a molecular single-electron transistor.

  16. Exploring Social Equity Aspects in Integrating Technology in Primary Mathematics Education

    ERIC Educational Resources Information Center

    Stoilescu, Dorian

    2014-01-01

    This research focus on aspects of equity related to the introduction of using technology in classrooms. Technology has the potential to support mathematics pedagogy with visual representations and offer modelling and simulation facilities, increasing the creativity of the learning and teaching processes (Kaput, Ness, & Hoyles, 2008; Stoilescu…

  17. Molecular dysexpression in gastric cancer revealed by integrated analysis of transcriptome data.

    PubMed

    Li, Xiaomei; Dong, Weiwei; Qu, Xueling; Zhao, Huixia; Wang, Shuo; Hao, Yixin; Li, Qiuwen; Zhu, Jianhua; Ye, Min; Xiao, Wenhua

    2017-05-01

    Gastric cancer (GC) is often diagnosed in the advanced stages and is associated with a poor prognosis. Obtaining an in depth understanding of the molecular mechanisms of GC has lagged behind compared with other cancers. This study aimed to identify candidate biomarkers for GC. An integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between GC and normal tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed to identify the functions of the DEGs. Furthermore, a protein-protein interaction (PPI) network of the DEGs was constructed. The expression levels of the DEGs were validated in human GC tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A set of 689 DEGs were identified in GC tissues, as compared with normal tissues, including 202 upregulated DEGs and 487 downregulated DEGs. The KEGG pathway analysis suggested that various pathways may play important roles in the pathology of GC, including pathways related to protein digestion and absorption, extracellular matrix-receptor interaction, and the metabolism of xenobiotics by cytochrome P450. The PPI network analysis indicated that the significant hub proteins consisted of SPP1, TOP2A and ARPC1B. RT-qPCR validation indicated that the expression levels of the top 10 most significantly dysexpressed genes were consistent with the illustration of the integrated analysis. The present study yielded a reference list of reliable DEGs, which represents a robust pool of candidates for further evaluation of GC pathogenesis and treatment.

  18. Differentiating snail intermediate hosts of Schistosoma spp. using molecular approaches: fundamental to successful integrated control mechanism in Africa.

    PubMed

    Abe, Eniola Michael; Guan, Wei; Guo, Yun-Hai; Kassegne, Kokouvi; Qin, Zhi-Qiang; Xu, Jing; Chen, Jun-Hu; Ekpo, Uwem Friday; Li, Shi-Zhu; Zhou, Xiao-Nong

    2018-03-26

    Snail intermediate hosts play active roles in the transmission of snail-borne trematode infections in Africa. A good knowledge of snail-borne diseases epidemiology particularly snail intermediate host populations would provide the necessary impetus to complementing existing control strategy. This review highlights the importance of molecular approaches in differentiating snail hosts population structure and the need to provide adequate information on snail host populations by updating snail hosts genome database for Africa, in order to equip different stakeholders with adequate information on the ecology of snail intermediate hosts and their roles in the transmission of different diseases. Also, we identify the gaps and areas where there is need for urgent intervention to facilitate effective integrated control of schistosomiasis and other snail-borne trematode infections. Prioritizing snail studies, especially snail differentiation using molecular tools will boost disease surveillance and also enhance efficient schistosomaisis control programme in Africa.

  19. Cellular and molecular mechanisms of HIV-1 integration targeting.

    PubMed

    Engelman, Alan N; Singh, Parmit K

    2018-07-01

    Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies. The integrase additionally senses target DNA distortion and nucleotide sequence to help fine-tune the specific phosphodiester bonds that are cleaved at integration sites. Research into virus-host interactions that underlie HIV-1 integration targeting has aided the development of a novel class of integrase inhibitors and may help to improve the safety of viral-based gene therapy vectors.

  20. Human Factors Engineering Aspects of Modifications in Control Room Modernization

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

    Hugo, Jacques; Clefton, Gordon; Joe, Jeffrey

    This report describes the basic aspects of control room modernization projects in the U.S. nuclear industry and the need for supplementary guidance on the integration of human factors considerations into the licensing and regulatory aspects of digital upgrades. The report pays specific attention to the integration of principles described in NUREG-0711 (Human Factors Engineering Program Review Model) and how supplementary guidance can help to raise general awareness in the industry regarding the complexities of control room modernization projects created by many interdependent regulations, standards and guidelines. The report also describes how human factors engineering principles and methods provided by variousmore » resources and international standards can help in navigating through the process of licensing digital upgrades. In particular, the integration of human factors engineering guidance and requirements into the process of licensing digital upgrades can help reduce uncertainty related to development of technical bases for digital upgrades that will avoid the introduction of new failure modes.« less

  1. 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

  2. Biophysical Aspects of T Lymphocyte Activation at the Immune Synapse

    PubMed Central

    Hivroz, Claire; Saitakis, Michael

    2016-01-01

    T lymphocyte activation is a pivotal step of the adaptive immune response. It requires the recognition by T-cell receptors (TCR) of peptides presented in the context of major histocompatibility complex molecules (pMHC) present at the surface of antigen-presenting cells (APCs). T lymphocyte activation also involves engagement of costimulatory receptors and adhesion molecules recognizing ligands on the APC. Integration of these different signals requires the formation of a specialized dynamic structure: the immune synapse. While the biochemical and molecular aspects of this cell–cell communication have been extensively studied, its mechanical features have only recently been addressed. Yet, the immune synapse is also the place of exchange of mechanical signals. Receptors engaged on the T lymphocyte surface are submitted to many tensile and traction forces. These forces are generated by various phenomena: membrane undulation/protrusion/retraction, cell mobility or spreading, and dynamic remodeling of the actomyosin cytoskeleton inside the T lymphocyte. Moreover, the TCR can both induce force development, following triggering, and sense and convert forces into biochemical signals, as a bona fide mechanotransducer. Other costimulatory molecules, such as LFA-1, engaged during immune synapse formation, also display these features. Moreover, T lymphocytes themselves are mechanosensitive, since substrate stiffness can modulate their response. In this review, we will summarize recent studies from a biophysical perspective to explain how mechanical cues can affect T lymphocyte activation. We will particularly discuss how forces are generated during immune synapse formation; how these forces affect various aspects of T lymphocyte biology; and what are the key features of T lymphocyte response to stiffness. PMID:26913033

  3. [Sport as a profession: medical and social aspects].

    PubMed

    Izmerov, N F

    2011-01-01

    The author analyses possible use of methods and achievements of industrial medicine in solving problems of acme in sports. The article covers theoretic, methodologic and practical basis for possible integration of industrial medicine and sports medicine. Mechanisms of such interdisciplinary integration include current legal basis, scientific research (mostly, concept of occupational risk, norm and pathology concept, doctrine of preventive medicine, etc), practical experience accumulated in this country and abroad. Some aspects of public health preservation in contemporary Russia are also tackled.

  4. A Pipeline To Enhance Ligand Virtual Screening: Integrating Molecular Dynamics and Fingerprints for Ligand and Proteins.

    PubMed

    Spyrakis, Francesca; Benedetti, Paolo; Decherchi, Sergio; Rocchia, Walter; Cavalli, Andrea; Alcaro, Stefano; Ortuso, Francesco; Baroni, Massimo; Cruciani, Gabriele

    2015-10-26

    The importance of taking into account protein flexibility in drug design and virtual ligand screening (VS) has been widely debated in the literature, and molecular dynamics (MD) has been recognized as one of the most powerful tools for investigating intrinsic protein dynamics. Nevertheless, deciphering the amount of information hidden in MD simulations and recognizing a significant minimal set of states to be used in virtual screening experiments can be quite complicated. Here we present an integrated MD-FLAP (molecular dynamics-fingerprints for ligand and proteins) approach, comprising a pipeline of molecular dynamics, clustering and linear discriminant analysis, for enhancing accuracy and efficacy in VS campaigns. We first extracted a limited number of representative structures from tens of nanoseconds of MD trajectories by means of the k-medoids clustering algorithm as implemented in the BiKi Life Science Suite ( http://www.bikitech.com [accessed July 21, 2015]). Then, instead of applying arbitrary selection criteria, that is, RMSD, pharmacophore properties, or enrichment performances, we allowed the linear discriminant analysis algorithm implemented in FLAP ( http://www.moldiscovery.com [accessed July 21, 2015]) to automatically choose the best performing conformational states among medoids and X-ray structures. Retrospective virtual screenings confirmed that ensemble receptor protocols outperform single rigid receptor approaches, proved that computationally generated conformations comprise the same quantity/quality of information included in X-ray structures, and pointed to the MD-FLAP approach as a valuable tool for improving VS performances.

  5. Novel aspects of plasma control in ITER

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

    Humphreys, D.; Jackson, G.; Walker, M.

    2015-02-15

    ITER plasma control design solutions and performance requirements are strongly driven by its nuclear mission, aggressive commissioning constraints, and limited number of operational discharges. In addition, high plasma energy content, heat fluxes, neutron fluxes, and very long pulse operation place novel demands on control performance in many areas ranging from plasma boundary and divertor regulation to plasma kinetics and stability control. Both commissioning and experimental operations schedules provide limited time for tuning of control algorithms relative to operating devices. Although many aspects of the control solutions required by ITER have been well-demonstrated in present devices and even designed satisfactorily formore » ITER application, many elements unique to ITER including various crucial integration issues are presently under development. We describe selected novel aspects of plasma control in ITER, identifying unique parts of the control problem and highlighting some key areas of research remaining. Novel control areas described include control physics understanding (e.g., current profile regulation, tearing mode (TM) suppression), control mathematics (e.g., algorithmic and simulation approaches to high confidence robust performance), and integration solutions (e.g., methods for management of highly subscribed control resources). We identify unique aspects of the ITER TM suppression scheme, which will pulse gyrotrons to drive current within a magnetic island, and turn the drive off following suppression in order to minimize use of auxiliary power and maximize fusion gain. The potential role of active current profile control and approaches to design in ITER are discussed. Issues and approaches to fault handling algorithms are described, along with novel aspects of actuator sharing in ITER.« less

  6. Novel aspects of plasma control in ITER

    DOE PAGES

    Humphreys, David; Ambrosino, G.; de Vries, Peter; ...

    2015-02-12

    ITER plasma control design solutions and performance requirements are strongly driven by its nuclear mission, aggressive commissioning constraints, and limited number of operational discharges. In addition, high plasma energy content, heat fluxes, neutron fluxes, and very long pulse operation place novel demands on control performance in many areas ranging from plasma boundary and divertor regulation to plasma kinetics and stability control. Both commissioning and experimental operations schedules provide limited time for tuning of control algorithms relative to operating devices. Although many aspects of the control solutions required by ITER have been well-demonstrated in present devices and even designed satisfactorily formore » ITER application, many elements unique to ITER including various crucial integration issues are presently under development. We describe selected novel aspects of plasma control in ITER, identifying unique parts of the control problem and highlighting some key areas of research remaining. Novel control areas described include control physics understanding (e.g. current profile regulation, tearing mode suppression (TM)), control mathematics (e.g. algorithmic and simulation approaches to high confidence robust performance), and integration solutions (e.g. methods for management of highly-subscribed control resources). We identify unique aspects of the ITER TM suppression scheme, which will pulse gyrotrons to drive current within a magnetic island, and turn the drive off following suppression in order to minimize use of auxiliary power and maximize fusion gain. The potential role of active current profile control and approaches to design in ITER are discussed. Finally, issues and approaches to fault handling algorithms are described, along with novel aspects of actuator sharing in ITER.« less

  7. Molecular graph convolutions: moving beyond fingerprints

    PubMed Central

    Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

    2016-01-01

    Molecular “fingerprints” encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement. PMID:27558503

  8. Discovering Socio-cultural Aspects of Science Through Artworks

    NASA Astrophysics Data System (ADS)

    Güney, Burcu Gülay; Şeker, Hayati

    2017-11-01

    Scientific literacy is one of the primary purposes of science education which briefly focuses on using and interpreting scientific explanations, understanding science within its culture. However, science curricula emphasize science with its cognitive aspects and underestimate affective and aesthetic aspects of science. Science education needs to cover beauty of science for students to cross borders between their own culture and culture of science and to achieve the aim of scientific literacy. Relating aesthetic aspects of science with content of science and paving the way for aesthetic experiences through artworks may enrich science education. The purposes of this study are to discuss the need of integrating aesthetic aspects of science in science instruction and to propose examples and pedagogical suggestions to promote aesthetic experiences into the science education. Artworks are selected to present socio-cultural aspects of science to demonstrate the culture of science, their stories are explained, and pedagogical suggestions are proposed. Advantages and difficulties of using artworks in science instruction are discussed as a result of the study.

  9. Molecular aspects of ultraviolet radiation-induced apoptosis in the skin.

    PubMed

    Chow, Jeffrey; Tron, Victor A

    2005-12-01

    Apoptosis, or programmed cell death, is an essential physiological process that controls cell numbers during physiological processes, and eliminates abnormal cells that can potentially harm an organism. This review summarizes our current state of knowledge of apoptosis induction in skin by UV radiation. A review of the literature was undertaken focusing on cell death in the skin secondary to UV radiation. It is evident that a number of apoptotic pathways, both intrinsic and extrinsic, are induced following exposure to damaging UV radiation. Although our understanding of the apoptotic processes is gradually increasing, many important aspects remain obscure. These include interconnections between pathways, wavelength-specific differences and cell type differences.

  10. From Gene to Structure: "Lactobacillus Bulgaricus" D-Lactate Dehydrogenase from Yogurt as an Integrated Curriculum Model for Undergraduate Molecular Biology and Biochemistry Laboratory Courses

    ERIC Educational Resources Information Center

    Lawton, Jeffrey A.; Prescott, Noelle A.; Lawton, Ping X.

    2018-01-01

    We have developed an integrated, project-oriented curriculum for undergraduate molecular biology and biochemistry laboratory courses spanning two semesters that is organized around the "ldhA" gene from the yogurt-fermenting bacterium "Lactobacillus bulgaricus," which encodes the enzyme d-lactate dehydrogenase. The molecular…

  11. Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene

    PubMed Central

    Astolfi, Annalisa; Patterson, Janice; Nannini, Margherita; Saponara, Maristella; Gatto, Lidia; Santini, Donatella; do Valle, Italo F.; Castellani, Gastone; Fiorentino, Michelangelo; von Mehren, Margaret; Brandi, Giovanni; Biasco, Guido; Heinrich, Michael C.; Pantaleo, Maria Abbondanza

    2018-01-01

    Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha (PDGFRA) gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein–ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course. We found a very specific gene expression profile of D842V mutant tumors showing the activation of G-protein-coupled receptor (GPCR) signaling and a relative downregulation of cell cycle processes. Beyond D842V, no recurrently mutated genes were found in our cohort. Nevertheless, many private, clinically relevant alterations were found in each tumor (TP53, IDH1, FBXW7, SDH-complex). Molecular modeling of PDGFRA D842V suggests that the mutant protein binds imatinib with lower affinity with respect to wild-type structure, showing higher stability during the interaction with other type I TKIs (like crenolanib). D842V mutant GIST do not show any actionable recurrent molecular events of therapeutic significance, therefore this study supports the rationale of novel TKIs development that are currently being evaluated in clinical studies for the treatment of D842V mutant GIST. PMID:29510530

  12. Agrobacterium-assisted selenium nanoparticles: molecular aspect of antifungal activity

    NASA Astrophysics Data System (ADS)

    Kumar, Anil; Bera, Smritilekha; Singh, Man; Mondal, Dhananjoy

    2018-03-01

    Selenium nanoparticles (SeNPs) were synthesized through the bioreduction of sodium selenite (Na2SeO3) using gram-negative agrobacterium (AGBT) species. Subsequently, their physicochemical properties (pH, viscosity and surface tension) and medicinal activities as anti-dermatophyte against soil keratinophilic fungi at the molecular level were assessed. UV-visible and FTIR spectroscopic data of the biologically synthesized SeNPs were then recorded for confirming the presence of native biological materials adhered to nanoparticles, which are inherently required to enhance the stability and solubility through inhibition of the nanoparticle’s natural aggregation and agglomeration. The λ max value between 290-300 nm in the absorption spectra of the biogenic materials in different concentrations of the Na2SeO3 corroborated the presence of SeNPs in the solution. The interaction of SeNPs in solution state was further studied through the determination of pH, viscosity and surface tension values of agrobacterium-derived SeNPs in different solvents. The pH value of SeNPs dispersed in water is reported as above 7.0 and the average viscosity, and surface tensions of the SeNPs are appeared as near to the water. The particle size distribution was further determined by DLS and the highest % of particle size of the synthesized SeNPs is found in between 200-300 nm. The anti-dermatophyte activity and molecular interaction with fungi DNA molecules were assessed providing the highest anti-dermatophyte activity at 0.1 M concentration and it is observed that the quantities and qualities of fungi DNA were affected by SeNPs. Considering all the outcomes of the studies together, our findings suggest that agrobacterium-mediated synthesis of SeNPs is dependent on bacterial metabolisms but not on the concentration of Na2SeO3 and are promising selenium-derived species with potential application in the prevention of fungal infection through denaturation of fungi DNA.

  13. Molecular Strategies for Morphology Control in Semiconducting Polymers for Optoelectronics.

    PubMed

    Rahmanudin, Aiman; Sivula, Kevin

    2017-06-28

    Solution-processable semiconducting polymers have been explored over the last decades for their potential applications in inexpensively fabricated transistors, diodes and photovoltaic cells. However, a remaining challenge in the field is to control the solid-state self-assembly of polymer chains in thin films devices, as the aspects of (semi)crystallinity, grain boundaries, and chain entanglement can drastically affect intra-and inter-molecular charge transport/transfer and thus device performance. In this short review we examine how the aspects of molecular weight and chain rigidity affect solid-state self-assembly and highlight molecular engineering strategies to tune thin film morphology. Side chain engineering, flexibly linking conjugation segments, and block co-polymer strategies are specifically discussed with respect to their effect on field effect charge carrier mobility in transistors and power conversion efficiency in solar cells. Example systems are taken from recent literature including work from our laboratories to illustrate the potential of molecular engineering semiconducting polymers.

  14. Assessing the potential of surface-immobilized molecular logic machines for integration with solid state technology.

    PubMed

    Dunn, Katherine E; Trefzer, Martin A; Johnson, Steven; Tyrrell, Andy M

    2016-08-01

    Molecular computation with DNA has great potential for low power, highly parallel information processing in a biological or biochemical context. However, significant challenges remain for the field of DNA computation. New technology is needed to allow multiplexed label-free readout and to enable regulation of molecular state without addition of new DNA strands. These capabilities could be provided by hybrid bioelectronic systems in which biomolecular computing is integrated with conventional electronics through immobilization of DNA machines on the surface of electronic circuitry. Here we present a quantitative experimental analysis of a surface-immobilized OR gate made from DNA and driven by strand displacement. The purpose of our work is to examine the performance of a simple representative surface-immobilized DNA logic machine, to provide valuable information for future work on hybrid bioelectronic systems involving DNA devices. We used a quartz crystal microbalance to examine a DNA monolayer containing approximately 5×10(11)gatescm(-2), with an inter-gate separation of approximately 14nm, and we found that the ensemble of gates took approximately 6min to switch. The gates could be switched repeatedly, but the switching efficiency was significantly degraded on the second and subsequent cycles when the binding site for the input was near to the surface. Otherwise, the switching efficiency could be 80% or better, and the power dissipated by the ensemble of gates during switching was approximately 0.1nWcm(-2), which is orders of magnitude less than the power dissipated during switching of an equivalent array of transistors. We propose an architecture for hybrid DNA-electronic systems in which information can be stored and processed, either in series or in parallel, by a combination of molecular machines and conventional electronics. In this architecture, information can flow freely and in both directions between the solution-phase and the underlying electronics

  15. Integrated Marketing in Higher Education. Research Report 01-01.

    ERIC Educational Resources Information Center

    Morris, L. Michelle; Cejda, Brent D.

    Integrated marketing deals with aspects often referred to as the "4 Ps": product, price, place, and promotion. These aspects have also been described as the "4 Cs": customer, cost, convenience, and communication. Integrated marketing has been defined as "a listening-first, database-dependent approach to marketing that includes both a willingness…

  16. What makes protein indigestible from tissue-related, cellular, and molecular aspects?

    PubMed

    Becker, Petra M; Yu, Peiqiang

    2013-10-01

    This paper gives an insight into key factors, which impair enzymatic protein digestion. By nature, some proteins in raw products are already poorly digestible because of structural peculiarities, or due to their occurrence in plant cytoplasmic organelles or in cell membranes. In plant-based protein, molecular and structural changes can be induced by genetic engineering, even if protein is not a target compound class of the genetic modification. Other proteins only become difficult to digest due to changes that occur during the processing of proteinaceous products, such as extruding, boiling, or acidic or alkaline treatment. The utilization of proteinaceous raw materials in industrial fermentations can also have negative impacts on protein digestibility, when reused as fermentation by-products for animal nutrition, such as brewers' grains. After consumption, protein digestion can be impeded in the intestine by the presence of antinutritional factors, which are ingested together with the food or feedstuff. It is concluded that the encircling matrix, but also molecular, chemical, and structural peculiarities or modifications to amino acids and proteins obstruct protein digestion by common proteolytic enzymes in humans and animals. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. The (FHCl)- molecular anion - Structural aspects, global surface, and vibrational eigenspectrum

    NASA Technical Reports Server (NTRS)

    Klepeis, Neil E.; East, Allan L. L.; Csaszar, Attila G.; Allen, Wesley D.; Lee, Timothy J.; Schwenke, David W.

    1993-01-01

    State of the art ab initio electronic structure methods have been used to investigate the (FHCl)- molecular anion. It is proposed that the geometric structure and binding energies of the complex are r(e)(H-F) = 0.963 +/- 0.003 A, R(e)(H-Cl) = 1.925 +/- 0.015 A, and D0(HF + Cl(-)) = 21.8 +/- 0.4 kcal/mol. A Morokuma decomposition of the ion-molecular bonding give the following electrostatic, polarization, exchange repulsion, dispersion, and charge-transfer plus higher-order mixing components of the vibrationless complexation energy: -27.3, -5.2, +18.3, -4.5, and -5.0 kcal/mol, respectively. A couples cluster single and doubles global surface is constructed from 208 and 228 energy points for linear and bent configurations, respectively, these being fit to rms errors of only 3.9 and 9.3/cm, respectively, below 8000/cm. Converged J = 0 and J = 1 variational eigenstates of the (FHCl)- surface to near the HF + Cl(-) dissociation threshold are determined. The fundamental vibrational frequencies are found to be nu1 = 247/cm, nu2 = 876/cm, and nu3 = 2884/cm. The complete vibrational eigenspectrum is analyzed.

  18. Molecular chirality: language, history, and significance.

    PubMed

    Gal, Joseph

    2013-01-01

    In this chapter some background material concerning molecular chirality and enantiomerism is presented. First some basic chemical-molecular aspects of chirality are reviewed, after which certain relevant terminology whose use in the literature has been problematic is discussed. Then an overview is provided of some of the early discoveries that laid the foundations of the science of molecular chirality in chemistry and biology, including the discovery of the phenomenon of molecular chirality by L. Pasteur, the proposals for the asymmetric carbon atom by J.H. van 't Hoff and J.A. Lebel, Pasteur's discovery of biological enantioselectivity, the discovery of enantioselectivity at biological receptors by A. Piutti, the studies of enzymatic stereoselectivity by E. Fischer, and the work on enantioselectivity in pharmacology by A. Cushny. Finally, the role of molecular chirality in pharmacotherapy and new-drug development, arguably one of the main driving forces for the current intense interest in the phenomenon of molecular chirality, is discussed.

  19. Digital Aquifer - Integrating modeling, technical, software and policy aspects to develop a groundwater management tool

    NASA Astrophysics Data System (ADS)

    Tirupathi, S.; McKenna, S. A.; Fleming, K.; Wambua, M.; Waweru, P.; Ondula, E.

    2016-12-01

    Groundwater management has traditionally been observed as a study for long term policy measures to ensure that the water resource is sustainable. IBM Research, in association with the World Bank, extended this traditional analysis to include realtime groundwater management by building a context-aware, water rights management and permitting system. As part of this effort, one of the primary objectives was to develop a groundwater flow model that can help the policy makers with a visual overview of the current groundwater distribution. In addition, the system helps the policy makers simulate a range of scenarios and check the sustainability of the groundwater resource in a given region. The system also enables a license provider to check the effect of the introduction of a new well on the existing wells in the domain as well as the groundwater resource in general. This process simplifies how an engineer will determine if a new well should be approved. Distance to the nearest well neighbors and the maximum decreases in water levels of nearby wells are continually assessed and presented as evidence for an engineer to make the final judgment on approving the permit. The system also facilitates updated insights on the amount of groundwater left in an area and provides advice on how water fees should be structured to balance conservation and economic development goals. In this talk, we will discuss the concept of Digital Aquifer, the challenges in integrating modeling, technical and software aspects to develop a management system that helps policy makers and license providers with a robust decision making tool. We will concentrate on the groundwater model developed using the analytic element method that plays a very important role in the decision making aspects. Finally, the efficiency of this system and methodology is shown through a case study in Laguna Province, Philippines, which was done in collaboration with the National Water Resource Board, Philippines and World

  20. Exploring molecular networks using MONET ontology.

    PubMed

    Silva, João Paulo Müller da; Lemke, Ney; Mombach, José Carlos; Souza, José Guilherme Camargo de; Sinigaglia, Marialva; Vieira, Renata

    2006-03-31

    The description of the complex molecular network responsible for cell behavior requires new tools to integrate large quantities of experimental data in the design of biological information systems. These tools could be used in the characterization of these networks and in the formulation of relevant biological hypotheses. The building of an ontology is a crucial step because it integrates in a coherent framework the concepts necessary to accomplish such a task. We present MONET (molecular network), an extensible ontology and an architecture designed to facilitate the integration of data originating from different public databases in a single- and well-documented relational database, that is compatible with MONET formal definition. We also present an example of an application that can easily be implemented using these tools.

  1. In vivo assessment of aortic aneurysm wall integrity using elastin-specific molecular magnetic resonance imaging.

    PubMed

    Botnar, René M; Wiethoff, Andrea J; Ebersberger, Ullrich; Lacerda, Sara; Blume, Ulrike; Warley, Alice; Jansen, Christian H P; Onthank, David C; Cesati, Richard R; Razavi, Reza; Marber, Michael S; Hamm, Bernd; Schaeffter, Tobias; Robinson, Simon P; Makowski, Marcus R

    2014-07-01

    The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs. © 2014 American Heart Association, Inc.

  2. Direct monolithic integration of vertical single crystalline octahedral molecular sieve nanowires on silicon

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

    Carretero-Genevrier, Adrian; Oro-Sole, Judith; Gazquez, Jaume

    2013-12-13

    We developed an original strategy to produce vertical epitaxial single crystalline manganese oxide octahedral molecular sieve (OMS) nanowires with tunable pore sizes and compositions on silicon substrates by using a chemical solution deposition approach. The nanowire growth mechanism involves the use of track-etched nanoporous polymer templates combined with the controlled growth of quartz thin films at the silicon surface, which allowed OMS nanowires to stabilize and crystallize. α-quartz thin films were obtained after thermal activated crystallization of the native amorphous silica surface layer assisted by Sr 2+- or Ba 2+-mediated heterogeneous catalysis in the air at 800 °C. These α-quartzmore » thin films work as a selective template for the epitaxial growth of randomly oriented vertical OMS nanowires. Furthermore, the combination of soft chemistry and epitaxial growth opens new opportunities for the effective integration of novel technological functional tunneled complex oxides nanomaterials on Si substrates.« less

  3. Laser-enhanced dynamics in molecular rate processes

    NASA Technical Reports Server (NTRS)

    George, T. F.; Zimmerman, I. H.; Devries, P. L.; Yuan, J.-M.; Lam, K.-S.; Bellum, J. C.; Lee, H.-W.; Slutsky, M. S.

    1978-01-01

    The present discussion deals with some theoretical aspects associated with the description of molecular rate processes in the presence of intense laser radiation, where the radiation actually interacts with the molecular dynamics. Whereas for weak and even moderately intense radiation, the absorption and stimulated emission of photons by a molecular system can be described by perturbative methods, for intense radiation, perturbation theory is usually not adequate. Limiting the analysis to the gas phase, an attempt is made to describe nonperturbative approaches applicable to the description of such processes (in the presence of intense laser radiation) as electronic energy transfer in molecular (in particular atom-atom) collisions; collision-induced ionization and emission; and unimolecular dissociation.

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

    PubMed

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

    2016-06-17

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

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

    PubMed Central

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

    2016-01-01

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

  6. A hybrid approach to survival model building using integration of clinical and molecular information in censored data.

    PubMed

    Choi, Ickwon; Kattan, Michael W; Wells, Brian J; Yu, Changhong

    2012-01-01

    In medical society, the prognostic models, which use clinicopathologic features and predict prognosis after a certain treatment, have been externally validated and used in practice. In recent years, most research has focused on high dimensional genomic data and small sample sizes. Since clinically similar but molecularly heterogeneous tumors may produce different clinical outcomes, the combination of clinical and genomic information, which may be complementary, is crucial to improve the quality of prognostic predictions. However, there is a lack of an integrating scheme for clinic-genomic models due to the P ≥ N problem, in particular, for a parsimonious model. We propose a methodology to build a reduced yet accurate integrative model using a hybrid approach based on the Cox regression model, which uses several dimension reduction techniques, L₂ penalized maximum likelihood estimation (PMLE), and resampling methods to tackle the problem. The predictive accuracy of the modeling approach is assessed by several metrics via an independent and thorough scheme to compare competing methods. In breast cancer data studies on a metastasis and death event, we show that the proposed methodology can improve prediction accuracy and build a final model with a hybrid signature that is parsimonious when integrating both types of variables.

  7. Integrating pedagogical content knowledge and pedagogical/psychological knowledge in mathematics

    PubMed Central

    Harr, Nora; Eichler, Andreas; Renkl, Alexander

    2014-01-01

    In teacher education at universities, general pedagogical and psychological principles are often treated separately from subject matter knowledge and therefore run the risk of not being applied in the teaching subject. In an experimental study (N = 60 mathematics student teachers) we investigated the effects of providing aspects of general pedagogical/psychological knowledge (PPK) and pedagogical content knowledge (PCK) in an integrated or separated way. In both conditions (“integrated” vs. “separated”), participants individually worked on computer-based learning environments addressing the same topic: use and handling of multiple external representations, a central issue in mathematics. We experimentally varied whether PPK aspects and PCK aspects were treated integrated or apart from one another. As expected, the integrated condition led to greater application of pedagogical/psychological aspects and an increase in applying both knowledge types simultaneously compared to the separated condition. Overall, our findings indicate beneficial effects of an integrated design in teacher education. PMID:25191300

  8. Integrals for IBS and beam cooling

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

    Burov, A.; /Fermilab

    Simulation of beam cooling usually requires performing certain integral transformations every time step or so, which is a significant burden on the CPU. Examples are the dispersion integrals (Hilbert transforms) in the stochastic cooling, wake fields and IBS integrals. An original method is suggested for fast and sufficiently accurate computation of the integrals. This method is applied for the dispersion integral. Some methodical aspects of the IBS analysis are discussed.

  9. Integrals for IBS and Beam Cooling

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

    Burov, A.

    Simulation of beam cooling usually requires performing certain integral transformations every time step or so, which is a significant burden on the CPU. Examples are the dispersion integrals (Hilbert transforms) in the stochastic cooling, wake fields and IBS integrals. An original method is suggested for fast and sufficiently accurate computation of the integrals. This method is applied for the dispersion integral. Some methodical aspects of the IBS analysis are discussed.

  10. Constituent Aspects of Workplace Guidance in Secondary VET

    ERIC Educational Resources Information Center

    Swager, Robert; Klarus, Ruud; van Merriënboer, Jeroen J. G.; Nieuwenhuis, Loek F. M.

    2015-01-01

    Purpose: This paper aims to present an integrated model of workplace guidance to enhance awareness of what constitutes good guidance, to improve workplace guidance practices in vocational education and training. Design/methodology/approach: To identify constituent aspects of workplace guidance, a systematic search of Web of Science was conducted,…

  11. A microfluidic system with integrated molecular imprinting polymer films for surface plasmon resonance detection

    NASA Astrophysics Data System (ADS)

    Huang, Shih-Chiang; Lee, Gwo-Bin; Chien, Fan-Ching; Chen, Shean-Jen; Chen, Wen-Janq; Yang, Ming-Chang

    2006-07-01

    This paper presents a novel microfluidic system with integrated molecular imprinting polymer (MIP) films designed for surface plasmon resonance (SPR) biosensing of multiple nanoscale biomolecules. The innovative microfluidic chip uses pneumatic microvalves and micropumps to transport a precise amount of the biosample through multiple microchannels to sensing regions containing the locally spin-coated MIP films. The signals of SPR biosensing are basically proportional to the number of molecules adsorbed on the MIP films. Hence, a precise control of flow rates inside microchannels is important to determine the adsorption amount of the molecules in the SPR/MIP chips. The integration of micropumps and microvalves can automate the sample introduction process and precisely control the amount of the sample injection to the microfluidic system. The proposed biochip enables the label-free biosensing of biomolecules in an automatic format, and provides a highly sensitive, highly specific and high-throughput detection performance. Three samples, i.e. progesterone, cholesterol and testosterone, are successfully detected using the developed system. The experimental results show that the proposed SPR/MIP microfluidic chip provides a comparable sensitivity to that of large-scale SPR techniques, but with reduced sample consumption and an automatic format. As such, the developed biochip has significant potential for a wide variety of nanoscale biosensing applications. The preliminary results of the current paper were presented at Transducers 2005, Seoul, Korea, 5-9 June 2005.

  12. Application of computer-assisted molecular modeling (CAMM) for immunoassay of low molecular weight food contaminants: A review

    USDA-ARS?s Scientific Manuscript database

    Immunoassay for low molecular weight food contaminants, such as pesticides, veterinary drugs, and mycotoxins is now a well-established technique which meets the demands for a rapid, reliable, and cost-effective analytical method. However, due to limited understanding of the fundamental aspects of i...

  13. Strategic, Organizational and Standardization Aspects of Integrated Information Systems. Volume 6.

    DTIC Science & Technology

    1987-12-01

    TEST CHART NATIONAL BUREAU OF STANDARDS- 1963-A Masaustt Strategic, Organizational, and Intueoyffomto TechnlogyStandardization Aspects of UJ Kowledge ...reasons (such as the desired level of processing power and the amount of storage space), organizational reasons (such as each department obtaining its...of processing power falls, Abbott can afford to subordinate efficient processing for organizational effectiveness. 4. Steps in an Analytical Process

  14. Practical aspects of protein co-evolution.

    PubMed

    Ochoa, David; Pazos, Florencio

    2014-01-01

    Co-evolution is a fundamental aspect of Evolutionary Theory. At the molecular level, co-evolutionary linkages between protein families have been used as indicators of protein interactions and functional relationships from long ago. Due to the complexity of the problem and the amount of genomic data required for these approaches to achieve good performances, it took a relatively long time from the appearance of the first ideas and concepts to the quotidian application of these approaches and their incorporation to the standard toolboxes of bioinformaticians and molecular biologists. Today, these methodologies are mature (both in terms of performance and usability/implementation), and the genomic information that feeds them large enough to allow their general application. This review tries to summarize the current landscape of co-evolution-based methodologies, with a strong emphasis on describing interesting cases where their application to important biological systems, alone or in combination with other computational and experimental approaches, allowed getting new insight into these.

  15. Practical aspects of protein co-evolution

    PubMed Central

    Ochoa, David; Pazos, Florencio

    2014-01-01

    Co-evolution is a fundamental aspect of Evolutionary Theory. At the molecular level, co-evolutionary linkages between protein families have been used as indicators of protein interactions and functional relationships from long ago. Due to the complexity of the problem and the amount of genomic data required for these approaches to achieve good performances, it took a relatively long time from the appearance of the first ideas and concepts to the quotidian application of these approaches and their incorporation to the standard toolboxes of bioinformaticians and molecular biologists. Today, these methodologies are mature (both in terms of performance and usability/implementation), and the genomic information that feeds them large enough to allow their general application. This review tries to summarize the current landscape of co-evolution-based methodologies, with a strong emphasis on describing interesting cases where their application to important biological systems, alone or in combination with other computational and experimental approaches, allowed getting new insight into these. PMID:25364721

  16. Chemical Modification of Semiconductor Surfaces for Molecular Electronics.

    PubMed

    Vilan, Ayelet; Cahen, David

    2017-03-08

    Inserting molecular monolayers within metal/semiconductor interfaces provides one of the most powerful expressions of how minute chemical modifications can affect electronic devices. This topic also has direct importance for technology as it can help improve the efficiency of a variety of electronic devices such as solar cells, LEDs, sensors, and possible future bioelectronic ones. The review covers the main aspects of using chemistry to control the various aspects of interface electrostatics, such as passivation of interface states and alignment of energy levels by intrinsic molecular polarization, as well as charge rearrangement with the adjacent metal and semiconducting contacts. One of the greatest merits of molecular monolayers is their capability to form excellent thin dielectrics, yielding rich and unique current-voltage characteristics for transport across metal/molecular monolayer/semiconductor interfaces. We explain the interplay between the monolayer as tunneling barrier on the one hand, and the electrostatic barrier within the semiconductor, due to its space-charge region, on the other hand, as well as how different monolayer chemistries control each of these barriers. Practical tools to experimentally identify these two barriers and distinguish between them are given, followed by a short look to the future. This review is accompanied by another one, concerning the formation of large-area molecular junctions and charge transport that is dominated solely by molecules.

  17. Teaching psychosocial aspects of coronary care.

    PubMed

    Egnew, T R; Jones, J M

    1984-01-01

    For the past two years, Tacoma Family Medicine, Tacoma, Washington. has integrated a curriculum in psychosocial aspects of coronary care with the Coronary Care Unit rotation taken by third-year residents. Goals of the curriculum are to provide information, to foster the development of psychosocial strategies for patient and family care, and to develop greater insight and awareness on the part of residents regarding the psychosocial aspects of coronary care. Attempts are made to meet these goals in a context as closely tied to the clinical management of patients and families as possible. Topics addressed include the biopsychosocial medical model, patient and family responses to cardiac illness, sexual concerns of the coronary patient and spouse, and issues related to cardiac rehabilitation. The format for the curriculum involves didactic presentations, group discussions, and case consultations.

  18. A collaborative molecular modeling environment using a virtual tunneling service.

    PubMed

    Lee, Jun; Kim, Jee-In; Kang, Lin-Woo

    2012-01-01

    Collaborative researches of three-dimensional molecular modeling can be limited by different time zones and locations. A networked virtual environment can be utilized to overcome the problem caused by the temporal and spatial differences. However, traditional approaches did not sufficiently consider integration of different computing environments, which were characterized by types of applications, roles of users, and so on. We propose a collaborative molecular modeling environment to integrate different molecule modeling systems using a virtual tunneling service. We integrated Co-Coot, which is a collaborative crystallographic object-oriented toolkit, with VRMMS, which is a virtual reality molecular modeling system, through a collaborative tunneling system. The proposed system showed reliable quantitative and qualitative results through pilot experiments.

  19. A Collaborative Molecular Modeling Environment Using a Virtual Tunneling Service

    PubMed Central

    Lee, Jun; Kim, Jee-In; Kang, Lin-Woo

    2012-01-01

    Collaborative researches of three-dimensional molecular modeling can be limited by different time zones and locations. A networked virtual environment can be utilized to overcome the problem caused by the temporal and spatial differences. However, traditional approaches did not sufficiently consider integration of different computing environments, which were characterized by types of applications, roles of users, and so on. We propose a collaborative molecular modeling environment to integrate different molecule modeling systems using a virtual tunneling service. We integrated Co-Coot, which is a collaborative crystallographic object-oriented toolkit, with VRMMS, which is a virtual reality molecular modeling system, through a collaborative tunneling system. The proposed system showed reliable quantitative and qualitative results through pilot experiments. PMID:22927721

  20. Progress in the molecular diagnosis of Lyme disease.

    PubMed

    Ružić-Sabljić, Eva; Cerar, Tjaša

    2017-01-01

    Current laboratory testing of Lyme borreliosis mostly relies on serological methods with known limitations. Diagnostic modalities enabling direct detection of pathogen at the onset of the clinical signs could overcome some of the limitations. Molecular methods detecting borrelial DNA seem to be the ideal solution, although there are some aspects that need to be considered. Areas covered: This review represent summary and discussion of the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) together with our own experience on molecular diagnosis of Lyme disease. Expert commentary: Molecular methods are promising and currently serve as supporting diagnostic testing in Lyme borreliosis. Since the field of molecular diagnostics is under rapid development, molecular testing could become an important diagnostic modality.

  1. [Molecular imaging; current status and future prospects in USA].

    PubMed

    Kobayashi, Hisataka

    2007-02-01

    The goal of this review is to introduce the definition, current status, and future prospects of the molecular imaging, which has recently been a hot topic in medicine and the biological science in USA. In vivo imaging methods to visualize the molecular events and functions in organs or animals/humans are overviewed and discussed especially in combinations of imaging modalities (machines) and contrast agents(chemicals) used in the molecular imaging. Next, the close relationship between the molecular imaging and the nanotechnology, an important part of nanomedicine, is stressed from the aspect of united multidisciplinary sciences such as physics, chemistry, biology, and medicine.

  2. Genetically identified spinal interneurons integrating tactile afferents for motor control

    PubMed Central

    Panek, Izabela; Farah, Carl

    2015-01-01

    Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing. PMID:26445867

  3. Aspect-Oriented Model-Driven Software Product Line Engineering

    NASA Astrophysics Data System (ADS)

    Groher, Iris; Voelter, Markus

    Software product line engineering aims to reduce development time, effort, cost, and complexity by taking advantage of the commonality within a portfolio of similar products. The effectiveness of a software product line approach directly depends on how well feature variability within the portfolio is implemented and managed throughout the development lifecycle, from early analysis through maintenance and evolution. This article presents an approach that facilitates variability implementation, management, and tracing by integrating model-driven and aspect-oriented software development. Features are separated in models and composed of aspect-oriented composition techniques on model level. Model transformations support the transition from problem to solution space models. Aspect-oriented techniques enable the explicit expression and modularization of variability on model, template, and code level. The presented concepts are illustrated with a case study of a home automation system.

  4. Integrating molecular diagnostic and flow cytometric reporting for improved longitudinal monitoring of HIV patients.

    PubMed Central

    Asare, A. L.; Huda, H.; Klimczak, J. C.; Caldwell, C. W.

    1998-01-01

    Studies have shown that monitoring HIV-infected patients undergoing antiretroviral therapy is best represented by combined measurement of plasma HIV-1 RNA and CD4+ T-lymphocytes [1]. This pilot study at the University of Missouri-Columbia integrates molecular diagnostic and flow cytometric data reporting to provide current and historical HIV-1 RNA levels and CD4+ T-cell counts. The development of a single database for storage and retrieval of these values facilitates composite report generation that includes longitudinal HIV-1 RNA levels and CD4+ T-cell counts for all patients. Results are displayed in tables and plotted graphically within a web browser. This method of data presentation converts individual data points to more useful medical information and could provide clinicians with decision support for improved monitoring of HIV patients undergoing antiretroviral therapy. Images Figure 2 Figure 3 Figure 4 PMID:9929359

  5. Molecular and Biotechnological Aspects of Microbial Proteases†

    PubMed Central

    Rao, Mala B.; Tanksale, Aparna M.; Ghatge, Mohini S.; Deshpande, Vasanti V.

    1998-01-01

    diverse origins have been analyzed with the aim of studying their evolutionary relationships. Despite the extensive research on several aspects of proteases, there is a paucity of knowledge about the roles that govern the diverse specificity of these enzymes. Deciphering these secrets would enable us to exploit proteases for their applications in biotechnology. PMID:9729602

  6. The molecular electronic device and the biochip computer: present status.

    PubMed

    Haddon, R C; Lamola, A A

    1985-04-01

    The idea that a single molecule might function as a self-contained electronic device has been of interest for some time. However, a fully integrated version--the biochip or the biocomputer, in which both production and assembly of molecular electronic components is achieved through biotechnology-is a relatively new concept that is currently attracting attention both within the scientific community and among the general public. In the present article we draw together some of the approaches being considered for the construction of such devices and delineate the revolutionary nature of the current proposals for molecular electronic devices (MEDs) and biochip computers (BCCs). With the silicon semiconductor conductor industry already in place and in view of the continuing successes of the lithographic process it seems appropriate to ask why the highly speculative MED or BCC has engendered such interest. In some respects the answer is paradigmatic as much as it is real. It is perhaps best stated as the promise of the realm of the molecular. Thus it is envisioned that devices will be constructed by assembly of individual molecular electronic components into arrays, thereby engineering from small upward rather than large downward as do current lithographic techniques. An important corollary of the construction technique is that the functional elements of such an array would be individual molecules rather than macroscopic ensembles. These two aspects of the MED/BCC--assembly of molecular arrays and individually accessible functional molecular units--are truly revolutionary. Both require scientific breakthroughs and the necessary principles, quite apart from the technology, remain essentially unknown. It is concluded that the advent of the MED/BCC still lies well before us. The twin criteria of utilization of individual molecules as functional elements and the assembly of such elements remains as elusive as ever. Biology engineers structures on the molecular scale but

  7. The molecular electronic device and the biochip computer: present status.

    PubMed Central

    Haddon, R C; Lamola, A A

    1985-01-01

    The idea that a single molecule might function as a self-contained electronic device has been of interest for some time. However, a fully integrated version--the biochip or the biocomputer, in which both production and assembly of molecular electronic components is achieved through biotechnology-is a relatively new concept that is currently attracting attention both within the scientific community and among the general public. In the present article we draw together some of the approaches being considered for the construction of such devices and delineate the revolutionary nature of the current proposals for molecular electronic devices (MEDs) and biochip computers (BCCs). With the silicon semiconductor conductor industry already in place and in view of the continuing successes of the lithographic process it seems appropriate to ask why the highly speculative MED or BCC has engendered such interest. In some respects the answer is paradigmatic as much as it is real. It is perhaps best stated as the promise of the realm of the molecular. Thus it is envisioned that devices will be constructed by assembly of individual molecular electronic components into arrays, thereby engineering from small upward rather than large downward as do current lithographic techniques. An important corollary of the construction technique is that the functional elements of such an array would be individual molecules rather than macroscopic ensembles. These two aspects of the MED/BCC--assembly of molecular arrays and individually accessible functional molecular units--are truly revolutionary. Both require scientific breakthroughs and the necessary principles, quite apart from the technology, remain essentially unknown. It is concluded that the advent of the MED/BCC still lies well before us. The twin criteria of utilization of individual molecules as functional elements and the assembly of such elements remains as elusive as ever. Biology engineers structures on the molecular scale but

  8. Intelligent multi-sensor integrations

    NASA Technical Reports Server (NTRS)

    Volz, Richard A.; Jain, Ramesh; Weymouth, Terry

    1989-01-01

    Growth in the intelligence of space systems requires the use and integration of data from multiple sensors. Generic tools are being developed for extracting and integrating information obtained from multiple sources. The full spectrum is addressed for issues ranging from data acquisition, to characterization of sensor data, to adaptive systems for utilizing the data. In particular, there are three major aspects to the project, multisensor processing, an adaptive approach to object recognition, and distributed sensor system integration.

  9. Photon Upconversion and Molecular Solar Energy Storage by Maximizing the Potential of Molecular Self-Assembly.

    PubMed

    Kimizuka, Nobuo; Yanai, Nobuhiro; Morikawa, Masa-Aki

    2016-11-29

    The self-assembly of functional molecules into ordered molecular assemblies and the fulfillment of potentials unique to their nanotomesoscopic structures have been one of the central challenges in chemistry. This Feature Article provides an overview of recent progress in the field of molecular self-assembly with the focus on the triplet-triplet annihilation-based photon upconversion (TTA-UC) and supramolecular storage of photon energy. On the basis of the integration of molecular self-assembly and photon energy harvesting, triplet energy migration-based TTA-UC has been achieved in varied molecular systems. Interestingly, some molecular self-assemblies dispersed in solution or organogels revealed oxygen barrier properties, which allowed TTA-UC even under aerated conditions. The elements of molecular self-assembly were also introduced to the field of molecular solar thermal fuel, where reversible photoliquefaction of ionic crystals to ionic liquids was found to double the molecular storage capacity with the simultaneous pursuit of switching ionic conductivity. A future prospect in terms of innovating molecular self-assembly toward molecular systems chemistry is also discussed.

  10. Molecular imaging of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Chang, Sung K.; Errabelli, Divya; Rizvi, Imran; Solban, Nicolas; O'Riordan, Katherine; Hasan, Tayyaba

    2006-02-01

    Recent advances in light sources, detectors and other optical imaging technologies coupled with the development of novel optical contrast agents have enabled real-time, high resolution, in vivo monitoring of molecular targets. Noninvasive monitoring of molecular targets is particularly relevant to photodynamic therapy (PDT), including the delivery of photosensitizer in the treatment site and monitoring of molecular and physiological changes following treatment. Our lab has developed optical imaging technologies to investigate these various aspects of photodynamic therapy (PDT). We used a laser scanning confocal microscope to monitor the pharmacokinetics of various photosensitizers in in vitro as well as ex vivo samples, and developed an intravital fluorescence microscope to monitor photosensitizer delivery in vivo in small animals. A molecular specific contrast agent that targets the vascular endothelial growth factor (VEGF) was developed to monitor the changes in the protein expression following PDT. We were then able to study the physiological changes due to post-treatment VEGF upregulation by quantifying vascular permeability with in vivo imaging.

  11. Integration of the stratigraphic aspects of very large sea-floor databases using information processing

    USGS Publications Warehouse

    Jenkins, Clinton N.; Flocks, J.; Kulp, M.; ,

    2006-01-01

    Information-processing methods are described that integrate the stratigraphic aspects of large and diverse collections of sea-floor sample data. They efficiently convert common types of sea-floor data into database and GIS (geographical information system) tables, visual core logs, stratigraphic fence diagrams and sophisticated stratigraphic statistics. The input data are held in structured documents, essentially written core logs that are particularly efficient to create from raw input datasets. Techniques are described that permit efficient construction of regional databases consisting of hundreds of cores. The sedimentological observations in each core are located by their downhole depths (metres below sea floor - mbsf) and also by a verbal term that describes the sample 'situation' - a special fraction of the sediment or position in the core. The main processing creates a separate output event for each instance of top, bottom and situation, assigning top-base mbsf values from numeric or, where possible, from word-based relative locational information such as 'core catcher' in reference to sampler device, and recovery or penetration length. The processing outputs represent the sub-bottom as a sparse matrix of over 20 sediment properties of interest, such as grain size, porosity and colour. They can be plotted in a range of core-log programs including an in-built facility that better suits the requirements of sea-floor data. Finally, a suite of stratigraphic statistics are computed, including volumetric grades, overburdens, thicknesses and degrees of layering. ?? The Geological Society of London 2006.

  12. RICOR's new development of a highly reliable integral rotary cooler: engineering and reliability aspects

    NASA Astrophysics Data System (ADS)

    Filis, Avishai; Pundak, Nachman; Barak, Moshe; Porat, Ze'ev; Jaeger, Mordechai

    2011-06-01

    The growing demand for EO applications that work around the clock 24hr/7days a week, such as in border surveillance systems, emphasizes the need for a highly reliable cryocooler having increased operational availability and decreased integrated system Life Cycle (ILS) cost. In order to meet this need RICOR has developed a new rotary Stirling cryocooler, model K508N, intended to double the K508's operating MTTF achieving 20,000 operating MTTF hours. The K508N employs RICOR's latest mechanical design technologies such as optimized bearings and greases, bearings preloading, advanced seals, laser welded cold finger and robust design structure with increased natural frequency compared to the K508 model. The cooler enhanced MTTF was demonstrated by a Validation and Verification (V&V) plan comprising analytical means and a comparative accelerated life test between the standard K508 and the K508N models. Particularly, point estimate and confidence interval for the MTTF improvement factor where calculated periodically during and after the test. The (V&V) effort revealed that the K508N meets its MTTF design goal. The paper will focus on the technical and engineering aspects of the new design. In addition it will discuss the market needs and expectations, investigate the reliability data of the present reference K508 model; and report the accelerate life test data and the statistical analysis methodology as well as its underlying assumptions and results.

  13. Integration for Severely Handicapped Children and Youth.

    ERIC Educational Resources Information Center

    Stremel-Campbell, Kathleen

    1983-01-01

    A model for integrating severely handicapped children and youth is composed of five major components: (1) general integration (in which a needs assessment determines such aspects as visibility of the classroom, interaction with regular classroom staff, and school-home communication); (2) active integration (in which educational and social…

  14. Integration of a zebrafish research project into a molecular biology course to support critical thinking and course content goals.

    PubMed

    Felzien, Lisa K

    2016-11-12

    Engaging undergraduates in research is essential for teaching them to think like scientists, and it has become a desired component of classroom and laboratory instruction. Research projects that span an entire semester expose students to a variety of concepts and techniques and allow students to use experiments to learn scientific principles, understand why specific techniques are applicable, critically analyze varied data, and examine how experimentation leads to acquiring knowledge. To provide an experience with these features, a semester long research project was integrated into a combined lecture and laboratory course, Molecular Biology. The project utilized the zebrafish model to examine gene expression during embryonic development and required students to develop and test hypotheses about the timing of expression of previously uncharacterized genes. The main goals for the project were to provide opportunities for students to develop critical thinking skills required for conducting research and to support the content goals of the course. To determine whether these goals were met, student performance on the steps of the project and related pre-test and post-test questions was examined. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):565-573, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

  15. Integrating classical and molecular approaches to evaluate the impact of nanosized zero-valent iron (nZVI) on soil organisms.

    PubMed

    Saccà, Maria Ludovica; Fajardo, Carmen; Costa, Gonzalo; Lobo, Carmen; Nande, Mar; Martin, Margarita

    2014-06-01

    Nanosized zero-valent iron (nZVI) is a new option for the remediation of contaminated soil and groundwater, but the effect of nZVI on soil biota is mostly unknown. In this work, nanotoxicological studies were performed in vitro and in two different standard soils to assess the effect of nZVI on autochthonous soil organisms by integrating classical and molecular analysis. Standardised ecotoxicity testing methods using Caenorhabditis elegans were applied in vitro and in soil experiments and changes in microbial biodiversity and biomarker gene expression were used to assess the responses of the microbial community to nZVI. The classical tests conducted in soil ruled out a toxic impact of nZVI on the soil nematode C. elegans in the test soils. The molecular analysis applied to soil microorganisms, however, revealed significant changes in the expression of the proposed biomarkers of exposure. These changes were related not only to the nZVI treatment but also to the soil characteristics, highlighting the importance of considering the soil matrix on a case by case basis. Furthermore, due to the temporal shift between transcriptional responses and the development of the corresponding phenotype, the molecular approach could anticipate adverse effects on environmental biota. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Influence of platelet aspect ratio on the mechanical behaviour of bio-inspired nanocomposites using molecular dynamics.

    PubMed

    Mathiazhagan, S; Anup, S

    2016-06-01

    Superior mechanical properties of biocomposites such as nacre and bone are attributed to their basic building blocks. These basic building blocks have nanoscale features and play a major role in achieving combined stiffening, strengthening and toughening mechanisms. Bioinspired nanocomposites based on these basic building blocks, regularly and stairwise staggered arrangements of hard platelets in soft matrix, have huge potential for developing advanced materials. The study of applicability of mechanical principles of biological materials to engineered materials will guide designing advanced materials. To probe the generic mechanical characteristics of these bioinspired nanocomposites, the model material concept in molecular dynamics (MD) is used. In this paper, the effect of platelets aspect ratio (AR) on the mechanical behaviour of bioinspired nanocomposites is investigated. The obtained Young׳s moduli of both the models and the strengths of the regularly staggered models agree with the available theories. However, the strengths of the stairwise staggered models show significant difference. For the stairwise staggered model, we demonstrate the existence of two critical ARs, a smaller critical AR above which platelet fracture occurs and a higher critical AR above which composite strength remains constant. Our MD study also shows the existence of mechanisms of platelet pull-out and breakage for lower and higher ARs. Pullout mechanism acts as a major source of plasticity. Further, we find that the regularly staggered model can achieve an optimal combination of high Young׳s modulus, flow strength and toughness, and the stairwise staggered model is efficient in obtaining high Young׳s modulus and tensile strength. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Bacterial Chemotaxis: The Early Years of Molecular Studies

    PubMed Central

    Hazelbauer, Gerald L.

    2014-01-01

    This review focuses on the early years of molecular studies of bacterial chemotaxis and motility, beginning in the 1960s with Julius Adler's pioneering work. It describes key observations that established the field and made bacterial chemotaxis a paradigm for the molecular understanding of biological signaling. Consideration of those early years includes aspects of science seldom described in journals: the accidental findings, personal interactions, and scientific culture that often drive scientific progress. PMID:22994495

  18. Ares I Integrated Vehicle System Safety Team

    NASA Technical Reports Server (NTRS)

    Wetherholt, Jon; McNairy, Lisa; Shackelford, Carla

    2009-01-01

    Complex systems require integrated analysis teams which sometimes are divided into subsystem teams. Proper division of the analysis in to subsystem teams is important. Safety analysis is one of the most difficult aspects of integration.

  19. Systematic study of imidazoles inhibiting IDO1 via the integration of molecular mechanics and quantum mechanics calculations.

    PubMed

    Zou, Yi; Wang, Fang; Wang, Yan; Guo, Wenjie; Zhang, Yihua; Xu, Qiang; Lai, Yisheng

    2017-05-05

    Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design. Copyright © 2017. Published by Elsevier Masson SAS.

  20. Elementary Education Pre-Service Teachers' Development of Mathematics Technology Integration Skills in a Technology Integration Course

    ERIC Educational Resources Information Center

    Polly, Drew

    2015-01-01

    Preparing pre-service teachers to effectively integrate technology in the classroom requires rich experiences that deepen their knowledge of technology, pedagogy, and content and the intersection of these aspects. This study examined elementary education pre-service teachers' development of skills and knowledge in a technology integration course…

  1. Is Judgement of Biotechnological Ethical Aspects Related to High School Students' Knowledge?

    ERIC Educational Resources Information Center

    Crne-Hladnik, Helena; Hladnik, Ales; Javornik, Branka; Kosmelj, Katarina; Peklaj, Cirila

    2012-01-01

    Quantitative and qualitative studies of various aspects of the perception of biotechnology were conducted among 469 Slovenian high school students of average age 17 years. Our research aimed to explore relationships among students' pre-knowledge of molecular and human genetics, and their attitudes to four specific biotechnological applications.…

  2. Principal Aspects Regarding the Maintenance of Mammalian Mitochondrial Genome Integrity.

    PubMed

    Vasileiou, Panagiotis V S; Mourouzis, Iordanis; Pantos, Constantinos

    2017-08-22

    Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA. Despite the extensive research that has been made regarding nuclear genome instability, the importance of mitochondrial genome integrity has only recently begun to be elucidated. The specific architecture and repair mechanisms of mitochondrial DNA, as well as the dynamic behavior that mitochondria exert regarding fusion, fission, and autophagy participate in mitochondrial genome stability, and therefore, cell homeostasis.

  3. Aspects of the Cognitive Model of Physics Problem Solving.

    ERIC Educational Resources Information Center

    Brekke, Stewart E.

    Various aspects of the cognitive model of physics problem solving are discussed in detail including relevant cues, encoding, memory, and input stimuli. The learning process involved in the recognition of familiar and non-familiar sensory stimuli is highlighted. Its four components include selection, acquisition, construction, and integration. The…

  4. Chopped molecular beam multiplexing system

    NASA Technical Reports Server (NTRS)

    Adams, Billy R. (Inventor)

    1986-01-01

    The integration of a chopped molecular beam mass spectrometer with a time multiplexing system is described. The chopping of the molecular beam is synchronized with the time intervals by a phase detector and a synchronous motor. Arithmetic means are generated for phase shifting the chopper with respect to the multiplexer. A four channel amplifier provides the capacity to independently vary the baseline and amplitude in each channel of the multiplexing system.

  5. Integrative taxonomy: Combining morphological, molecular and chemical data for species delineation in the parthenogenetic Trhypochthonius tectorum complex (Acari, Oribatida, Trhypochthoniidae)

    PubMed Central

    2011-01-01

    Background There is a long-standing controversial about how parthenogenetic species can be defined in absence of a generally accepted species concept for this reproductive mode. An integrative approach was suggested, combining molecular and morphological data to identify distinct monophyletic entities. Using this approach, speciation of parthenogenetic lineages was recently demonstrated for groups of bdelloid rotifers and oribatid mites. Trhypochthonius tectorum, an oribatid mite from the entirely parthenogenetic desmonomatan family Trhypochthoniidae, is traditionally treated as a single species in Central Europe. However, two new morphological lineages were recently proposed for some Austrian populations of T. tectorum, and were described as novel subspecies (T. silvestris europaeus) or form (T. japonicus forma occidentalis). We used the morphological and morphometrical data which led to this separation, and added mitochondrial and nuclear DNA sequences and the chemical composition of complex exocrine oil gland secretions to test this taxonomical hypothesis. This is the first attempt to combine these three types of data for integrative taxonomical investigations of oribatid mites. Results We show that the previous European species T. tectorum represents a species complex consisting of three distinct lineages in Austria (T.tectorum, T. silvestris europaeus and T. japonicus forma occidentalis), each clearly separated by morphology, oil gland secretion profiles and mitochondrial cox1 sequences. This diversification happened in the last ten million years. In contrast to these results, no variation among the lineages was found in the nuclear 18S rDNA. Conclusions Our approach combined morphological, molecular and chemical data to investigate diversity and species delineation in a parthenogenetic oribatid mite species complex. To date, hypotheses of a general oribatid mite phylogeny are manifold, and mostly based on single-method approaches. Probably, the integrative

  6. Molecular vibrational energy flow

    NASA Astrophysics Data System (ADS)

    Gruebele, M.; Bigwood, R.

    This article reviews some recent work in molecular vibrational energy flow (IVR), with emphasis on our own computational and experimental studies. We consider the problem in various representations, and use these to develop a family of simple models which combine specific molecular properties (e.g. size, vibrational frequencies) with statistical properties of the potential energy surface and wavefunctions. This marriage of molecular detail and statistical simplification captures trends of IVR mechanisms and survival probabilities beyond the abilities of purely statistical models or the computational limitations of full ab initio approaches. Of particular interest is IVR in the intermediate time regime, where heavy-atom skeletal modes take over the IVR process from hydrogenic motions even upon X H bond excitation. Experiments and calculations on prototype heavy-atom systems show that intermediate time IVR differs in many aspects from the early stages of hydrogenic mode IVR. As a result, IVR can be coherently frozen, with potential applications to selective chemistry.

  7. Current trends in molecular sensing

    NASA Astrophysics Data System (ADS)

    Wlodarski, Wojtek

    1992-08-01

    The biosphere contains a myriad of substances which can influence or stimulate various aspects of the health and behavior of living organisms. Not surprisingly, in the last decade or so researchers have appreciated the potential of developing a range of molecular sensor technologies, designed to estimate and monitor biological and chemical substances with a view to eventually controlling the biological processes themselves. This development has been accelerated recently by the realization that molecular sensors offer considerable commercial potential. At the same time, it was quickly appreciated that such sensors could revolutionize several areas, including health care, pollution and contamination monitoring, agriculture, on-line monitoring and control of industrial chemical processing, and strategic and tactical monitoring of chemical warfare. This brief review considers the changing scene in molecular sensor research by reference to a few key examples.

  8. Suicide Prevention in the Dot Com Era: Technological Aspects of a University Suicide Prevention Program

    ERIC Educational Resources Information Center

    Manning, Jessica; VanDeusen, Karen

    2011-01-01

    Western Michigan University's Suicide Prevention Program utilizes multiple technological components, including an online training course, a Web site, and 2 social networking Web site profiles, as integral aspects of a comprehensive program. This article discusses the development, maintenance, use, and impact of the technological aspects of this…

  9. Computing molecular fluctuations in biochemical reaction systems based on a mechanistic, statistical theory of irreversible processes.

    PubMed

    Kulasiri, Don

    2011-01-01

    We discuss the quantification of molecular fluctuations in the biochemical reaction systems within the context of intracellular processes associated with gene expression. We take the molecular reactions pertaining to circadian rhythms to develop models of molecular fluctuations in this chapter. There are a significant number of studies on stochastic fluctuations in intracellular genetic regulatory networks based on single cell-level experiments. In order to understand the fluctuations associated with the gene expression in circadian rhythm networks, it is important to model the interactions of transcriptional factors with the E-boxes in the promoter regions of some of the genes. The pertinent aspects of a near-equilibrium theory that would integrate the thermodynamical and particle dynamic characteristics of intracellular molecular fluctuations would be discussed, and the theory is extended by using the theory of stochastic differential equations. We then model the fluctuations associated with the promoter regions using general mathematical settings. We implemented ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in biochemical networks, for each of the motifs. Both the theory and the Gillespie's algorithms gave the same results in terms of the time evolution of means and variances of molecular numbers. As biochemical reactions occur far away from equilibrium-hence the use of the Gillespie algorithm-these results suggest that the near-equilibrium theory should be a good approximation for some of the biochemical reactions. © 2011 Elsevier Inc. All rights reserved.

  10. Principal Aspects Regarding the Maintenance of Mammalian Mitochondrial Genome Integrity

    PubMed Central

    Vasileiou, Panagiotis V. S.; Mourouzis, Iordanis; Pantos, Constantinos

    2017-01-01

    Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA. Despite the extensive research that has been made regarding nuclear genome instability, the importance of mitochondrial genome integrity has only recently begun to be elucidated. The specific architecture and repair mechanisms of mitochondrial DNA, as well as the dynamic behavior that mitochondria exert regarding fusion, fission, and autophagy participate in mitochondrial genome stability, and therefore, cell homeostasis. PMID:28829360

  11. A molecular shift register based on electron transfer

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  12. A National Comparison of Biochemistry and Molecular Biology Capstone Experiences

    ERIC Educational Resources Information Center

    Aguanno, Ann; Mertz, Pamela; Martin, Debra; Bell, Ellis

    2015-01-01

    Recognizing the increasingly integrative nature of the molecular life sciences, the "American Society for Biochemistry and Molecular Biology" (ASBMB) recommends that Biochemistry and Molecular Biology (BMB) programs develop curricula based on concepts, content, topics, and expected student outcomes, rather than courses. To that end,…

  13. An Integrated Molecular Database on Indian Insects.

    PubMed

    Pratheepa, Maria; Venkatesan, Thiruvengadam; Gracy, Gandhi; Jalali, Sushil Kumar; Rangheswaran, Rajagopal; Antony, Jomin Cruz; Rai, Anil

    2018-01-01

    MOlecular Database on Indian Insects (MODII) is an online database linking several databases like Insect Pest Info, Insect Barcode Information System (IBIn), Insect Whole Genome sequence, Other Genomic Resources of National Bureau of Agricultural Insect Resources (NBAIR), Whole Genome sequencing of Honey bee viruses, Insecticide resistance gene database and Genomic tools. This database was developed with a holistic approach for collecting information about phenomic and genomic information of agriculturally important insects. This insect resource database is available online for free at http://cib.res.in. http://cib.res.in/.

  14. The Development and Comparison of Molecular Dynamics Simulation and Monte Carlo Simulation

    NASA Astrophysics Data System (ADS)

    Chen, Jundong

    2018-03-01

    Molecular dynamics is an integrated technology that combines physics, mathematics and chemistry. Molecular dynamics method is a computer simulation experimental method, which is a powerful tool for studying condensed matter system. This technique not only can get the trajectory of the atom, but can also observe the microscopic details of the atomic motion. By studying the numerical integration algorithm in molecular dynamics simulation, we can not only analyze the microstructure, the motion of particles and the image of macroscopic relationship between them and the material, but can also study the relationship between the interaction and the macroscopic properties more conveniently. The Monte Carlo Simulation, similar to the molecular dynamics, is a tool for studying the micro-molecular and particle nature. In this paper, the theoretical background of computer numerical simulation is introduced, and the specific methods of numerical integration are summarized, including Verlet method, Leap-frog method and Velocity Verlet method. At the same time, the method and principle of Monte Carlo Simulation are introduced. Finally, similarities and differences of Monte Carlo Simulation and the molecular dynamics simulation are discussed.

  15. Significance and integration of molecular diagnostics in the framework of veterinary practice.

    PubMed

    Aranaz, Alicia

    2015-01-01

    The field of molecular diagnostics in veterinary practice is rapidly evolving. An array of molecular techniques of different complexity is available to facilitate the fast and specific diagnosis of animal diseases. The choice for the adequate technique is dependent on the mission and attributions of the laboratory and requires both a knowledge of the molecular biology basis and of its limitations. The ability to quickly detect pathogens and their characteristics would allow for precise decision-making and target measures such as prophylaxis, appropriate therapy, and biosafety plans to control disease outbreaks. In practice, taking benefit of the huge amount of data that can be obtained using molecular techniques highlights the need of collaboration between veterinarians in the laboratory and practitioners.

  16. Information storage at the molecular level - The design of a molecular shift register memory

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

    The control of electron transfer rates is discussed and a molecular shift register memory at the molecular level is described. The memory elements are made up of molecules which can exist in either an oxidized or reduced state and the bits can be shifted between the cells with photoinduced electron transfer reactions. The device integrates designed molecules onto a VLSI substrate. A control structure to modify the flow of information along a shift register is indicated schematically.

  17. Molecular evolution: concepts and the origin of disciplines.

    PubMed

    Suárez-Díaz, Edna

    2009-03-01

    This paper focuses on the consolidation of Molecular Evolution, a field originating in the 1960s at the interface of molecular biology, biochemistry, evolutionary biology, biophysics and studies on the origin of life and exobiology. The claim is made that Molecular Evolution became a discipline by integrating different sorts of scientific traditions: experimental, theoretical and comparative. The author critically incorporates Timothy Lenoir's treatment of disciplines (1997), as well as ideas developed by Stephen Toulmin (1962) on the same subject. On their account disciplines are spaces where the social and epistemic dimensions of science are deeply and complexly interwoven. However, a more detailed account of discipline formation and the dynamics of an emerging disciplinary field is lacking in their analysis. The present essay suggests focusing on the role of scientific concepts in the double configuration of disciplines: the social/political and the epistemic order. In the case of Molecular Evolution the concepts of molecular clock and informational molecules played a central role, both in differentiating molecular from classical evolutionists, and in promoting communication between the different sorts of traditions integrated in Molecular Evolution. The paper finishes with a reflection on the historicity of disciplines, and the historicity of our concepts of disciplines.

  18. Fast dimension reduction and integrative clustering of multi-omics data using low-rank approximation: application to cancer molecular classification.

    PubMed

    Wu, Dingming; Wang, Dongfang; Zhang, Michael Q; Gu, Jin

    2015-12-01

    One major goal of large-scale cancer omics study is to identify molecular subtypes for more accurate cancer diagnoses and treatments. To deal with high-dimensional cancer multi-omics data, a promising strategy is to find an effective low-dimensional subspace of the original data and then cluster cancer samples in the reduced subspace. However, due to data-type diversity and big data volume, few methods can integrative and efficiently find the principal low-dimensional manifold of the high-dimensional cancer multi-omics data. In this study, we proposed a novel low-rank approximation based integrative probabilistic model to fast find the shared principal subspace across multiple data types: the convexity of the low-rank regularized likelihood function of the probabilistic model ensures efficient and stable model fitting. Candidate molecular subtypes can be identified by unsupervised clustering hundreds of cancer samples in the reduced low-dimensional subspace. On testing datasets, our method LRAcluster (low-rank approximation based multi-omics data clustering) runs much faster with better clustering performances than the existing method. Then, we applied LRAcluster on large-scale cancer multi-omics data from TCGA. The pan-cancer analysis results show that the cancers of different tissue origins are generally grouped as independent clusters, except squamous-like carcinomas. While the single cancer type analysis suggests that the omics data have different subtyping abilities for different cancer types. LRAcluster is a very useful method for fast dimension reduction and unsupervised clustering of large-scale multi-omics data. LRAcluster is implemented in R and freely available via http://bioinfo.au.tsinghua.edu.cn/software/lracluster/ .

  19. Adaptively restrained molecular dynamics in LAMMPS

    NASA Astrophysics Data System (ADS)

    Kant Singh, Krishna; Redon, Stephane

    2017-07-01

    Adaptively restrained molecular dynamics (ARMD) is a recently introduced particles simulation method that switches positional degrees of freedom on and off during simulation in order to speed up calculations. In the NVE ensemble, ARMD allows users to trade between precision and speed while, in the NVT ensemble, it makes it possible to compute statistical averages faster. Despite the conceptual simplicity of the approach, however, integrating it in existing molecular dynamics packages is non-trivial, in particular since implemented potentials should a priori be rewritten to take advantage of frozen particles and achieve a speed-up. In this paper, we present novel algorithms for integrating ARMD in LAMMPS, a popular multi-purpose molecular simulation package. In particular, we demonstrate how to enable ARMD in LAMMPS without having to re-implement all available force fields. The proposed algorithms are assessed on four different benchmarks, and show how they allow us to speed up simulations up to one order of magnitude.

  20. Interactions of elevation, aspect, and slope in models of forest species composition and productivity

    Treesearch

    Albert R. Stage; Christian Salas

    2007-01-01

    We present a linear model for the interacting effects of elevation, aspect, and slope for use in predicting forest productivity or species composition. The model formulation we propose integrates interactions of these three factors in a mathematical expression representing their combined effect in terms of a cosine function of aspect with a phase shift and amplitude...

  1. Molecular, Cellular and Pharmaceutical Aspects of Biomaterials in Dentistry and Oral and Maxillofacial Surgery. An Internationalization of Higher Education and Research Perspective.

    PubMed

    Wisniewska, Lidia M; Dohan Ehrenfest, David M; Galindo-Moreno, Pablo; Segovia, Jesus D; Inchingolo, Francesco; Wang, Hom-Lay; Fernandes-Cruz, Manuel

    2017-01-01

    In dentistry and oral and maxillofacial surgery, the development of implantable biomaterials and the understanding of their molecular, cellular and pharmaceutical aspects are currently major fields of research and education, with a considerable impact on the daily clinical practice and the evolution of therapeutic strategies. In the era of globalized economy of knowledge and science, this scientific domain needs the development of global cooperation and a paradigm evolution in the organizational culture of the dental sciences and related dental industry. Despite political pressure and theoretical efforts, the internationalization of higher education and research today in dentistry and biomaterials remains in general quite superficial and mostly dependent on the efforts of a few leaders of internationalization working through their personal networks, as it was assessed through the FAST scores (Fast Assessment Screening Test) calculated in various dental schools and groups worldwide through the ISAIAS program (Intercultural Sensitivity Academic Index &Advanced Standards). Cooperation in a multipolar multicultural community requires the development of strong intercultural competences, and this process remains limited in most institutions. These limits of international scientific cooperation can be observed through different markers, particularly the difficult and limited production of ISO standards (International Organization for Standardization) and the relatively low SCIENTI scores (Scientific Cooperation Internationalization Effort &Network Test &Index) of the specialized dental literature, particularly in comparison to the most significant medical literature. However, as an analytical tool to assess the scientific international cooperation effort between fields and periods, the SCIENTI screening system also highlighted a significant increase of the internationalization effort in the last years in the best dental biomaterials publications. Finally, an

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  3. Elements for successful sensor-based process control {Integrated Metrology}

    NASA Astrophysics Data System (ADS)

    Butler, Stephanie Watts

    1998-11-01

    Current productivity needs have stimulated development of alternative metrology, control, and equipment maintenance methods. Specifically, sensor applications provide the opportunity to increase productivity, tighten control, reduce scrap, and improve maintenance schedules and procedures. Past experience indicates a complete integrated solution must be provided for sensor-based control to be used successfully in production. In this paper, Integrated Metrology is proposed as the term for an integrated solution that will result in a successful application of sensors for process control. This paper defines and explores the perceived four elements of successful sensor applications: business needs, integration, components, and form. Based upon analysis of existing successful commercially available controllers, the necessary business factors have been determined to be strong, measurable industry-wide business needs whose solution is profitable and feasible. This paper examines why the key aspect of integration is the decision making process. A detailed discussion is provided of the components of most importance to sensor based control: decision-making methods, the 3R's of sensors, and connectivity. A metric for one of the R's (resolution) is proposed to allow focus on this important aspect of measurement. A form for these integrated components which synergistically partitions various aspects of control at the equipment and MES levels to efficiently achieve desired benefits is recommended.

  4. Silicon sample holder for molecular beam epitaxy on pre-fabricated integrated circuits

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael E. (Inventor); Grunthaner, Paula J. (Inventor); Grunthaner, Frank J. (Inventor)

    1994-01-01

    The sample holder of the invention is formed of the same semiconductor crystal as the integrated circuit on which the molecular beam expitaxial process is to be performed. In the preferred embodiment, the sample holder comprises three stacked micro-machined silicon wafers: a silicon base wafer having a square micro-machined center opening corresponding in size and shape to the active area of a CCD imager chip, a silicon center wafer micro-machined as an annulus having radially inwardly pointing fingers whose ends abut the edges of and center the CCD imager chip within the annulus, and a silicon top wafer micro-machined as an annulus having cantilevered membranes which extend over the top of the CCD imager chip. The micro-machined silicon wafers are stacked in the order given above with the CCD imager chip centered in the center wafer and sandwiched between the base and top wafers. The thickness of the center wafer is about 20% less than the thickness of the CCD imager chip. Preferably, four titanium wires, each grasping the edges of the top and base wafers, compress all three wafers together, flexing the cantilever fingers of the top wafer to accommodate the thickness of the CCD imager chip, acting as a spring holding the CCD imager chip in place.

  5. Structure and Dynamics of the Instantaneous Water/Vapor Interface Revisited by Path-Integral and Ab Initio Molecular Dynamics Simulations.

    PubMed

    Kessler, Jan; Elgabarty, Hossam; Spura, Thomas; Karhan, Kristof; Partovi-Azar, Pouya; Hassanali, Ali A; Kühne, Thomas D

    2015-08-06

    The structure and dynamics of the water/vapor interface is revisited by means of path-integral and second-generation Car-Parrinello ab initio molecular dynamics simulations in conjunction with an instantaneous surface definition [Willard, A. P.; Chandler, D. J. Phys. Chem. B 2010, 114, 1954]. In agreement with previous studies, we find that one of the OH bonds of the water molecules in the topmost layer is pointing out of the water into the vapor phase, while the orientation of the underlying layer is reversed. Therebetween, an additional water layer is detected, where the molecules are aligned parallel to the instantaneous water surface.

  6. Natural genetic variation for morphological and molecular determinants of plant growth and yield.

    PubMed

    Nunes-Nesi, Adriano; Nascimento, Vitor de Laia; de Oliveira Silva, Franklin Magnum; Zsögön, Agustin; Araújo, Wagner L; Sulpice, Ronan

    2016-05-01

    The rates of increase in yield of the main commercial crops have been steadily falling in many areas worldwide. This generates concerns because there is a growing demand for plant biomass due to the increasing population. Plant yield should thus be improved in the context of climate change and decreasing natural resources. It is a major challenge which could be tackled by improving and/or altering light-use efficiency, CO2 uptake and fixation, primary metabolism, plant architecture and leaf morphology, and developmental plant processes. In this review, we discuss some of the traits which could lead to yield increase, with a focus on how natural genetic variation could be harnessed. Moreover, we provide insights for advancing our understanding of the molecular aspects governing plant growth and yield, and propose future avenues for improvement of crop yield. We also suggest that knowledge accumulated over the last decade in the field of molecular physiology should be integrated into new ideotypes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Molecular mimicry between protein and tRNA.

    PubMed

    Nakamura, Y

    2001-01-01

    Mimicry is a sophisticated development in animals, fish, and plants that allows them to fool others by imitating a shape or color for diverse purposes, such as to prey, evade, lure, pollinate, or threaten. This is not restricted to the macro-world, but extends to the micro-world as molecular mimicry. Recent advances in structural and molecular biology uncovered a set of translation factors that resembles a tRNA shape and, in one case, even mimics a tRNA function for deciphering the genetic code. Nature must have evolved this art of molecular mimicry between protein and ribonucleic acid by using different protein structures until the translation factors sat in the cockpit of a ribosome machine, on behalf of tRNA, and achieved diverse actions. Structural, functional, and evolutionary aspects of molecular mimicry will be discussed.

  8. The molecular biology of inflammatory bowel diseases.

    PubMed

    Corfield, Anthony P; Wallace, Heather M; Probert, Chris S J

    2011-08-01

    IBDs (inflammatory bowel diseases) are a group of diseases affecting the gastrointestinal tract. The diseases are multifactorial and cover genetic aspects: susceptibility genes, innate and adaptive responses to inflammation, and structure and efficacy of the mucosal protective barrier. Animal models of IBD have been developed to gain further knowledge of the disease mechanisms. These topics form an overlapping background to enable an improved understanding of the molecular features of these diseases. A series of articles is presented based on the topics covered at the Biochemical Society Focused Meeting The Molecular Biology of Inflammatory Bowel Diseases.

  9. Vapor-solid-solid grown Ge nanowires at integrated circuit compatible temperature by molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Zhu, Zhongyunshen; Song, Yuxin; Zhang, Zhenpu; Sun, Hao; Han, Yi; Li, Yaoyao; Zhang, Liyao; Xue, Zhongying; Di, Zengfeng; Wang, Shumin

    2017-09-01

    We demonstrate Au-assisted vapor-solid-solid (VSS) growth of Ge nanowires (NWs) by molecular beam epitaxy at the substrate temperature of ˜180 °C, which is compatible with the temperature window for Si-based integrated circuit. Low temperature grown Ge NWs hold a smaller size, similar uniformity, and better fit with Au tips in diameter, in contrast to Ge NWs grown at around or above the eutectic temperature of Au-Ge alloy in the vapor-liquid-solid (VLS) growth. Six ⟨110⟩ growth orientations were observed on Ge (110) by the VSS growth at ˜180 °C, differing from only one vertical growth direction of Ge NWs by the VLS growth at a high temperature. The evolution of NWs dimension and morphology from the VLS growth to the VSS growth is qualitatively explained by analyzing the mechanism of the two growth modes.

  10. Assessment of sperm nucleus integrity in infertile men: a novel research field for anthropology in the molecular era.

    PubMed

    Lavranos, Giagkos; Manolakou, Panagiota; Katsiki, Evangelia; Angelopoulou, Roxani

    2013-12-01

    Anthropology has always been particularly interested in the origin of human life and the development towards adulthood. Although originally working with skeletal measurements and bio-morphological markers in modern populations, it has now entered the growing field of applied molecular biology. This relatively recent advance allows the detailed study of major events in human development and senescence. For instance, sperm DNA integrity and chromatin re-organization are crucial factors for fertilization and embryo development. Clinical researchers have developed improved methods for the evaluation of DNA integrity and protaminosis in sperm nuclei, such as the TUNEL and the CMA3 assays. DNA damage in spermatozoal nuclei is detected using the TUNEL assay which depends on the specific enzymatic reaction of TdT with the end strand breaks of DNA. Protaminosis in spermatozoal nucleus is evaluated using CMA3 assay, which is based on the in situ competition between CMA3 and protamines. Such measurements may provide useful data on human reproductive health, aiding the explanation of demographic differences across the world.

  11. Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics

    NASA Astrophysics Data System (ADS)

    Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C.; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

    2017-03-01

    Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

  12. Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics.

    PubMed

    Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

    2017-03-30

    Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

  13. Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria

    PubMed Central

    Minias, Alina; van Ingen, Jakko; Rastogi, Nalin; Brzostek, Anna; Żaczek, Anna; Dziadek, Jarosław

    2016-01-01

    SUMMARY Molecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting techniques, many traditional concepts regarding transmission, infectivity, or pathogenicity of mycobacterial bacilli have been revisited, and their conventional interpretations have been challenged. Since the mid-1990s, when the first typing methods were introduced, a plethora of other modalities have been proposed. So-called molecular epidemiology has become an essential subdiscipline of modern mycobacteriology. It serves as a resource for understanding the key issues in the epidemiology of tuberculosis and other mycobacterial diseases. Among these issues are disclosing sources of infection, quantifying recent transmission, identifying transmission links, discerning reinfection from relapse, tracking the geographic distribution and clonal expansion of specific strains, and exploring the genetic mechanisms underlying specific phenotypic traits, including virulence, organ tropism, transmissibility, or drug resistance. Since genotyping continues to unravel the biology of mycobacteria, it offers enormous promise in the fight against and prevention of the diseases caused by these pathogens. In this review, molecular typing methods for Mycobacterium tuberculosis and nontuberculous mycobacteria elaborated over the last 2 decades are summarized. The relevance of these methods to the epidemiological investigation, diagnosis, evolution, and control of mycobacterial diseases is discussed. PMID:26912567

  14. Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics: strength in unity.

    PubMed

    Papaleo, Elena

    2015-01-01

    In the last years, we have been observing remarkable improvements in the field of protein dynamics. Indeed, we can now study protein dynamics in atomistic details over several timescales with a rich portfolio of experimental and computational techniques. On one side, this provides us with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome their own limitations. Moreover, now that we have the means to study protein dynamics in great details, we need new tools to understand the information embedded in the protein ensembles and in their dynamic signature. With this aim in mind, we should enrich the current tools for analysis of biomolecular simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations.

  15. Small business development for molecular diagnostics.

    PubMed

    Anagostou, Anthanasia; Liotta, Lance A

    2012-01-01

    Molecular profiling, which is the application of molecular diagnostics technology to tissue and blood -specimens, is an integral element in the new era of molecular medicine and individualized therapy. Molecular diagnostics is a fertile ground for small business development because it can generate products that meet immediate demands in the health-care sector: (a) Detection of disease risk, or early-stage disease, with a higher specificity and sensitivity compared to previous testing methods, and (b) "Companion diagnostics" for stratifying patients to receive a treatment choice optimized to their individual disease. This chapter reviews the promise and challenges of business development in this field. Guidelines are provided for the creation of a business model and the generation of a marketing plan around a candidate molecular diagnostic product. Steps to commercialization are outlined using existing molecular diagnostics companies as learning examples.

  16. Detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR) and molecular characterization in cervical cancer cells.

    PubMed

    Luft, F; Klaes, R; Nees, M; Dürst, M; Heilmann, V; Melsheimer, P; von Knebel Doeberitz, M

    2001-04-01

    Human papillomavirus (HPV) genomes usually persist as episomal molecules in HPV associated preneoplastic lesions whereas they are frequently integrated into the host cell genome in HPV-related cancers cells. This suggests that malignant conversion of HPV-infected epithelia is linked to recombination of cellular and viral sequences. Due to technical limitations, precise sequence information on viral-cellular junctions were obtained only for few cell lines and primary lesions. In order to facilitate the molecular analysis of genomic HPV integration, we established a ligation-mediated PCR assay for the detection of integrated papillomavirus sequences (DIPS-PCR). DIPS-PCR was initially used to amplify genomic viral-cellular junctions from HPV-associated cervical cancer cell lines (C4-I, C4-II, SW756, and HeLa) and HPV-immortalized keratinocyte lines (HPKIA, HPKII). In addition to junctions already reported in public data bases, various new fusion fragments were identified. Subsequently, 22 different viral-cellular junctions were amplified from 17 cervical carcinomas and 1 vulval intraepithelial neoplasia (VIN III). Sequence analysis of each junction revealed that the viral E1 open reading frame (ORF) was fused to cellular sequences in 20 of 22 (91%) cases. Chromosomal integration loci mapped to chromosomes 1 (2n), 2 (3n), 7 (2n), 8 (3n), 10 (1n), 14 (5n), 16 (1n), 17 (2n), and mitochondrial DNA (1n), suggesting random distribution of chromosomal integration sites. Precise sequence information obtained by DIPS-PCR was further used to monitor the monoclonal origin of 4 cervical cancers, 1 case of recurrent premalignant lesions and 1 lymph node metastasis. Therefore, DIPS-PCR might allow efficient therapy control and prediction of relapse in patients with HPV-associated anogenital cancers. Copyright 2001 Wiley-Liss, Inc.

  17. Choosing the Right Systems Integration

    NASA Astrophysics Data System (ADS)

    Péči, Matúš; Važan, Pavel

    2014-12-01

    The paper examines systems integration and its main levels at higher levels of control. At present, the systems integration is one of the main aspects participating in the consolidation processes and financial flows of a company. Systems Integration is a complicated emotionconsuming process and it is often a problem to choose the right approach and level of integration. The research focused on four levels of integration, while each of them is characterized by specific conditions. At each level, there is a summary of recommendations and practical experience. The paper also discusses systems integration between the information and MES levels. The main part includes user-level integration where we describe an example of such integration. Finally, we list recommendations and also possible predictions of the systems integration as one of the important factors in the future.

  18. The Glutamatergic Aspects of Schizophrenia Molecular Pathophysiology: Role of the Postsynaptic Density, and Implications for Treatment

    PubMed Central

    Iasevoli, Felice; Tomasetti, Carmine; Buonaguro, Elisabetta F.; de Bartolomeis, Andrea

    2014-01-01

    Schizophrenia is one of the most debilitating psychiatric diseases with a lifetime prevalence of approximately 1%. Although the specific molecular underpinnings of schizophrenia are still unknown, evidence has long linked its pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is among the molecular structures suggested to be potentially involved in schizophrenia. More specifically, the PSD is an electron-dense thickening of glutamatergic synapses, including ionotropic and metabotropic glutamate receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling molecules. Being implicated in the postsynaptic signaling of multiple neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an ideal candidate for studying dopamine-glutamate disturbances in schizophrenia. Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer are implicated in severe behavioral disorders, including schizophrenia. These findings, further corroborated by genetic and animal studies of schizophrenia, offer new insights for the development of pharmacological strategies able to overcome the limitations in terms of efficacy and side effects of current schizophrenia treatment. Indeed, PSD proteins are now being considered as potential molecular targets against this devastating illness. The current paper reviews the most recent hypotheses on the molecular mechanisms underlying schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in schizophrenia and we provide an update on postsynaptic molecules involvement in schizophrenia pathophysiology by addressing both human and animal studies. Finally, the possibility that PSD proteins may represent potential targets for new molecular interventions in psychosis will be discussed. PMID:24851087

  19. Dancing through Life: Molecular Dynamics Simulations and Network-Centric Modeling of Allosteric Mechanisms in Hsp70 and Hsp110 Chaperone Proteins.

    PubMed

    Stetz, Gabrielle; Verkhivker, Gennady M

    2015-01-01

    Hsp70 and Hsp110 chaperones play an important role in regulating cellular processes that involve protein folding and stabilization, which are essential for the integrity of signaling networks. Although many aspects of allosteric regulatory mechanisms in Hsp70 and Hsp110 chaperones have been extensively studied and significantly advanced in recent experimental studies, the atomistic picture of signal propagation and energetics of dynamics-based communication still remain unresolved. In this work, we have combined molecular dynamics simulations and protein stability analysis of the chaperone structures with the network modeling of residue interaction networks to characterize molecular determinants of allosteric mechanisms. We have shown that allosteric mechanisms of Hsp70 and Hsp110 chaperones may be primarily determined by nucleotide-induced redistribution of local conformational ensembles in the inter-domain regions and the substrate binding domain. Conformational dynamics and energetics of the peptide substrate binding with the Hsp70 structures has been analyzed using free energy calculations, revealing allosteric hotspots that control negative cooperativity between regulatory sites. The results have indicated that cooperative interactions may promote a population-shift mechanism in Hsp70, in which functional residues are organized in a broad and robust allosteric network that can link the nucleotide-binding site and the substrate-binding regions. A smaller allosteric network in Hsp110 structures may elicit an entropy-driven allostery that occurs in the absence of global structural changes. We have found that global mediating residues with high network centrality may be organized in stable local communities that are indispensable for structural stability and efficient allosteric communications. The network-centric analysis of allosteric interactions has also established that centrality of functional residues could correlate with their sensitivity to mutations

  20. Dancing through Life: Molecular Dynamics Simulations and Network-Centric Modeling of Allosteric Mechanisms in Hsp70 and Hsp110 Chaperone Proteins

    PubMed Central

    Stetz, Gabrielle; Verkhivker, Gennady M.

    2015-01-01

    Hsp70 and Hsp110 chaperones play an important role in regulating cellular processes that involve protein folding and stabilization, which are essential for the integrity of signaling networks. Although many aspects of allosteric regulatory mechanisms in Hsp70 and Hsp110 chaperones have been extensively studied and significantly advanced in recent experimental studies, the atomistic picture of signal propagation and energetics of dynamics-based communication still remain unresolved. In this work, we have combined molecular dynamics simulations and protein stability analysis of the chaperone structures with the network modeling of residue interaction networks to characterize molecular determinants of allosteric mechanisms. We have shown that allosteric mechanisms of Hsp70 and Hsp110 chaperones may be primarily determined by nucleotide-induced redistribution of local conformational ensembles in the inter-domain regions and the substrate binding domain. Conformational dynamics and energetics of the peptide substrate binding with the Hsp70 structures has been analyzed using free energy calculations, revealing allosteric hotspots that control negative cooperativity between regulatory sites. The results have indicated that cooperative interactions may promote a population-shift mechanism in Hsp70, in which functional residues are organized in a broad and robust allosteric network that can link the nucleotide-binding site and the substrate-binding regions. A smaller allosteric network in Hsp110 structures may elicit an entropy-driven allostery that occurs in the absence of global structural changes. We have found that global mediating residues with high network centrality may be organized in stable local communities that are indispensable for structural stability and efficient allosteric communications. The network-centric analysis of allosteric interactions has also established that centrality of functional residues could correlate with their sensitivity to mutations

  1. Solvent Dependence of Double Proton Transfer in the Formic Acid-Formamidine Complex: Path Integral Molecular Dynamics Investigation.

    PubMed

    Kungwan, Nawee; Ngaojampa, Chanisorn; Ogata, Yudai; Kawatsu, Tsutomu; Oba, Yuki; Kawashima, Yukio; Tachikawa, Masanori

    2017-10-05

    Solvent dependence of double proton transfer in the formic acid-formamidine (FA-FN) complex at room temperature was investigated by means of ab initio path integral molecular dynamics (AIPIMD) simulation with taking nuclear quantum and thermal effects into account. The conductor-like screening model (COSMO) was applied for solvent effect. In comparison with gas phase, double proton delocalization between two heavy atoms (O and N) in FA-FN were observed with reduced proton transfer barrier height in low dielectric constant medium (<4.8). For dielectric constant medium at 4.8, the chance of finding these two protons are more pronounced due to the solvent effect which completely washes out the proton transfer barrier. In the case of higher dielectric constant medium (>4.8), the ionic species becomes more stable than the neutral ones and the formate anion and formamidium cation are thermodynamically stable. For ab initio molecular dynamics simulation, in low dielectric constant medium (<4.8) a reduction of proton transfer barrier with solvent effect is found to be less pronounced than the AIPIMD due to the absence of nuclear quantum effect. Moreover, the motions of FA-FN complex are significantly different with increasing dielectric constant medium. Such a difference is revealed in detail by the principal component analysis.

  2. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms

    ERIC Educational Resources Information Center

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections…

  3. Molecular dynamics simulations of collision-induced absorption: Implementation in LAMMPS

    NASA Astrophysics Data System (ADS)

    Fakhardji, W.; Gustafsson, M.

    2017-02-01

    We pursue simulations of collision-induced absorption in a mixture of argon and xenon gas at room temperature by means of classical molecular dynamics. The established theoretical approach (Hartmann et al. 2011 J. Chem. Phys. 134 094316) is implemented with the molecular dynamics package LAMMPS. The bound state features in the absorption spectrum are well reproduced with the molecular dynamics simulation in comparison with a laboratory measurement. The magnitude of the computed absorption, however, is underestimated in a large part of the spectrum. We suggest some aspects of the simulation that could be improved.

  4. Endometriosis: translation of molecular insights to management.

    PubMed

    Langan, K L; Farrell, M E; Keyser, E A; Salyer, B A; Burney, R O

    2014-09-01

    Endometriosis is a debilitating gynecologic disorder causing pelvic pain and infertility and characterized by the implantation of endometrial tissue to extrauterine locations. Though aspects of the condition remain enigmatic, the molecular pathophysiology of endometriosis appears to be clarifying. Estrogen dependence of the disease is a sentinel endocrine feature and reduction of estrogen bioavailability is the therapeutic principle upon which traditional treatment and prevention approaches have been based. Endometriosis is a chronic inflammatory condition associated with lesional neoangiogenesis and attenuated progesterone action at the level of the endometrium. The elucidation of the molecular pathways mediating these observations has revealed new targets for directed medical and surgical treatment. This paper will review current approaches to the management of endometriosis in the context of the molecular pathophysiology.

  5. (DCT) A Reconfigurable RF Photonics Unit Cell For Integrated Circuits

    DTIC Science & Technology

    2012-08-10

    Public Release In this work, the integration of a Quantum Dot Mode Locked Laser , that acts as a microwave and millimeter wave source, with a wideband...antenna is presented. Two aspects of research are discussed. The first aspect deals with a Mode Locked Laser (MLL) based on quantum dot (QD...designed antennas were integrated with laser chips using the lithographic method. The challenges of designing this wideband antenna that can operate

  6. Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.

    PubMed

    Ortiz, Michael V; Kobos, Rachel; Walsh, Michael; Slotkin, Emily K; Roberts, Stephen; Berger, Michael F; Hameed, Meera; Solit, David; Ladanyi, Marc; Shukla, Neerav; Kentsis, Alex

    2016-08-01

    Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations. This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence-Based Medicine. There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1-2), eight (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4). The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. The development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials. © 2016 Wiley Periodicals, Inc.

  7. Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations.

    PubMed

    Fang, Jiansong; Pang, Xiaocong; Wu, Ping; Yan, Rong; Gao, Li; Li, Chao; Lian, Wenwen; Wang, Qi; Liu, Ai-lin; Du, Guan-hua

    2016-05-01

    A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2)) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔEvdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives. © 2015 John Wiley & Sons A/S.

  8. Integrating quantitative thinking into an introductory biology course improves students' mathematical reasoning in biological contexts.

    PubMed

    Hester, Susan; Buxner, Sanlyn; Elfring, Lisa; Nagy, Lisa

    2014-01-01

    Recent calls for improving undergraduate biology education have emphasized the importance of students learning to apply quantitative skills to biological problems. Motivated by students' apparent inability to transfer their existing quantitative skills to biological contexts, we designed and taught an introductory molecular and cell biology course in which we integrated application of prerequisite mathematical skills with biology content and reasoning throughout all aspects of the course. In this paper, we describe the principles of our course design and present illustrative examples of course materials integrating mathematics and biology. We also designed an outcome assessment made up of items testing students' understanding of biology concepts and their ability to apply mathematical skills in biological contexts and administered it as a pre/postcourse test to students in the experimental section and other sections of the same course. Precourse results confirmed students' inability to spontaneously transfer their prerequisite mathematics skills to biological problems. Pre/postcourse outcome assessment comparisons showed that, compared with students in other sections, students in the experimental section made greater gains on integrated math/biology items. They also made comparable gains on biology items, indicating that integrating quantitative skills into an introductory biology course does not have a deleterious effect on students' biology learning.

  9. Integrating Quantitative Thinking into an Introductory Biology Course Improves Students’ Mathematical Reasoning in Biological Contexts

    PubMed Central

    Hester, Susan; Buxner, Sanlyn; Elfring, Lisa; Nagy, Lisa

    2014-01-01

    Recent calls for improving undergraduate biology education have emphasized the importance of students learning to apply quantitative skills to biological problems. Motivated by students’ apparent inability to transfer their existing quantitative skills to biological contexts, we designed and taught an introductory molecular and cell biology course in which we integrated application of prerequisite mathematical skills with biology content and reasoning throughout all aspects of the course. In this paper, we describe the principles of our course design and present illustrative examples of course materials integrating mathematics and biology. We also designed an outcome assessment made up of items testing students’ understanding of biology concepts and their ability to apply mathematical skills in biological contexts and administered it as a pre/postcourse test to students in the experimental section and other sections of the same course. Precourse results confirmed students’ inability to spontaneously transfer their prerequisite mathematics skills to biological problems. Pre/postcourse outcome assessment comparisons showed that, compared with students in other sections, students in the experimental section made greater gains on integrated math/biology items. They also made comparable gains on biology items, indicating that integrating quantitative skills into an introductory biology course does not have a deleterious effect on students’ biology learning. PMID:24591504

  10. Atomic spectral-product representations of molecular electronic structure: metric matrices and atomic-product composition of molecular eigenfunctions.

    PubMed

    Ben-Nun, M; Mills, J D; Hinde, R J; Winstead, C L; Boatz, J A; Gallup, G A; Langhoff, P W

    2009-07-02

    Recent progress is reported in development of ab initio computational methods for the electronic structures of molecules employing the many-electron eigenstates of constituent atoms in spectral-product forms. The approach provides a universal atomic-product description of the electronic structure of matter as an alternative to more commonly employed valence-bond- or molecular-orbital-based representations. The Hamiltonian matrix in this representation is seen to comprise a sum over atomic energies and a pairwise sum over Coulombic interaction terms that depend only on the separations of the individual atomic pairs. Overall electron antisymmetry can be enforced by unitary transformation when appropriate, rather than as a possibly encumbering or unnecessary global constraint. The matrix representative of the antisymmetrizer in the spectral-product basis, which is equivalent to the metric matrix of the corresponding explicitly antisymmetric basis, provides the required transformation to antisymmetric or linearly independent states after Hamiltonian evaluation. Particular attention is focused in the present report on properties of the metric matrix and on the atomic-product compositions of molecular eigenstates as described in the spectral-product representations. Illustrative calculations are reported for simple but prototypically important diatomic (H(2), CH) and triatomic (H(3), CH(2)) molecules employing algorithms and computer codes devised recently for this purpose. This particular implementation of the approach combines Slater-orbital-based one- and two-electron integral evaluations, valence-bond constructions of standard tableau functions and matrices, and transformations to atomic eigenstate-product representations. The calculated metric matrices and corresponding potential energy surfaces obtained in this way elucidate a number of aspects of the spectral-product development, including the nature of closure in the representation, the general redundancy or

  11. Penalized differential pathway analysis of integrative oncogenomics studies.

    PubMed

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

    2014-04-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.

  12. Integrated corridor management : phase I, concept development and foundational research. Task 3.4, identify integrated corridor management institutional strategies and administration

    DOT National Transportation Integrated Search

    2006-04-12

    Task 3 involves overall foundational research to further the understanding of various aspects of Integrated Corridor Management (ICM) and to identify integration issues needed to evaluate the feasibility of the ICM initiative. The focus of Task 3.4 a...

  13. New aspects of molecular imaging in prostate cancer.

    PubMed

    Ceci, Francesco; Castellucci, Paolo; Cerci, Juliano J; Fanti, Stefano

    2017-11-01

    Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging. PSMA, the glutamate carboxypeptidase II, is a membrane bound metallo-peptidase over-expressed in PCa cells. It has been shown that PSMA based imaging offers higher tumor detection rate compared to choline PET/CT and radiological conventional imaging, especially at very low PSA levels during biochemical recurrence. In addition PSMA, as theranostics agent, allows both radiolabeling with diagnostic (e.g. 68Ga, 18F) or therapeutic nuclides (e.g. 177Lu, 225Ac). Initial results show that PSMA-targeted radioligand therapy can potentially delay disease progression in metastatic castrate-resistant PCa. Despite still investigational, the bombesin-based radiotracers and antagonist of gastrin releasing-peptide receptor (GRP) (RM2) and anti1-amino-3-18Ffluorocyclobutane-1-carboxylic acid (18F-FACBC) are emerging as possible alternatives for investigating PCa. Considering the wide diffusion of PCa in the Europe and the United States, the presence of these new diagnostic techniques able to detect the disease with high sensitivity and specificity might have a clinical impact on the management of patients. PET/CT imaging with new radiopharmaceuticals can implement the patient management identifying lesion(s) not detectable with conventional imaging procedures. In this review article will be discussed the most promising new PET radiopharmaceuticals (68Ga-PSMA-11, 18F-FACBC, 68Ga-RM2) available at the moment, focusing the attention on their accuracy and their impact on

  14. Retroviral DNA Integration

    PubMed Central

    2016-01-01

    The integration of a DNA copy of the viral RNA genome into host chromatin is the defining step of retroviral replication. This enzymatic process is catalyzed by the virus-encoded integrase protein, which is conserved among retroviruses and LTR-retrotransposons. Retroviral integration proceeds via two integrase activities: 3′-processing of the viral DNA ends, followed by the strand transfer of the processed ends into host cell chromosomal DNA. Herein we review the molecular mechanism of retroviral DNA integration, with an emphasis on reaction chemistries and architectures of the nucleoprotein complexes involved. We additionally discuss the latest advances on anti-integrase drug development for the treatment of AIDS and the utility of integrating retroviral vectors in gene therapy applications. PMID:27198982

  15. Emerging molecular phenotypes of asthma

    PubMed Central

    Ray, Anuradha; Oriss, Timothy B.

    2014-01-01

    Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease. PMID:25326577

  16. Electronic Spectra from Molecular Dynamics: A Simple Approach.

    DTIC Science & Technology

    1983-10-01

    82.30.Cr. 33.20K. S2.40.1s The authors provided phototypeset copy for this paper using REFER TlL EON, TOFF On UNIX I ELECTRONIC SPECTRA FROM MOLECULAR...Alamos National Laboratory Los Alamos, NM 87545 I. INTRODUCTION In this paper we show how molecular dynamics can be used in a simple manner to com...could equally use Monte Carlo or explicit integration over coordinates to compute equilibrium electronic absorption bands. How- ever, molecular

  17. Molecular Aspects of Thyroid Hormone Actions

    PubMed Central

    Cheng, Sheue-Yann; Leonard, Jack L.; Davis, Paul J.

    2010-01-01

    Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological activities of T3 via transcriptional regulation. Two TR genes, α and β, encode four T3-binding receptor isoforms (α1, β1, β2, and β3). The transcriptional activity of TRs is regulated at multiple levels. Besides being regulated by T3, transcriptional activity is regulated by the type of thyroid hormone response elements located on the promoters of T3 target genes, by the developmental- and tissue-dependent expression of TR isoforms, and by a host of nuclear coregulatory proteins. These nuclear coregulatory proteins modulate the transcription activity of TRs in a T3-dependent manner. In the absence of T3, corepressors act to repress the basal transcriptional activity, whereas in the presence of T3, coactivators function to activate transcription. The critical role of TRs is evident in that mutations of the TRβ gene cause resistance to thyroid hormones to exhibit an array of symptoms due to decreasing the sensitivity of target tissues to T3. Genetically engineered knockin mouse models also reveal that mutations of the TRs could lead to other abnormalities beyond resistance to thyroid hormones, including thyroid cancer, pituitary tumors, dwarfism, and metabolic abnormalities. Thus, the deleterious effects of mutations of TRs are more severe than previously envisioned. These genetic-engineered mouse models provide valuable tools to ascertain further the molecular actions of unliganded TRs in vivo that could underlie the pathogenesis of hypothyroidism. Actions of thyroid hormone that are not initiated by liganding of the hormone to intranuclear TR are termed nongenomic. They may begin at the plasma membrane or in cytoplasm. Plasma membrane-initiated actions begin at a receptor on integrin αvβ3 that activates ERK1/2 and culminate in local membrane actions on

  18. 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.

  19. Molecular electronics: Some views on transport junctions and beyond

    PubMed Central

    Joachim, Christian; Ratner, Mark A.

    2005-01-01

    The field of molecular electronics comprises a fundamental set of issues concerning the electronic response of molecules as parts of a mesoscopic structure and a technology-facing area of science. We will overview some important aspects of these subfields. The most advanced ideas in the field involve the use of molecules as individual logic or memory units and are broadly based on using the quantum state space of the molecule. Current work in molecular electronics usually addresses molecular junction transport, where the molecule acts as a barrier for incoming electrons: This is the fundamental Landauer idea of “conduction as scattering” generalized to molecular junction structures. Another point of view in terms of superexchange as a guiding mechanism for coherent electron transfer through the molecular bridge is discussed. Molecules generally exhibit relatively strong vibronic coupling. The last section of this overview focuses on vibronic effects, including inelastic electron tunneling spectroscopy, hysteresis in junction charge transport, and negative differential resistance in molecular transport junctions. PMID:15956192

  20. Molecular electronics: some views on transport junctions and beyond.

    PubMed

    Joachim, Christian; Ratner, Mark A

    2005-06-21

    The field of molecular electronics comprises a fundamental set of issues concerning the electronic response of molecules as parts of a mesoscopic structure and a technology-facing area of science. We will overview some important aspects of these subfields. The most advanced ideas in the field involve the use of molecules as individual logic or memory units and are broadly based on using the quantum state space of the molecule. Current work in molecular electronics usually addresses molecular junction transport, where the molecule acts as a barrier for incoming electrons: This is the fundamental Landauer idea of "conduction as scattering" generalized to molecular junction structures. Another point of view in terms of superexchange as a guiding mechanism for coherent electron transfer through the molecular bridge is discussed. Molecules generally exhibit relatively strong vibronic coupling. The last section of this overview focuses on vibronic effects, including inelastic electron tunneling spectroscopy, hysteresis in junction charge transport, and negative differential resistance in molecular transport junctions.

  1. Peltier cooling in molecular junctions

    NASA Astrophysics Data System (ADS)

    Cui, Longji; Miao, Ruijiao; Wang, Kun; Thompson, Dakotah; Zotti, Linda Angela; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod

    2018-02-01

    The study of thermoelectricity in molecular junctions is of fundamental interest for the development of various technologies including cooling (refrigeration) and heat-to-electricity conversion1-4. Recent experimental progress in probing the thermopower (Seebeck effect) of molecular junctions5-9 has enabled studies of the relationship between thermoelectricity and molecular structure10,11. However, observations of Peltier cooling in molecular junctions—a critical step for establishing molecular-based refrigeration—have remained inaccessible. Here, we report direct experimental observations of Peltier cooling in molecular junctions. By integrating conducting-probe atomic force microscopy12,13 with custom-fabricated picowatt-resolution calorimetric microdevices, we created an experimental platform that enables the unified characterization of electrical, thermoelectric and energy dissipation characteristics of molecular junctions. Using this platform, we studied gold junctions with prototypical molecules (Au-biphenyl-4,4'-dithiol-Au, Au-terphenyl-4,4''-dithiol-Au and Au-4,4'-bipyridine-Au) and revealed the relationship between heating or cooling and charge transmission characteristics. Our experimental conclusions are supported by self-energy-corrected density functional theory calculations. We expect these advances to stimulate studies of both thermal and thermoelectric transport in molecular junctions where the possibility of extraordinarily efficient energy conversion has been theoretically predicted2-4,14.

  2. Integrating multiple evidences in taxonomy: species diversity and phylogeny of mustached bats (Mormoopidae: Pteronotus).

    PubMed

    Pavan, Ana Carolina; Marroig, Gabriel

    2016-10-01

    A phylogenetic systematic perspective is instrumental in recovering new species and their evolutionary relationships. The advent of new technologies for molecular and morphological data acquisition and analysis, allied to the integration of knowledge from different areas, such as ecology and population genetics, allows for the emergence of more rigorous, accurate and complete scientific hypothesis on species diversity. Mustached bats (genus Pteronotus) are a good model for the application of this integrative approach. They are a widely distributed and a morphologically homogeneous group, but comprising species with remarkable differences in their echolocation strategy and feeding behavior. The latest systematic review suggested six species with 17 subspecies in Pteronotus. Subsequent studies using discrete morphological characters supported the same arrangement. However, recent papers reported high levels of genetic divergence among conspecific taxa followed by bioacoustic and geographic agreement, suggesting an underestimated diversity in the genus. To date, no study merging genetic evidences and morphometric variation along the entire geographic range of this group has been attempted. Based on a comprehensive sampling including representatives of all current taxonomic units, we attempt to delimit species in Pteronotus through the application of multiple methodologies and hierarchically distinct datasets. The molecular approach includes six molecular markers from three genetic transmission systems; morphological investigations used 41 euclidean distances estimated through three-dimensional landmarks collected from 1628 skulls. The phylogenetic analysis reveals a greater diversity than previously reported, with a high correspondence among the genetic lineages and the currently recognized subspecies in the genus. Discriminant analysis of variables describing size and shape of cranial bones support the rising of the genetic groups to the specific status. Based on

  3. SSU rDNA divergence in planktonic foraminifera: molecular taxonomy and biogeographic implications.

    PubMed

    André, Aurore; Quillévéré, Frédéric; Morard, Raphaël; Ujiié, Yurika; Escarguel, Gilles; de Vargas, Colomban; de Garidel-Thoron, Thibault; Douady, Christophe J

    2014-01-01

    The use of planktonic foraminifera in paleoceanography requires taxonomic consistency and precise assessment of the species biogeography. Yet, ribosomal small subunit (SSUr) DNA analyses have revealed that most of the modern morpho-species of planktonic foraminifera are composed of a complex of several distinct genetic types that may correspond to cryptic or pseudo-cryptic species. These genetic types are usually delimitated using partial sequences located at the 3'end of the SSUrDNA, but typically based on empirical delimitation. Here, we first use patristic genetic distances calculated within and among genetic types of the most common morpho-species to show that intra-type and inter-type genetic distances within morpho-species may significantly overlap, suggesting that genetic types have been sometimes inconsistently defined. We further apply two quantitative and independent methods, ABGD (Automatic Barcode Gap Detection) and GMYC (General Mixed Yule Coalescent) to a dataset of published and newly obtained partial SSU rDNA for a more objective assessment of the species status of these genetic types. Results of these complementary approaches are highly congruent and lead to a molecular taxonomy that ranks 49 genetic types of planktonic foraminifera as genuine (pseudo)cryptic species. Our results advocate for a standardized sequencing procedure allowing homogenous delimitations of (pseudo)cryptic species. On the ground of this revised taxonomic framework, we finally provide an integrative taxonomy synthesizing geographic, ecological and morphological differentiations that can occur among the genuine (pseudo)cryptic species. Due to molecular, environmental or morphological data scarcities, many aspects of our proposed integrative taxonomy are not yet fully resolved. On the other hand, our study opens up the potential for a correct interpretation of environmental sequence datasets.

  4. SSU rDNA Divergence in Planktonic Foraminifera: Molecular Taxonomy and Biogeographic Implications

    PubMed Central

    André, Aurore; Quillévéré, Frédéric; Morard, Raphaël; Ujiié, Yurika; Escarguel, Gilles; de Vargas, Colomban; de Garidel-Thoron, Thibault; Douady, Christophe J.

    2014-01-01

    The use of planktonic foraminifera in paleoceanography requires taxonomic consistency and precise assessment of the species biogeography. Yet, ribosomal small subunit (SSUr) DNA analyses have revealed that most of the modern morpho-species of planktonic foraminifera are composed of a complex of several distinct genetic types that may correspond to cryptic or pseudo-cryptic species. These genetic types are usually delimitated using partial sequences located at the 3′end of the SSUrDNA, but typically based on empirical delimitation. Here, we first use patristic genetic distances calculated within and among genetic types of the most common morpho-species to show that intra-type and inter-type genetic distances within morpho-species may significantly overlap, suggesting that genetic types have been sometimes inconsistently defined. We further apply two quantitative and independent methods, ABGD (Automatic Barcode Gap Detection) and GMYC (General Mixed Yule Coalescent) to a dataset of published and newly obtained partial SSU rDNA for a more objective assessment of the species status of these genetic types. Results of these complementary approaches are highly congruent and lead to a molecular taxonomy that ranks 49 genetic types of planktonic foraminifera as genuine (pseudo)cryptic species. Our results advocate for a standardized sequencing procedure allowing homogenous delimitations of (pseudo)cryptic species. On the ground of this revised taxonomic framework, we finally provide an integrative taxonomy synthesizing geographic, ecological and morphological differentiations that can occur among the genuine (pseudo)cryptic species. Due to molecular, environmental or morphological data scarcities, many aspects of our proposed integrative taxonomy are not yet fully resolved. On the other hand, our study opens up the potential for a correct interpretation of environmental sequence datasets. PMID:25119900

  5. Harnessing Reversible Electronic Energy Transfer: From Molecular Dyads to Molecular Machines.

    PubMed

    Denisov, Sergey A; Yu, Shinlin; Pozzo, Jean-Luc; Jonusauskas, Gediminas; McClenaghan, Nathan D

    2016-06-17

    Reversible electronic energy transfer (REET) may be instilled in bi-/multichromophoric molecule-based systems, following photoexcitation, upon judicious structural integration of matched chromophores. This leads to a new set of photophysical properties for the ensemble, which can be fully characterized by steady-state and time-resolved spectroscopic methods. Herein, we take a comprehensive look at progress in the development of this type of supermolecule in the last five years, which has seen systems evolve from covalently tethered dyads to synthetic molecular machines, exemplified by two different pseudorotaxanes. Indeed, REET holds promise in the control of movement in molecular machines, their assembly/disassembly, as well as in charge separation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Next generation extended Lagrangian first principles molecular dynamics

    NASA Astrophysics Data System (ADS)

    Niklasson, Anders M. N.

    2017-08-01

    Extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] is formulated for general Hohenberg-Kohn density-functional theory and compared with the extended Lagrangian framework of first principles molecular dynamics by Car and Parrinello [Phys. Rev. Lett. 55, 2471 (1985)]. It is shown how extended Lagrangian Born-Oppenheimer molecular dynamics overcomes several shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while improving or maintaining important features of Car-Parrinello simulations. The accuracy of the electronic degrees of freedom in extended Lagrangian Born-Oppenheimer molecular dynamics, with respect to the exact Born-Oppenheimer solution, is of second-order in the size of the integration time step and of fourth order in the potential energy surface. Improved stability over recent formulations of extended Lagrangian Born-Oppenheimer molecular dynamics is achieved by generalizing the theory to finite temperature ensembles, using fractional occupation numbers in the calculation of the inner-product kernel of the extended harmonic oscillator that appears as a preconditioner in the electronic equations of motion. Material systems that normally exhibit slow self-consistent field convergence can be simulated using integration time steps of the same order as in direct Born-Oppenheimer molecular dynamics, but without the requirement of an iterative, non-linear electronic ground-state optimization prior to the force evaluations and without a systematic drift in the total energy. In combination with proposed low-rank and on the fly updates of the kernel, this formulation provides an efficient and general framework for quantum-based Born-Oppenheimer molecular dynamics simulations.

  7. Next generation extended Lagrangian first principles molecular dynamics.

    PubMed

    Niklasson, Anders M N

    2017-08-07

    Extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] is formulated for general Hohenberg-Kohn density-functional theory and compared with the extended Lagrangian framework of first principles molecular dynamics by Car and Parrinello [Phys. Rev. Lett. 55, 2471 (1985)]. It is shown how extended Lagrangian Born-Oppenheimer molecular dynamics overcomes several shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while improving or maintaining important features of Car-Parrinello simulations. The accuracy of the electronic degrees of freedom in extended Lagrangian Born-Oppenheimer molecular dynamics, with respect to the exact Born-Oppenheimer solution, is of second-order in the size of the integration time step and of fourth order in the potential energy surface. Improved stability over recent formulations of extended Lagrangian Born-Oppenheimer molecular dynamics is achieved by generalizing the theory to finite temperature ensembles, using fractional occupation numbers in the calculation of the inner-product kernel of the extended harmonic oscillator that appears as a preconditioner in the electronic equations of motion. Material systems that normally exhibit slow self-consistent field convergence can be simulated using integration time steps of the same order as in direct Born-Oppenheimer molecular dynamics, but without the requirement of an iterative, non-linear electronic ground-state optimization prior to the force evaluations and without a systematic drift in the total energy. In combination with proposed low-rank and on the fly updates of the kernel, this formulation provides an efficient and general framework for quantum-based Born-Oppenheimer molecular dynamics simulations.

  8. Insights into the molecular aspects of neuroprotective Bacoside A and Bacopaside I.

    PubMed

    Sekhar, Vini C; Viswanathan, Gayathri; Baby, Sabulal

    2018-04-19

    Bacopa monnieri, commonly known as Brahmi, has been extensively used as a neuromedicine for various disorders such as anxiety, depression and memory loss. Chemical characterization studies revealed the major active constituents of the herb as the triterpenoid saponins, bacosides. Bacoside A, the vital neuroprotective constituent, is composed of four constituents viz., bacoside A3, bacopaside II, jujubogenin isomer of bacopasaponin C (bacopaside X) and bacopasaponin C. B. monnieri extracts as well as bacosides successfully establish a healthy antioxidant environment in various tissues especially in liver and brain. Free radical scavenging, suppression of lipid peroxidation and activation of antioxidant enzymes by bacosides help to attain a physiological state of minimized oxidative stress. The molecular basis of neuroprotective activity of bacosides is attributed to the regulation of mRNA translation and surface expression of neuroreceptors such as AMPAR, NMDAR and GABAR in the various parts of the brain. Bioavailability as well as binding of neuroprotective agents (such as bacosides) to these receptors is controlled by the Blood Brain Barrier (BBB). However, nano conversion of these drug candidates easily resolves the BBB restriction and carries a promising role in future therapies. This review summarizes the neuroprotective functions of the B. monnieri extracts as well as its active compounds (bacoside A, bacopaside I) and the molecular mechanisms responsible for these pharmacological activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. In search of the Golden Fleece: Unraveling principles of morphogenesis by studying the integrative biology of skin appendages

    PubMed Central

    Hughes, Michael W.; Wu, Ping; Jiang, Ting-Xin; Lin, Sung-Jan; Dong, Chen-Yuan; Li, Ang; Hsieh, Fon-Jou; Widelitz, Randall B.; Choung, Cheng Ming

    2013-01-01

    Summary The mythological story of the Golden Fleece symbolizes the magical regenerative power of skin appendages. Similar to the adventurous pursuit of the Golden Fleece by the multi-talented Argonauts, today we also need an integrated multi-disciplined approach to understand the cellular and molecular processes during development, regeneration and evolution of skin appendages. To this end, we have explored several aspects of skin appendage biology that contribute to the Turing activator / inhibitor model in feather pattern formation, the topo-biological arrangement of stem cells in organ shape determination, the macro-environmental regulation of stem cells in regenerative hair waves, and potential novel molecular pathways in the morphological evolution of feathers. Here we show our current integrative biology efforts to unravel the complex cellular behavior in patterning stem cells and the control of regional specificity in skin appendages. We use feather / scale tissue recombination to demonstrate the timing control of competence and inducibility. Feathers from different body regions are used to study skin regional specificity. Bioinformatic analyses of transcriptome microarrays show the potential involvement of candidate molecular pathways. We further show Hox genes exhibit some region specific expression patterns. To visualize real time events, we applied time-lapse movies, confocal microscopy and multiphoton microscopy to analyze the morphogenesis of cultured embryonic chicken skin explants. These modern imaging technologies reveal unexpectedly complex cellular flow and organization of extracellular matrix molecules in three dimensions. While these approaches are in preliminary stages, this perspective highlights the challenges we face and new integrative tools we will use. Future work will follow these leads to develop a systems biology view and understanding in the morphogenetic principles that govern the development and regeneration of ectodermal organs

  10. Singlet molecular oxygen generated by biological hydroperoxides.

    PubMed

    Miyamoto, Sayuri; Martinez, Glaucia R; Medeiros, Marisa H G; Di Mascio, Paolo

    2014-10-05

    The chemistry behind the phenomenon of ultra-weak photon emission has been subject of considerable interest for decades. Great progress has been made on the understanding of the chemical generation of electronically excited states that are involved in these processes. Proposed mechanisms implicated the production of excited carbonyl species and singlet molecular oxygen in the mechanism of generation of chemiluminescence in biological system. In particular, attention has been focused on the potential generation of singlet molecular oxygen in the recombination reaction of peroxyl radicals by the Russell mechanism. In the last ten years, our group has demonstrated the generation of singlet molecular oxygen from reactions involving the decomposition of biologically relevant hydroperoxides, especially from lipid hydroperoxides in the presence of metal ions, peroxynitrite, HOCl and cytochrome c. In this review we will discuss details on the chemical aspects related to the mechanism of singlet molecular oxygen generation from different biological hydroperoxides. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Identification of a New Mullet Species Complex Based on an Integrative Molecular and Cytogenetic Investigation of Mugil hospes (Mugilidae: Mugiliformes).

    PubMed

    Nirchio, Mauro; Paim, Fabilene G; Milana, Valentina; Rossi, Anna R; Oliveira, Claudio

    2018-01-01

    Mullets are very common fishes included in the family Mugilidae, (Mugiliformes), which are characterized by both a remarkably uniform external morphology and internal anatomy. Recently, within this family, different species complexes were molecularly identified within Mugil , a genus which is characterized by lineages that sometimes show very different karyotypes. Here we report the results of cytogenetic and molecular analyses conducted on Mugil hospes , commonly known as the hospe mullet, from Ecuador. The study aims to verify whether the original described species from the Pacific Ocean corresponds to that identified in the Atlantic Ocean, and to identify species-specific chromosome markers that can add new comparative data about Mugilidae karyotype evolution. The karyotype of M. hospes from Ecuador is composed of 48 acrocentric chromosomes and shows two active nucleolar organizer regions (NORs). In situ hybridization, using different types of repetitive sequences (rDNAs, U1 snDNA, telomeric repeats) as probes, identified species-specific chromosome markers that have been compared with those of other species of the genus Mugil . Cytochrome c oxidase subunit I (COI) sequence analysis shows only 92-93% similarity with sequences previously deposited under this species name in GenBank, all of which were from the Atlantic Ocean. Phylogenetic reconstructions indicate the presence of three well-supported hospe mullet lineages whose molecular divergence is compatible with the presence of distinct species. Indeed, the first lineage includes samples from Ecuador, whereas the other two lineages include the Atlantic samples and correspond to M. brevirostris from Brazil and Mugil sp. R from Belize/Venezuela. Results here provided reiterate the pivotal importance of an integrative molecular and cytogenetic approach in the reconstruction of the relationships within Mugilidae.

  12. Identification of a New Mullet Species Complex Based on an Integrative Molecular and Cytogenetic Investigation of Mugil hospes (Mugilidae: Mugiliformes)

    PubMed Central

    Nirchio, Mauro; Paim, Fabilene G.; Milana, Valentina; Rossi, Anna R.; Oliveira, Claudio

    2018-01-01

    Mullets are very common fishes included in the family Mugilidae, (Mugiliformes), which are characterized by both a remarkably uniform external morphology and internal anatomy. Recently, within this family, different species complexes were molecularly identified within Mugil, a genus which is characterized by lineages that sometimes show very different karyotypes. Here we report the results of cytogenetic and molecular analyses conducted on Mugil hospes, commonly known as the hospe mullet, from Ecuador. The study aims to verify whether the original described species from the Pacific Ocean corresponds to that identified in the Atlantic Ocean, and to identify species-specific chromosome markers that can add new comparative data about Mugilidae karyotype evolution. The karyotype of M. hospes from Ecuador is composed of 48 acrocentric chromosomes and shows two active nucleolar organizer regions (NORs). In situ hybridization, using different types of repetitive sequences (rDNAs, U1 snDNA, telomeric repeats) as probes, identified species-specific chromosome markers that have been compared with those of other species of the genus Mugil. Cytochrome c oxidase subunit I (COI) sequence analysis shows only 92–93% similarity with sequences previously deposited under this species name in GenBank, all of which were from the Atlantic Ocean. Phylogenetic reconstructions indicate the presence of three well-supported hospe mullet lineages whose molecular divergence is compatible with the presence of distinct species. Indeed, the first lineage includes samples from Ecuador, whereas the other two lineages include the Atlantic samples and correspond to M. brevirostris from Brazil and Mugil sp. R from Belize/Venezuela. Results here provided reiterate the pivotal importance of an integrative molecular and cytogenetic approach in the reconstruction of the relationships within Mugilidae. PMID:29459882

  13. Clinical, molecular genetics and therapeutic aspects of syndromic obesity.

    PubMed

    Geets, E; Meuwissen, M E C; Van Hul, W

    2018-04-26

    Obesity has become a major health problem worldwide. To date, more than 25 different syndromic forms of obesity are known in which one (monogenic) or multiple (polygenic) genes are involved. This review gives an overview of these forms and focuses more in detail on six syndromes: Prader Willi Syndrome and Prader Willi like phenotype, Bardet Biedl Syndrome, Alström Syndrome, Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation syndrome and 16p11.2 (micro)deletions. Years of research provided plenty of information on the molecular genetics of these disorders and the obesity phenotype leading to a more individualized treatment of the symptoms, however, a lot of questions still remain unanswered. As these obesity syndromes have different signs and symptoms in common, it makes it difficult to accurately diagnose patients which may result in inappropriate treatment of the disease. Therefore, the big challenge for clinicians and scientists is to more clearly differentiate all syndromic forms of obesity to provide conclusive genetic explanations and eventually deliver accurate genetic counseling and treatment. In addition, further delineation of the (functions of the) underlying genes with the use of array- or next generation sequencing-based technology will be helpful to unravel the mechanisms of energy metabolism in the general population. This article is protected by copyright. All rights reserved.

  14. Research Integrity of Individual Scientist

    NASA Astrophysics Data System (ADS)

    Haklak, Rockbill

    We are discussing about many aspects of research integrity of individual scientist, who faces the globalization of research ethics in the traditional culture and custom of Japan. Topics are scientific misconduct (fabrication, falsification, and plagiarism) in writing paper and presenting research results. Managements of research material, research record, grant money, authorship, and conflict of interest are also analyzed and discussed. Finally, we make 5 recommendations to improve research integrity in Japan.

  15. Simulation and understanding of atomic and molecular quantum crystals

    NASA Astrophysics Data System (ADS)

    Cazorla, Claudio; Boronat, Jordi

    2017-07-01

    Quantum crystals abound in the whole range of solid-state species. Below a certain threshold temperature the physical behavior of rare gases (He 4 and Ne), molecular solids (H2 and CH4 ), and some ionic (LiH), covalent (graphite), and metallic (Li) crystals can be explained only in terms of quantum nuclear effects (QNE). A detailed comprehension of the nature of quantum solids is critical for achieving progress in a number of fundamental and applied scientific fields such as planetary sciences, hydrogen storage, nuclear energy, quantum computing, and nanoelectronics. This review describes the current physical understanding of quantum crystals formed by atoms and small molecules, as well as the wide palette of simulation techniques that are used to investigate them. Relevant aspects in these materials such as phase transformations, structural properties, elasticity, crystalline defects, and the effects of reduced dimensionality are discussed thoroughly. An introduction to quantum Monte Carlo techniques, which in the present context are the simulation methods of choice, and other quantum simulation approaches (e.g., path-integral molecular dynamics and quantum thermal baths) is provided. The overarching objective of this article is twofold: first, to clarify in which crystals and physical situations the disregard of QNE may incur in important bias and erroneous interpretations. And second, to promote the study and appreciation of QNE, a topic that traditionally has been treated in the context of condensed matter physics, within the broad and interdisciplinary areas of materials science.

  16. An Integrative Platform for Three-dimensional Quantitative Analysis of Spatially Heterogeneous Metastasis Landscapes

    NASA Astrophysics Data System (ADS)

    Guldner, Ian H.; Yang, Lin; Cowdrick, Kyle R.; Wang, Qingfei; Alvarez Barrios, Wendy V.; Zellmer, Victoria R.; Zhang, Yizhe; Host, Misha; Liu, Fang; Chen, Danny Z.; Zhang, Siyuan

    2016-04-01

    Metastatic microenvironments are spatially and compositionally heterogeneous. This seemingly stochastic heterogeneity provides researchers great challenges in elucidating factors that determine metastatic outgrowth. Herein, we develop and implement an integrative platform that will enable researchers to obtain novel insights from intricate metastatic landscapes. Our two-segment platform begins with whole tissue clearing, staining, and imaging to globally delineate metastatic landscape heterogeneity with spatial and molecular resolution. The second segment of our platform applies our custom-developed SMART 3D (Spatial filtering-based background removal and Multi-chAnnel forest classifiers-based 3D ReconsTruction), a multi-faceted image analysis pipeline, permitting quantitative interrogation of functional implications of heterogeneous metastatic landscape constituents, from subcellular features to multicellular structures, within our large three-dimensional (3D) image datasets. Coupling whole tissue imaging of brain metastasis animal models with SMART 3D, we demonstrate the capability of our integrative pipeline to reveal and quantify volumetric and spatial aspects of brain metastasis landscapes, including diverse tumor morphology, heterogeneous proliferative indices, metastasis-associated astrogliosis, and vasculature spatial distribution. Collectively, our study demonstrates the utility of our novel integrative platform to reveal and quantify the global spatial and volumetric characteristics of the 3D metastatic landscape with unparalleled accuracy, opening new opportunities for unbiased investigation of novel biological phenomena in situ.

  17. The UIST image slicing integral field unit

    NASA Astrophysics Data System (ADS)

    Ramsay Howat, S.; Todd, S.; Wells, M.; Hastings, P.

    2006-06-01

    The UKIRT Imager Spectrometer (UIST) contains a deployable integral field unit which is one of the most popular modes of this common-user instrument. In this paper, we review all aspects of the UIST IFU from the design and production of the aluminium mirrors to the integration with the telescope system during commissioning. Reduction of the integral field data is fully supported by the UKIRT data reduction pipeline, ORAC-DR.

  18. Towards a more molecular taxonomy of disease.

    PubMed

    Park, Jisoo; Hescott, Benjamin J; Slonim, Donna K

    2017-07-27

    Disease taxonomies have been designed for many applications, but they tend not to fully incorporate the growing amount of molecular-level knowledge of disease processes, inhibiting research efforts. Understanding the degree to which we can infer disease relationships from molecular data alone may yield insights into how to ultimately construct more modern taxonomies that integrate both physiological and molecular information. We introduce a new technique we call Parent Promotion to infer hierarchical relationships between disease terms using disease-gene data. We compare this technique with both an established ontology inference method (CliXO) and a minimum weight spanning tree approach. Because there is no gold standard molecular disease taxonomy available, we compare our inferred hierarchies to both the Medical Subject Headings (MeSH) category C forest of diseases and to subnetworks of the Disease Ontology (DO). This comparison provides insights about the inference algorithms, choices of evaluation metrics, and the existing molecular content of various subnetworks of MeSH and the DO. Our results suggest that the Parent Promotion method performs well in most cases. Performance across MeSH trees is also correlated between inference methods. Specifically, inferred relationships are more consistent with those in smaller MeSH disease trees than larger ones, but there are some notable exceptions that may correlate with higher molecular content in MeSH. Our experiments provide insights about learning relationships between diseases from disease genes alone. Future work should explore the prospect of disease term discovery from molecular data and how best to integrate molecular data with anatomical and clinical knowledge. This study nonetheless suggests that disease gene information has the potential to form an important part of the foundation for future representations of the disease landscape.

  19. Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations.

    PubMed

    Bottaro, Sandro; Bussi, Giovanni; Kennedy, Scott D; Turner, Douglas H; Lindorff-Larsen, Kresten

    2018-05-01

    RNA molecules are key players in numerous cellular processes and are characterized by a complex relationship between structure, dynamics, and function. Despite their apparent simplicity, RNA oligonucleotides are very flexible molecules, and understanding their internal dynamics is particularly challenging using experimental data alone. We show how to reconstruct the conformational ensemble of four RNA tetranucleotides by combining atomistic molecular dynamics simulations with nuclear magnetic resonance spectroscopy data. The goal is achieved by reweighting simulations using a maximum entropy/Bayesian approach. In this way, we overcome problems of current simulation methods, as well as in interpreting ensemble- and time-averaged experimental data. We determine the populations of different conformational states by considering several nuclear magnetic resonance parameters and point toward properties that are not captured by state-of-the-art molecular force fields. Although our approach is applied on a set of model systems, it is fully general and may be used to study the conformational dynamics of flexible biomolecules and to detect inaccuracies in molecular dynamics force fields.

  20. Integrated biochemical, molecular genetic, and bioacoustical analysis of mesoscale variability of the euphausiid Nematoscelis difficilis in the California Current

    NASA Astrophysics Data System (ADS)

    Bucklin, Ann; Wiebe, Peter H.; Smolenack, Sara B.; Copley, Nancy J.; Clarke, M. Elizabeth

    2002-03-01

    Integrated assessment of the euphausiid Nematoscelis difficilis (Crustacea; Euphausiacea) and the zooplankton assemblage of the California Current was designed to investigate individual, population, and community responses to mesoscale variability in biological and physical characters of the ocean. Zooplankton samples and observational data were collected along a cross-shelf transect of the California Current in association with the California Cooperative Fisheries Investigations (CalCOFI) Survey during October 1996. The transect crossed three domains defined by temperature and salinity: nearshore, mid-Current, and offshore. Individual N. difficilis differed in physiological condition along the transect, with higher size-corrected concentrations of four central metabolic enzymes (citrate synthetase, hexokinase, lactate dehydrogenase (LDH), and phosphoglucose isomerase (PGI)) for euphausiids collected in nearshore waters than in mid-Current and offshore waters. There was little variation in the DNA sequences of the genes encoding PGI and LDH (all DNA changes were either silent or heterozygous base substitutions), suggesting that differences in enzyme concentration did not result from underlying molecular genetic variation. The population genetic makeup of N. difficilis varied from sample to sample based on haplotype frequencies of mitochondrial cytochrome oxidase I (mtCOI; P=0.029). There were significant differences between pooled nearshore and offshore samples, based on allele frequencies at two sites of common substitutions in the mtCOI sequence ( P=0.020 and 0.026). Silhouette and bioacoustical backscattering measurements of the zooplankton assemblage of the top 100 m showed marked diel vertical migration of the scattering layer, of which euphausiids were a small but significant fraction. The biochemical and molecular assays are used as indices of complex physiological (i.e., growth and condition) and genetic (i.e., mortality) processes; the bioacoustical

  1. EDITORIAL: Focus on Molecular Electronics FOCUS ON MOLECULAR ELECTRONICS

    NASA Astrophysics Data System (ADS)

    Scheer, Elke; Reineker, Peter

    2008-06-01

    The notion 'molecular electronics' has been used more frequently since the 1970s and summarizes a series of physical phenomena and ideas for their application in connection with organic molecules, oligomers, polymers, organic aggregates and solids. The properties studied in this field were connected to optical and electrical phenomena, such as optical absorption, fluorescence, nonlinear optics, energy transport, charge transfer, electrical conductance, and electron and nuclear spin-resonance. The final goal was and is to build devices which can compete or surpass some aspects of inorganic semiconductor devices. For example, on the basis of organic molecules there exist rectifiers, transistors, molecular wires, organic light emitting diodes, elements for photovoltaics, and displays. With respect to applications, one aspect of the organic materials is their broad variability and the lower effort and costs for their processability. The step from microstructures to the investigation of nanostructures is a big challenge also in this field and has lead to what nowadays is called molecular electronics in its narrow sense. In this field the subjects of the studies are often single molecules, e.g. single molecule optical spectroscopy, electrical conductance, i.e. charge transport through a single molecule, the influence of vibrational degrees of freedom, etc. A challenge here is to provide the techniques for addressing in a reproducible way the molecular scale. In another approach small molecular ensembles are studied in order to avoid artefacts from particular contact situations. The recent development of the field is presented in [1-8]. In this Focus Issue we present new results in the field of 'molecular electronics', both in its broad and specialized sense. One of the basic questions is the distribution of the energy levels responsible for optical absorption on the one hand and for the transport of charge on the other. A still unanswered question is whether the Wannier

  2. Fast computation of molecular random phase approximation correlation energies using resolution of the identity and imaginary frequency integration

    NASA Astrophysics Data System (ADS)

    Eshuis, Henk; Yarkony, Julian; Furche, Filipp

    2010-06-01

    The random phase approximation (RPA) is an increasingly popular post-Kohn-Sham correlation method, but its high computational cost has limited molecular applications to systems with few atoms. Here we present an efficient implementation of RPA correlation energies based on a combination of resolution of the identity (RI) and imaginary frequency integration techniques. We show that the RI approximation to four-index electron repulsion integrals leads to a variational upper bound to the exact RPA correlation energy if the Coulomb metric is used. Auxiliary basis sets optimized for second-order Møller-Plesset (MP2) calculations are well suitable for RPA, as is demonstrated for the HEAT [A. Tajti et al., J. Chem. Phys. 121, 11599 (2004)] and MOLEKEL [F. Weigend et al., Chem. Phys. Lett. 294, 143 (1998)] benchmark sets. Using imaginary frequency integration rather than diagonalization to compute the matrix square root necessary for RPA, evaluation of the RPA correlation energy requires O(N4 log N) operations and O(N3) storage only; the price for this dramatic improvement over existing algorithms is a numerical quadrature. We propose a numerical integration scheme that is exact in the two-orbital case and converges exponentially with the number of grid points. For most systems, 30-40 grid points yield μH accuracy in triple zeta basis sets, but much larger grids are necessary for small gap systems. The lowest-order approximation to the present method is a post-Kohn-Sham frequency-domain version of opposite-spin Laplace-transform RI-MP2 [J. Jung et al., Phys. Rev. B 70, 205107 (2004)]. Timings for polyacenes with up to 30 atoms show speed-ups of two orders of magnitude over previous implementations. The present approach makes it possible to routinely compute RPA correlation energies of systems well beyond 100 atoms, as is demonstrated for the octapeptide angiotensin II.

  3. Fast computation of molecular random phase approximation correlation energies using resolution of the identity and imaginary frequency integration.

    PubMed

    Eshuis, Henk; Yarkony, Julian; Furche, Filipp

    2010-06-21

    The random phase approximation (RPA) is an increasingly popular post-Kohn-Sham correlation method, but its high computational cost has limited molecular applications to systems with few atoms. Here we present an efficient implementation of RPA correlation energies based on a combination of resolution of the identity (RI) and imaginary frequency integration techniques. We show that the RI approximation to four-index electron repulsion integrals leads to a variational upper bound to the exact RPA correlation energy if the Coulomb metric is used. Auxiliary basis sets optimized for second-order Møller-Plesset (MP2) calculations are well suitable for RPA, as is demonstrated for the HEAT [A. Tajti et al., J. Chem. Phys. 121, 11599 (2004)] and MOLEKEL [F. Weigend et al., Chem. Phys. Lett. 294, 143 (1998)] benchmark sets. Using imaginary frequency integration rather than diagonalization to compute the matrix square root necessary for RPA, evaluation of the RPA correlation energy requires O(N(4) log N) operations and O(N(3)) storage only; the price for this dramatic improvement over existing algorithms is a numerical quadrature. We propose a numerical integration scheme that is exact in the two-orbital case and converges exponentially with the number of grid points. For most systems, 30-40 grid points yield muH accuracy in triple zeta basis sets, but much larger grids are necessary for small gap systems. The lowest-order approximation to the present method is a post-Kohn-Sham frequency-domain version of opposite-spin Laplace-transform RI-MP2 [J. Jung et al., Phys. Rev. B 70, 205107 (2004)]. Timings for polyacenes with up to 30 atoms show speed-ups of two orders of magnitude over previous implementations. The present approach makes it possible to routinely compute RPA correlation energies of systems well beyond 100 atoms, as is demonstrated for the octapeptide angiotensin II.

  4. Student Perspectives of the Integration of Faith and Learning in an Online Counselor Education Program: A Program Evaluation

    ERIC Educational Resources Information Center

    Van Wynsberg, Kevin

    2016-01-01

    The integration of faith and learning is a valued aspect of Christian education and holds particular importance in training professional counselors. Currently, literature related to integration learning has been limited to residential environments, and students' expectations and most valued aspects of learning integration have received little…

  5. Molecular layer interneurons of the cerebellum: developmental and morphological aspects.

    PubMed

    Sotelo, Constantino

    2015-10-01

    During the past 25 years, our knowledge on the development of basket and stellate cells (molecular layer interneurons [MLIs]) has completely changed, not only regarding their origin from the ventricular zone, corresponding to the primitive cerebellar neuroepithelium, instead of the external granular layer, but above all by providing an almost complete account of the genetic regulations (transcription factors and other genes) involved in their differentiation and synaptogenesis. Moreover, it has been shown that MLIs' precursors (dividing neuroblasts) and not young postmitotic neurons, as in other germinal neuroepithelia, leave the germinative zone and migrate all along a complex and lengthy path throughout the presumptive cerebellar white matter, which provides suitable niches exerting epigenetic influences on their ultimate neuronal identities. Recent studies carried out on the anatomical-functional properties of adult MLIs emphasize the importance of these interneurons in regulating PC inhibition, and point out the crucial role played by electrical synaptic transmission between MLIs as well as ephaptic interactions between them and Purkinje cells at the pinceaux level, in the regulation of this inhibition.

  6. Recent development of nanoparticles for molecular imaging

    NASA Astrophysics Data System (ADS)

    Kim, Jonghoon; Lee, Nohyun; Hyeon, Taeghwan

    2017-10-01

    Molecular imaging enables us to non-invasively visualize cellular functions and biological processes in living subjects, allowing accurate diagnosis of diseases at early stages. For successful molecular imaging, a suitable contrast agent with high sensitivity is required. To date, various nanoparticles have been developed as contrast agents for medical imaging modalities. In comparison with conventional probes, nanoparticles offer several advantages, including controllable physical properties, facile surface modification and long circulation time. In addition, they can be integrated with various combinations for multimodal imaging and therapy. In this opinion piece, we highlight recent advances and future perspectives of nanomaterials for molecular imaging. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  7. A molecular dynamics study of polymer/graphene interfacial systems

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

    Rissanou, Anastassia N.; Harmandaris, Vagelis

    2014-05-15

    Graphene based polymer nanocomposites are hybrid materials with a very broad range of technological applications. In this work, we study three hybrid polymer/graphene interfacial systems (polystyrene/graphene, poly(methyl methacrylate)/graphene and polyethylene/graphene) through detailed atomistic molecular dynamics (MD) simulations. Density profiles, structural characteristics and mobility aspects are being examined at the molecular level for all model systems. In addition, we compare the properties of the hybrid systems to the properties of the corresponding bulk ones, as well as to theoretical predictions.

  8. New epidemiological aspects of visceral and cutaneous leishmaniasis in Taza, Morocco.

    PubMed

    Hakkour, Maryam; Hmamouch, Asmae; El Alem, Mohamed Mahmoud; Rhalem, Abdelkbir; Amarir, Fatima; Touzani, Mohamed; Sadak, Abderrahim; Fellah, Hajiba; Sebti, Faiza

    2016-11-29

    Leishmaniasis is considered among the main endemic diseases in Morocco. However, further knowledge about epidemiological aspects of this disease is needed in several provinces to plan control and preventive strategies to tackle the disease. The present study aims to determine the epidemiological aspect of cutaneous and visceral leishmaniasis in Taza Province from 2007-2014 and to identify the circulating species in this province. The temporal study from 2007 to 2014 showed that the number of cutaneous leishmaniasis cases increased since 2010. During the period of study, most leishmaniasis cases were detected in both urban and rural areas with 34% of cases detected in two urban localities, Bab Zitouna and Bab tété with 297 and 106 cases, respectively. The molecular study of cutaneous leishmaniasis showed the presence of non-sporadic Leishmania infantum and Leishmania tropica in this province. Regarding visceral leishmaniasis, Leishmania infantum is the species that has been identified. The epidemio-molecular study of leishmaniasis in Taza Province showed the coexistence of two species of Leishmania in the same foci. They also indicated that CL due to Leishmania infantum is more prevalent than reported in the literature. These results will be helpful for the implementation of control strategies by targeting dogs that constitute a reservoir of Leishmania infantum.

  9. 2014 SRP Integration Transcript

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2014-01-01

    HRP's mission is to reduce the risks to human health and performance during long-duration spaceflight. The HRP Integrated Research Plan (IRP) contains the research plans for the 32 risks that require research to characterize and mitigate. From its inception the "integrate" aspect of the IRP has denoted the integrated nature of risks to human health and performance. Even though each risk in the IRP has its own research plan and is tracked separately, the interrelated nature of health and performance requires that they be addressed in an integrative or holistic fashion so that the connectedness of physiological systems within the human body and the integrated response to spaceflight can be addressed. Common characteristics of the spaceflight environment include altered gravity, atmospheres, and light/dark cycles; space radiation; isolation; noise; and periods of high or low workload. Long-term exposure to this unique environment produces a suite of physiological effects such as stress; vision, neurocognitive, and anthropometric changes; circadian misalignment; fluid shifts; cardiovascular deconditioning; immune dysregulation; and altered nutritional requirements. Expanding cross-disciplinary integrative approaches that synthesize concepts or data from two or more disciplines would improve the identification and characterization risk factors, and enable the development of countermeasures relevant to multiple risks. Cross-disciplinary approaches might also help to illuminate problem areas that may arise when a countermeasure adversely impacts risks other than those which it was developed to mitigate, or to identify groupings of physiological changes that are likely to occur that may impact the overall risk posture. In 2014 HRP embarked on a pilot study that combined four SRPs (and 12 HRP risks) - Behavioral Health, Sensorimotor, Cardiovascular, and Bone/Muscle - specifically to discuss cross-disciplinary integration. The points outlined below were suggested to seed the

  10. [Molecular aspects of human papillomaviruses and their relation to uterine cervix cancer].

    PubMed

    García-Carrancá, A; Gariglio, P V

    1993-01-01

    Papillomaviruses (wart viruses) are responsible for the development of benign and malignant epithelial lesions in mammals. More than 60 different types of human papillomaviruses (HPVs) have been isolated to date. Some of them are major candidates as etiologic agents in cervical cancer. DNA from HPV types 16, 18 and 33 is usually found integrated in about 90 percent of genital carcinomas. Integration of the viral DNA into the cellular genome may be an important step towards the development of malignancy. Two early genes of HPVs (E6 y E7) are involved in cellular transformation. Another early gene (E2) participates in gene control by directly binding to conserved DNA motifs in the viral genome. Several protein factors of viral and cellular origin interact with the regulatory region of HPVs and participate in the regulation transcription of oncogenes E6 and E7. Cellular factors, such as immune system and oncogene and anti-oncogene alterations, seem to play an important role in papillomavirus-associated cervical carcinogenesis.

  11. Clinical and molecular aspects of distal renal tubular acidosis in children.

    PubMed

    Besouw, Martine T P; Bienias, Marc; Walsh, Patrick; Kleta, Robert; Van't Hoff, William G; Ashton, Emma; Jenkins, Lucy; Bockenhauer, Detlef

    2017-06-01

    Distal renal tubular acidosis (dRTA) is characterized by hyperchloraemic metabolic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis. It is due to reduced urinary acidification by the α-intercalated cells in the collecting duct and can be caused by mutations in genes that encode subunits of the vacuolar H + -ATPase (ATP6V1B1, ATP6V0A4) or the anion exchanger 1 (SLC4A1). Treatment with alkali is the mainstay of therapy. This study is an analysis of clinical data from a long-term follow-up of 24 children with dRTA in a single centre, including a genetic analysis. Of the 24 children included in the study, genetic diagnosis was confirmed in 19 patients, with six children having mutations in ATP6V1B1, ten in ATP6V0A4 and three in SLC4A1; molecular diagnosis was not available for five children. Five novel mutations were detected (2 in ATP6V1B1 and 3 in ATP6V0A4). Two-thirds of patients presented with features of proximal tubular dysfunction leading to an erroneous diagnosis of renal Fanconi syndrome. The proximal tubulopathy disappeared after resolution of acidosis, indicating the importance of following proximal tubular function to establish the correct diagnosis. Growth retardation with a height below -2 standard deviation score was found in ten patients at presentation, but persisted in only three of these children once established on alkali treatment. Sensorineural hearing loss was found in five of the six patients with an ATP6V1B1 mutation. Only one patient with an ATP6V0A4 mutation had sensorineural hearing loss during childhood. Nine children developed medullary cysts, but without apparent clinical consequences. Cyst development in this cohort was not correlated with age at therapy onset, molecular diagnosis, growth parameters or renal function. In general, the prognosis of dRTA is good in children treated with alkali.

  12. Comparative Aspects of Canine Melanoma

    PubMed Central

    Nishiya, Adriana Tomoko; Massoco, Cristina Oliveira; Felizzola, Claudia Ronca; Perlmann, Eduardo; Batschinski, Karen; Tedardi, Marcello Vannucci; Garcia, Jéssica Soares; Mendonça, Priscila Pedra; Teixeira, Tarso Felipe; Zaidan Dagli, Maria Lucia

    2016-01-01

    Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas. PMID:29056717

  13. Molecular beam epitaxy growth of SrO buffer layers on graphite and graphene for the integration of complex oxides

    DOE PAGES

    Ahmed, Adam S.; Wen, Hua; Ohta, Taisuke; ...

    2016-04-27

    Here, we report the successful growth of high-quality SrO films on highly-ordered pyrolytic graphite (HOPG) and single-layer graphene by molecular beam epitaxy. The SrO layers have (001) orientation as confirmed by X-ray diffraction (XRD) while atomic force microscopy measurements show continuous pinhole-free films having rms surface roughness of <1.5 Å. Moreover, transport measurements of exfoliated graphene, after SrO deposition, show a strong dependence between the Dirac point and Sr oxidation. As a result, the SrO is leveraged as a buffer layer for more complex oxide integration via the demonstration of (001) oriented SrTiO3 grown atop a SrO/HOPG stack.

  14. Molecular beam epitaxy growth of SrO buffer layers on graphite and graphene for the integration of complex oxides

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

    Ahmed, Adam S.; Wen, Hua; Ohta, Taisuke

    Here, we report the successful growth of high-quality SrO films on highly-ordered pyrolytic graphite (HOPG) and single-layer graphene by molecular beam epitaxy. The SrO layers have (001) orientation as confirmed by X-ray diffraction (XRD) while atomic force microscopy measurements show continuous pinhole-free films having rms surface roughness of <1.5 Å. Moreover, transport measurements of exfoliated graphene, after SrO deposition, show a strong dependence between the Dirac point and Sr oxidation. As a result, the SrO is leveraged as a buffer layer for more complex oxide integration via the demonstration of (001) oriented SrTiO3 grown atop a SrO/HOPG stack.

  15. Mechanical and thermal stability of molecularly engineered copper-silica interfaces using organosilane nanolayers

    NASA Astrophysics Data System (ADS)

    Gandhi, Darshan Dinesh

    Future generation silicon integrated circuits requires new materials with low dielectric permittivity kappa < 2.0 and ultra-thin barrier layers (e.g., <3 nm) to create high-reliability, high-performance wiring. Preserving the structural and functional integrity of interfaces is a crucial aspect of realizing reliable integrated circuits with nanodevice components. Molecular nanolayers (MNLs) provide the unique ability to tailor interface properties by adjusting molecular termini, layering, branching or length, thereby making them attractive alternatives to conventional barrier materials. Developing a fundamental understanding of the stability and properties of MNLs at thin film interfaces, and their correlation with parameters such as terminal group chemistries molecular length and surface coverage are key to utilizing them in nanodevice applications. This work addresses some of the key challenges pertaining to modifying Cu-silica interfaces with MNLs with appropriate terminal groups. The resultant effects on, and the inter-relationships between, the chemical, mechanical and electrical properties are investigated. Modifying Cu-silica interface with MNLs results in increased Cu diffusioninduced time-to-failure when subject to electrothermal stresses. The extent of enhancement depends on the terminal chemistry of the MNLs interacting with the overlying Cu. Upon annealing, it is found that MNLs form strong covalent linkages at both Cu-MNL and MNL-silica interfaces resulting in unprecedented values of interface toughness, values exceeding 20 Jm-2. Although strong bonding at Cu-MNL and MNL-dielectric interfaces may be sufficient for blocking copper transport across polyelectrolyte MNL bilayers, strong interlayer molecular bonding is a necessary condition for interface toughening. Exposing MNLs to UV light, results in photo-oxidation of the terminal mercaptan groups. These photo-oxidized termini form strong complexes with Cu that results in enhancement by a factor-of-10

  16. Integrated Multiscale Modeling of Molecular Computing Devices. Final Report

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

    Tim Schulze

    2012-11-01

    The general theme of this research has been to expand the capabilities of a simulation technique, Kinetic Monte Carlo (KMC) and apply it to study self-assembled nano-structures on epitaxial thin films. KMC simulates thin film growth and evolution by replacing the detailed dynamics of the system's evolution, which might otherwise be studied using molecular dynamics, with an appropriate stochastic process.

  17. Selective Modulators of PPAR-γ Activity: Molecular Aspects Related to Obesity and Side-Effects

    PubMed Central

    Zhang, Fang; Lavan, Brian E.; Gregoire, Francine M.

    2007-01-01

    Peroxisome proliferator-activated receptor γ (PPAR-γ) is a key regulator of lipid metabolism and energy balance implicated in the development of insulin resistance and obesity. The identification of putative natural and synthetic ligands and activators of PPAR-γ has helped to unravel the molecular basis of its function, including molecular details regarding ligand binding, conformational changes of the receptor, and cofactor binding, leading to the emergence of the concept of selective PPAR-γ modulators (SPPARγMs). SPPARγMs bind in distinct manners to the ligand-binding pocket of PPAR-γ, leading to alternative receptor conformations, differential cofactor recruitment/displacement, differential gene expression, and ultimately differential biological responses. Based on this concept, new and improved antidiabetic agents for the treatment of diabetes are in development. This review summarizes the current knowledge on the mechanism of action and biological effects of recently characterized SPPARγMs, including metaglidasen/halofenate, PA-082, and the angiotensin receptor antagonists, recently characterized as a new class of SPPARγMs. PMID:17389769

  18. Methodological aspects of the molecular and histological study of prostate cancer: focus on PTEN.

    PubMed

    Ugalde-Olano, Aitziber; Egia, Ainara; Fernández-Ruiz, Sonia; Loizaga-Iriarte, Ana; Zuñiga-García, Patricia; Garcia, Stephane; Royo, Félix; Lacasa-Viscasillas, Isabel; Castro, Erika; Cortazar, Ana R; Zabala-Letona, Amaia; Martín-Martín, Natalia; Arruabarrena-Aristorena, Amaia; Torrano-Moya, Verónica; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Caro-Maldonado, Alfredo; González-Tampan, Jorge; Cachi-Fuentes, Guido; Bilbao, Elena; Montero, Rocío; Fernández, Sara; Arrieta, Edurne; Zorroza, Kerman; Castillo-Martín, Mireia; Serra, Violeta; Salazar, Eider; Macías-Cámara, Nuria; Tabernero, Jose; Baselga, Jose; Cordón-Cardo, Carlos; Aransay, Ana M; Villar, Amaia Del; Iovanna, Juan L; Falcón-Pérez, Juan M; Unda, Miguel; Bilbao, Roberto; Carracedo, Arkaitz

    2015-05-01

    Prostate cancer is among the most frequent cancers in men, and despite its high rate of cure, the high number of cases results in an elevated mortality worldwide. Importantly, prostate cancer incidence is dramatically increasing in western societies in the past decades, suggesting that this type of tumor is exquisitely sensitive to lifestyle changes. Prostate cancer frequently exhibits alterations in the PTEN gene (inactivating mutations or gene deletions) or at the protein level (reduced protein expression or altered sub-cellular compartmentalization). The relevance of PTEN in this type of cancer is further supported by the fact that the sole deletion of PTEN in the murine prostate epithelium recapitulates many of the features of the human disease. In order to study the molecular alterations in prostate cancer, we need to overcome the methodological challenges that this tissue imposes. In this review we present protocols and methods, using PTEN as proof of concept, to study different molecular characteristics of prostate cancer. Copyright © 2015. Published by Elsevier Inc.

  19. Engineering the System and Technical Integration

    NASA Technical Reports Server (NTRS)

    Blair, J. C.; Ryan, R. S.; Schutzenhofer, L. A.

    2011-01-01

    Approximately 80% of the problems encountered in aerospace systems have been due to a breakdown in technical integration and/or systems engineering. One of the major challenges we face in designing, building, and operating space systems is: how is adequate integration achieved for the systems various functions, parts, and infrastructure? This Contractor Report (CR) deals with part of the problem of how we engineer the total system in order to achieve the best balanced design. We will discuss a key aspect of this question - the principle of Technical Integration and its components, along with management and decision making. The CR will first provide an introduction with a discussion of the Challenges in Space System Design and meeting the challenges. Next is an overview of Engineering the System including Technical Integration. Engineering the System is expanded to include key aspects of the Design Process, Lifecycle Considerations, etc. The basic information and figures used in this CR were presented in a NASA training program for Program and Project Managers Development (PPMD) in classes at Georgia Tech and at Marshall Space Flight Center (MSFC). Many of the principles and illustrations are extracted from the courses we teach for MSFC.

  20. High-resolution monitoring of marine protists based on an observation strategy integrating automated on-board filtration and molecular analyses

    NASA Astrophysics Data System (ADS)

    Metfies, Katja; Schroeder, Friedhelm; Hessel, Johanna; Wollschläger, Jochen; Micheller, Sebastian; Wolf, Christian; Kilias, Estelle; Sprong, Pim; Neuhaus, Stefan; Frickenhaus, Stephan; Petersen, Wilhelm

    2016-11-01

    Information on recent biomass distribution and biogeography of photosynthetic marine protists with adequate temporal and spatial resolution is urgently needed to better understand the consequences of environmental change for marine ecosystems. Here we introduce and review a molecular-based observation strategy for high-resolution assessment of these protists in space and time. It is the result of extensive technology developments, adaptations and evaluations which are documented in a number of different publications, and the results of the recently completed field testing which are introduced in this paper. The observation strategy is organized at four different levels. At level 1, samples are collected at high spatiotemporal resolution using the remotely controlled automated filtration system AUTOFIM. Resulting samples can either be preserved for later laboratory analyses, or directly subjected to molecular surveillance of key species aboard the ship via an automated biosensor system or quantitative polymerase chain reaction (level 2). Preserved samples are analyzed at the next observational levels in the laboratory (levels 3 and 4). At level 3 this involves molecular fingerprinting methods for a quick and reliable overview of differences in protist community composition. Finally, selected samples can be used to generate a detailed analysis of taxonomic protist composition via the latest next generation sequencing technology (NGS) at level 4. An overall integrated dataset of the results based on the different analyses provides comprehensive information on the diversity and biogeography of protists, including all related size classes. At the same time the cost of the observation is optimized with respect to analysis effort and time.

  1. Multiple Roles of Integrin-Linked Kinase in Epidermal Development, Maturation and Pigmentation Revealed by Molecular Profiling

    PubMed Central

    Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E.; Dagnino, Lina

    2012-01-01

    Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function. PMID:22574216

  2. Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

    PubMed

    Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

    2012-01-01

    Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

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

    PubMed

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

    2014-05-06

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

  4. Marketing and Languages: An Integrative Model.

    ERIC Educational Resources Information Center

    McCall, Ian

    1988-01-01

    A framework is proposed for an integrated course in which knowledge of a language is consciously related to the processes of interpersonal communication and the cultural aspects of marketing and negotiation. (Editor)

  5. Molecular Diagnostic Analysis of Outbreak Scenarios

    ERIC Educational Resources Information Center

    Morsink, M. C.; Dekter, H. E.; Dirks-Mulder, A.; van Leeuwen, W. B.

    2012-01-01

    In the current laboratory assignment, technical aspects of the polymerase chain reaction (PCR) are integrated in the context of six different bacterial outbreak scenarios. The "Enterobacterial Repetitive Intergenic Consensus Sequence" (ERIC) PCR was used to analyze different outbreak scenarios. First, groups of 2-4 students determined optimal…

  6. G-DOC Plus - an integrative bioinformatics platform for precision medicine.

    PubMed

    Bhuvaneshwar, Krithika; Belouali, Anas; Singh, Varun; Johnson, Robert M; Song, Lei; Alaoui, Adil; Harris, Michael A; Clarke, Robert; Weiner, Louis M; Gusev, Yuriy; Madhavan, Subha

    2016-04-30

    G-DOC Plus is a data integration and bioinformatics platform that uses cloud computing and other advanced computational tools to handle a variety of biomedical BIG DATA including gene expression arrays, NGS and medical images so that they can be analyzed in the full context of other omics and clinical information. G-DOC Plus currently holds data from over 10,000 patients selected from private and public resources including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the recently added datasets from REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT), caArray studies of lung and colon cancer, ImmPort and the 1000 genomes data sets. The system allows researchers to explore clinical-omic data one sample at a time, as a cohort of samples; or at the level of population, providing the user with a comprehensive view of the data. G-DOC Plus tools have been leveraged in cancer and non-cancer studies for hypothesis generation and validation; biomarker discovery and multi-omics analysis, to explore somatic mutations and cancer MRI images; as well as for training and graduate education in bioinformatics, data and computational sciences. Several of these use cases are described in this paper to demonstrate its multifaceted usability. G-DOC Plus can be used to support a variety of user groups in multiple domains to enable hypothesis generation for precision medicine research. The long-term vision of G-DOC Plus is to extend this translational bioinformatics platform to stay current with emerging omics technologies and analysis methods to continue supporting novel hypothesis generation, analysis and validation for integrative biomedical research. By integrating several aspects of the disease and exposing various data elements, such as outpatient lab workup, pathology, radiology, current treatments, molecular signatures and expected outcomes over a web interface, G-DOC Plus will continue to strengthen precision medicine research. G-DOC Plus is available

  7. Ten years of R&D and full automation in molecular diagnosis.

    PubMed

    Greub, Gilbert; Sahli, Roland; Brouillet, René; Jaton, Katia

    2016-01-01

    A 10-year experience of our automated molecular diagnostic platform that carries out 91 different real-time PCR is described. Progresses and future perspectives in molecular diagnostic microbiology are reviewed: why automation is important; how our platform was implemented; how homemade PCRs were developed; the advantages/disadvantages of homemade PCRs, including the critical aspects of troubleshooting and the need to further reduce the turnaround time for specific samples, at least for defined clinical settings such as emergencies. The future of molecular diagnosis depends on automation, and in a novel perspective, it is time now to fully acknowledge the true contribution of molecular diagnostic and to reconsider the indication for PCR, by also using these tests as first-line assays.

  8. Regeneration in the Pituitary After Cell-Ablation Injury: Time-Related Aspects and Molecular Analysis.

    PubMed

    Willems, Christophe; Fu, Qiuli; Roose, Heleen; Mertens, Freya; Cox, Benoit; Chen, Jianghai; Vankelecom, Hugo

    2016-02-01

    We recently showed that the mouse pituitary holds regenerative competence. Young-adult GHCre/iDTR mice, expressing diphtheria toxin (DT) receptor in GH-producing cells, regenerate the GH(+) cells, as ablated by 3-day DT treatment (3DT), up to 60% after 5 months. The pituitary's stem cells participate in this restoration process. Here, we characterized this regenerative capacity in relation to age and recovery period and started to search for underlying molecular mechanisms. Extending the recovery period (up to 19 mo) does not result in higher regeneration levels. In addition, the regenerative competence disappears at older age, coinciding with a reduction in pituitary stem cell number and fitness. Surprisingly, prolonging DT treatment of young-adult mice to 10 days (10DT) completely blocks the regeneration, although the stem cell compartment still reacts by promptly expanding, and retains in vitro stem cell functionality. To obtain a first broad view on molecular grounds underlying reparative capacity and/or failure, the stem cell-clustering side population was analyzed by whole-genome expression analysis. A number of stemness factors and components of embryonic, epithelial-mesenchymal transition, growth factor and Hippo pathways are higher expressed in the stem cell-clustering side population of the regenerating pituitary (after 3DT) when compared with the basal gland and to the nonregenerating pituitary (after 10DT). Together, the regenerative capacity of the pituitary is limited both in age-related terms and final efficacy, and appears to rely on stem cell-associated pathway activation. Dissection of the molecular profiles may eventually identify targets to induce or boost regeneration in situations of (injury-related) pituitary deficiency.

  9. Fine- and hyperfine-structure effects in molecular photoionization. II. Resonance-enhanced multiphoton ionization and hyperfine-selective generation of molecular cations

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

    Germann, Matthias; Willitsch, Stefan, E-mail: stefan.willitsch@unibas.ch

    2016-07-28

    Resonance-enhanced multiphoton ionization (REMPI) is a widely used technique for studying molecular photoionization and producing molecular cations for spectroscopy and dynamics studies. Here, we present a model for describing hyperfine-structure effects in the REMPI process and for predicting hyperfine populations in molecular ions produced by this method. This model is a generalization of our model for fine- and hyperfine-structure effects in one-photon ionization of molecules presented in Paper I [M. Germann and S. Willitsch, J. Chem. Phys. 145, 044314 (2016)]. This generalization is achieved by covering two main aspects: (1) treatment of the neutral bound-bound transition including the hyperfine structuremore » that makes up the first step of the REMPI process and (2) modification of our ionization model to account for anisotropic populations resulting from this first excitation step. Our findings may be used for analyzing results from experiments with molecular ions produced by REMPI and may serve as a theoretical background for hyperfine-selective ionization experiments.« less

  10. Frogs as integrative models for understanding digestive organ development and evolution.

    PubMed

    Womble, Mandy; Pickett, Melissa; Nascone-Yoder, Nanette

    2016-03-01

    The digestive system comprises numerous cells, tissues and organs that are essential for the proper assimilation of nutrients and energy. Many aspects of digestive organ function are highly conserved among vertebrates, yet the final anatomical configuration of the gut varies widely between species, especially those with different diets. Improved understanding of the complex molecular and cellular events that orchestrate digestive organ development is pertinent to many areas of biology and medicine, including the regeneration or replacement of diseased organs, the etiology of digestive organ birth defects, and the evolution of specialized features of digestive anatomy. In this review, we highlight specific examples of how investigations using Xenopus laevis frog embryos have revealed insight into the molecular and cellular dynamics of digestive organ patterning and morphogenesis that would have been difficult to obtain in other animal models. Additionally, we discuss recent studies of gut development in non-model frog species with unique feeding strategies, such as Lepidobatrachus laevis and Eleutherodactylous coqui, which are beginning to provide glimpses of the evolutionary mechanisms that may generate morphological variation in the digestive tract. The unparalleled experimental versatility of frog embryos make them excellent, integrative models for studying digestive organ development across multiple disciplines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Frogs as integrative models for understanding digestive organ development and evolution

    PubMed Central

    Womble, Mandy; Pickett, Melissa; Nascone-Yoder, Nanette

    2016-01-01

    The digestive system comprises numerous cells, tissues and organs that are essential for the proper assimilation of nutrients and energy. Many aspects of digestive organ function are highly conserved among vertebrates, yet the final anatomical configuration of the gut varies widely between species, especially those with different diets. Improved understanding of the complex molecular and cellular events that orchestrate digestive organ development is pertinent to many areas of biology and medicine, including the regeneration or replacement of diseased organs, the etiology of digestive organ birth defects, and the evolution of specialized features of digestive anatomy. In this review, we highlight specific examples of how investigations using Xenopus laevis frog embryos have revealed insight into the molecular and cellular dynamics of digestive organ patterning and morphogenesis that would have been difficult to obtain in other animal models. Additionally, we discuss recent studies of gut development in non-model frog species with unique feeding strategies, such as Lepidobatrachus laev is and Eleutherodactylouscoqui, which are beginning to provide glimpses of the evolutionary mechanisms that may generate morphological variation in the digestive tract. The unparalleled experimental versatility of frog embryos make them excellent, integrative models for studying digestive organ development across multiple disciplines. PMID:26851628

  12. An Integration of Math with Auto Technician Courses

    ERIC Educational Resources Information Center

    Valenzuela, Hector

    2012-01-01

    This article describes the development of the contextualized math, the course design, student teaching and daily interaction with the students, and the implementation aspects of the research project designed to develop contextualized mathematics and integrate it into the Auto Technician courses. The applied math curriculum was integrated into…

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

    PubMed

    Khavinson, V Kh; Lin'kova, N S

    2012-01-01

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

  14. Centro de Biologia Molecular "Severo Ochoa": a center for basic research into Alzheimer's disease.

    PubMed

    Avila, Jesus; Hernandez, Felix; Wandosell, Francisco; Lucas, Jose J; Esteban, Jose A; Ledesma, M Dolores; Bullido, Maria J

    2010-01-01

    One important aspect of studies carried out at the Center for Molecular Biology "Severo Ochoa" is focused on basic aspects of Alzheimer's disease, mainly the search for suitable therapeutic targets for this disorder. Several groups at the Center are involved in these studies, and, in this spotlight, the work they are carrying out will be described.

  15. New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

    PubMed Central

    Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

    2011-01-01

    Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC. PMID:22028706

  16. New aspects in the differential diagnosis and therapy of bladder pain syndrome/interstitial cystitis.

    PubMed

    Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

    2011-01-01

    Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical "columns": (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

  17. Molecular and nanoscale materials and devices in electronics.

    PubMed

    Fu, Lei; Cao, Lingchao; Liu, Yunqi; Zhu, Daoben

    2004-12-13

    Over the past several years, there have been many significant advances toward the realization of electronic computers integrated on the molecular scale and a much greater understanding of the types of materials that will be useful in molecular devices and their properties. It was demonstrated that individual molecules could serve as incomprehensibly tiny switch and wire one million times smaller than those on conventional silicon microchip. This has resulted very recently in the assembly and demonstration of tiny computer logic circuits built from such molecular scale devices. The purpose of this review is to provide a general introduction to molecular and nanoscale materials and devices in electronics.

  18. An aspect-oriented approach for designing safety-critical systems

    NASA Astrophysics Data System (ADS)

    Petrov, Z.; Zaykov, P. G.; Cardoso, J. P.; Coutinho, J. G. F.; Diniz, P. C.; Luk, W.

    The development of avionics systems is typically a tedious and cumbersome process. In addition to the required functions, developers must consider various and often conflicting non-functional requirements such as safety, performance, and energy efficiency. Certainly, an integrated approach with a seamless design flow that is capable of requirements modelling and supporting refinement down to an actual implementation in a traceable way, may lead to a significant acceleration of development cycles. This paper presents an aspect-oriented approach supported by a tool chain that deals with functional and non-functional requirements in an integrated manner. It also discusses how the approach can be applied to development of safety-critical systems and provides experimental results.

  19. Molecular ecology of aquatic communities: Reflections and future directions

    USGS Publications Warehouse

    Zehr, J.P.; Voytek, M.A.

    1999-01-01

    During the 1980s, many new molecular biology techniques were developed, providing new capabilities for studying the genetics and activities of organisms. Biologists and ecologists saw the promise that these techniques held for studying different aspects of organisms, both in culture and in the natural environment. In less than a decade, these techniques were adopted by a large number of researchers studying many types of organisms in diverse environments. Much of the molecular-level information acquired has been used to address questions of evolution, biogeography, population structure and biodiversity. At this juncture, molecular ecologists are poised to contribute to the study of the fundamental characteristics underlying aquatic community structure. The goal of this overview is to assess where we have been, where we are now and what the future holds for revealing the basis of community structure and function with molecular-level information.

  20. Quality of care and service trajectories for people with intellectual disabilities: defining the aspects of quality from the client's perspective.

    PubMed

    Barelds, Anna; van de Goor, Ien; van Heck, Guus; Schols, Jos

    2010-03-01

    Care and service trajectories for people with intellectual disabilities (i.e. people with mental retardations) are routes within the healthcare delivery system that consist of all the steps that people with intellectual disabilities and their families have to take in order to realise the needed care and services. This article aims to identify the quality aspects of trajectories that are considered important by people with intellectual disabilities and their parents/relatives. In addition, it examines how these aspects are related to quality determinants mentioned in the literature on integrated care and to authoritative models for quality assessment of care and service delivery. Quality aspects were collected during eight focus group discussions with people with intellectual disabilities or their parents/relatives. In addition, quality determinants of integrated care and authoritative models for quality assessment were selected by means of a thorough review of the literature. Finally, the quality aspects identified using focus groups were compared to the determinants and models found in the literature. The quality aspects presented by people with intellectual disabilities referred particularly to the immediate situation in receiving care and services, such as 'keeping appointments' and 'time and attention', whereas parents/relatives also referred to broader 'organisational issues', such as 'access to support' and 'problems with placement'. The quality aspects, however, are minimally related to the quality determinants of integrated care, probably because clients and their parents/relatives find it difficult to have an overview of the coherence between the various actions that have to be performed, when going through the trajectories. In contrast, the quality aspects seem to fit into the domains of the authoritative models for quality assessment, probably because of the minimal focus of the models on long-term aspects in care and service delivery.

  1. A New Integrated Approach to Taxonomy: The Fusion of Molecular and Morphological Systematics with Type Material in Benthic Foraminifera

    PubMed Central

    Roberts, Angela; Austin, William; Evans, Katharine; Bird, Clare; Schweizer, Magali; Darling, Kate

    2016-01-01

    A robust and consistent taxonomy underpins the use of fossil material in palaeoenvironmental research and long-term assessment of biodiversity. This study presents a new integrated taxonomic protocol for benthic foraminifera by unequivocally reconciling the traditional taxonomic name to a specific genetic type. To implement this protocol, a fragment of the small subunit ribosomal RNA (SSU rRNA) gene is used in combination with 16 quantitative morphometric variables to fully characterise the benthic foraminiferal species concept of Elphidium williamsoni Haynes, 1973. A combination of live contemporary topotypic specimens, original type specimens and specimens of genetic outliers were utilised in this study. Through a series of multivariate statistical tests we illustrate that genetically characterised topotype specimens are morphologically congruent with both the holotype and paratype specimens of E. williamsoni Haynes, 1973. We present the first clear link between morphologically characterised type material and the unique SSU rRNA genetic type of E. williamsoni. This example provides a standard framework for the benthic foraminifera which bridges the current discontinuity between molecular and morphological lines of evidence, allowing integration with the traditional Linnaean roots of nomenclature to offer a new prospect for taxonomic stability. PMID:27388271

  2. Molecular-Scale Electronics: From Concept to Function.

    PubMed

    Xiang, Dong; Wang, Xiaolong; Jia, Chuancheng; Lee, Takhee; Guo, Xuefeng

    2016-04-13

    Creating functional electrical circuits using individual or ensemble molecules, often termed as "molecular-scale electronics", not only meets the increasing technical demands of the miniaturization of traditional Si-based electronic devices, but also provides an ideal window of exploring the intrinsic properties of materials at the molecular level. This Review covers the major advances with the most general applicability and emphasizes new insights into the development of efficient platform methodologies for building reliable molecular electronic devices with desired functionalities through the combination of programmed bottom-up self-assembly and sophisticated top-down device fabrication. First, we summarize a number of different approaches of forming molecular-scale junctions and discuss various experimental techniques for examining these nanoscale circuits in details. We then give a full introduction of characterization techniques and theoretical simulations for molecular electronics. Third, we highlight the major contributions and new concepts of integrating molecular functionalities into electrical circuits. Finally, we provide a critical discussion of limitations and main challenges that still exist for the development of molecular electronics. These analyses should be valuable for deeply understanding charge transport through molecular junctions, the device fabrication process, and the roadmap for future practical molecular electronics.

  3. Molecular clock on a neutral network.

    PubMed

    Raval, Alpan

    2007-09-28

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

  4. Molecular Clock on a Neutral Network

    NASA Astrophysics Data System (ADS)

    Raval, Alpan

    2007-09-01

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

  5. Molecular basis of angiosperm tree architecture.

    PubMed

    Hollender, Courtney A; Dardick, Chris

    2015-04-01

    The architecture of trees greatly impacts the productivity of orchards and forestry plantations. Amassing greater knowledge on the molecular genetics that underlie tree form can benefit these industries, as well as contribute to basic knowledge of plant developmental biology. This review describes the fundamental components of branch architecture, a prominent aspect of tree structure, as well as genetic and hormonal influences inferred from studies in model plant systems and from trees with non-standard architectures. The bulk of the molecular and genetic data described here is from studies of fruit trees and poplar, as these species have been the primary subjects of investigation in this field of science. No claim to original US Government works. New Phytologist © 2014 New Phytologist Trust.

  6. Exploring the molecular aspects associated with testicular germ cell tumors: a review

    PubMed Central

    Facchini, Gaetano; Rossetti, Sabrina; Cavaliere, Carla; D’Aniello, Carmine; Di Franco, Rossella; Iovane, Gelsomina; Grimaldi, Giovanni; Piscitelli, Raffaele; Muto, Paolo; Botti, Gerardo; Perdonà, Sisto; Veneziani, Bianca Maria; Berretta, Massimiliano; Montanari, Micaela

    2018-01-01

    Testicular germ cell tumors (TGCTs) represent the most common solid tumors affecting young men. They constitute a distinct entity because of their embryonic origin and their unique biological behavior. Recent preclinical data regarding biological signaling machinery as well as genetic and epigenetic mechanisms associated with molecular patterns of tumors have contribute to explain the pathogenesis and the differentiation of TGCTs and to understand the mechanisms responsible for the development of resistance to treatment. In this review, we discuss the main genetic and epigenetic events associated with TGCTs development in order to better define their role in the pathogenesis of these tumors and in cisplatin-acquired resistance. PMID:29416701

  7. A path integral molecular dynamics study of the hyperfine coupling constants of the muoniated and hydrogenated acetone radicals

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

    Oba, Yuki; Kawatsu, Tsutomu; Tachikawa, Masanori, E-mail: tachi@yokohama-cu.ac.jp

    2016-08-14

    The on-the-fly ab initio density functional path integral molecular dynamics (PIMD) simulations, which can account for both the nuclear quantum effect and thermal effect, were carried out to evaluate the structures and “reduced” isotropic hyperfine coupling constants (HFCCs) for muoniated and hydrogenated acetone radicals (2-muoxy-2-propyl and 2-hydoxy-2-propyl) in vacuo. The reduced HFCC value from a simple geometry optimization calculation without both the nuclear quantum effect and thermal effect is −8.18 MHz, and that by standard ab initio molecular dynamics simulation with only the thermal effect and without the nuclear quantum effect is 0.33 MHz at 300 K, where these twomore » methods cannot distinguish the difference between muoniated and hydrogenated acetone radicals. In contrast, the reduced HFCC value of the muoniated acetone radical by our PIMD simulation is 32.1 MHz, which is about 8 times larger than that for the hydrogenated radical of 3.97 MHz with the same level of calculation. We have found that the HFCC values are highly correlated with the local molecular structures; especially, the Mu—O bond length in the muoniated acetone radical is elongated due to the large nuclear quantum effect of the muon, which makes the expectation value of the HFCC larger. Although our PIMD result calculated in vacuo is about 4 times larger than the measured experimental value in aqueous solvent, the ratio of these HFCC values between muoniated and hydrogenated acetone radicals in vacuo is in reasonable agreement with the ratio of the experimental values in aqueous solvent (8.56 MHz and 0.9 MHz); the explicit presence of solvent molecules has a major effect on decreasing the reduced muon HFCC of in vacuo calculations for the quantitative reproduction.« less

  8. Molecular hydrogen in sports medicine: new therapeutic perspectives.

    PubMed

    Ostojic, S M

    2015-04-01

    In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. Beneficial effects of molecular hydrogen in clinical environment are observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. A number of more recent studies have reported that molecular hydrogen affects cell signal transduction and acts as an alkalizing agent, with these newly identified mechanisms of action having the potential to widen its application in clinical medicine even further. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Integration of Basic Sciences in Health's Courses

    ERIC Educational Resources Information Center

    Azzalis, L. A.; Giavarotti, L.; Sato, S. N.; Barros, N. M. T.; Junqueira, V. B. C.; Fonseca, F. L. A.

    2012-01-01

    Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular Biology are essential to the understanding and treatment of an elevated number of illnesses, but often they are studied separately, with no integration between them. This article proposes a model for basic sciences integration based on problem-based learning (PBL) and…

  10. Rapid HIS, RIS, PACS Integration Using Graphical CASE Tools

    NASA Astrophysics Data System (ADS)

    Taira, Ricky K.; Breant, Claudine M.; Stepczyk, Frank M.; Kho, Hwa T.; Valentino, Daniel J.; Tashima, Gregory H.; Materna, Anthony T.

    1994-05-01

    We describe the clinical requirements of the integrated federation of databases and present our client-mediator-server design. The main body of the paper describes five important aspects of integrating information systems: (1) global schema design, (2) establishing sessions with remote database servers, (3) development of schema translators, (4) integration of global system triggers, and (5) development of job workflow scripts.

  11. On-demand drawing of high aspect-ratio, microsphere-tipped elastomeric micropillars

    NASA Astrophysics Data System (ADS)

    Li, Qiang; Kim, Jaeyoun

    2017-08-01

    High aspect-ratio elastomeric micropillars are widely used in a plethora of applications, such as functional surfaces, actuators, and sensors. Their fabrication at arbitrary positions on non-planar substrates, however, has rarely been reported. Here we demonstrate a new technique for facile fabrication of high aspect-ratio, microsphere-tipped elastomeric micropillars on structures with uncommon geometries. As a proof-of-concept exemplary application, a fiber optic contact sensor is realized by integrating a micropillar onto the end facet of an optical fiber. Overall, both the fabrication technique and the resulting outcomes of this work will add new tools to the toolbox of soft-MEMS and softrobotics.

  12. Macroergonomic aspects in the design of development programs in IDCs.

    PubMed

    Coelho, Denis A; Ferrara, Patricia R; Couvinhas, Ana F; Lima, Tânia M; Walter, Jake K

    2012-01-01

    This paper revisits three reports on ergonomic aspects of development initiatives taking place in Industrially Developing Countries (IDCs). These include a macro-ergonomics intervention in a habitation community in Cape Verde (aimed at designing solutions contributing to sustainable development), the evolution of poultry growers' control strategies as an integrative broiler operation is introduced in Mozambique, and a set of macro-ergonomic considerations related to the Agro Forestry Village Project in Mozambique. The paper seeks to set the reviewed development endeavors against the backdrop of the goals of ergonomics interventions. This reflection may inform development agents in future processes of design and implementation of integrated community and work systems transformation.

  13. The integrative future of taxonomy

    PubMed Central

    2010-01-01

    Background Taxonomy is the biological discipline that identifies, describes, classifies and names extant and extinct species and other taxa. Nowadays, species taxonomy is confronted with the challenge to fully incorporate new theory, methods and data from disciplines that study the origin, limits and evolution of species. Results Integrative taxonomy has been proposed as a framework to bring together these conceptual and methodological developments. Here we review perspectives for an integrative taxonomy that directly bear on what species are, how they can be discovered, and how much diversity is on Earth. Conclusions We conclude that taxonomy needs to be pluralistic to improve species discovery and description, and to develop novel protocols to produce the much-needed inventory of life in a reasonable time. To cope with the large number of candidate species revealed by molecular studies of eukaryotes, we propose a classification scheme for those units that will facilitate the subsequent assembly of data sets for the formal description of new species under the Linnaean system, and will ultimately integrate the activities of taxonomists and molecular biologists. PMID:20500846

  14. Aspect Ratio Model for Radiation-Tolerant Dummy Gate-Assisted n-MOSFET Layout.

    PubMed

    Lee, Min Su; Lee, Hee Chul

    2014-01-01

    In order to acquire radiation-tolerant characteristics in integrated circuits, a dummy gate-assisted n-type metal oxide semiconductor field effect transistor (DGA n-MOSFET) layout was adopted. The DGA n-MOSFET has a different channel shape compared with the standard n-MOSFET. The standard n-MOSFET has a rectangular channel shape, whereas the DGA n-MOSFET has an extended rectangular shape at the edge of the source and drain, which affects its aspect ratio. In order to increase its practical use, a new aspect ratio model is proposed for the DGA n-MOSFET and this model is evaluated through three-dimensional simulations and measurements of the fabricated devices. The proposed aspect ratio model for the DGA n-MOSFET exhibits good agreement with the simulation and measurement results.

  15. Aspect Ratio Model for Radiation-Tolerant Dummy Gate-Assisted n-MOSFET Layout

    PubMed Central

    Lee, Min Su; Lee, Hee Chul

    2014-01-01

    In order to acquire radiation-tolerant characteristics in integrated circuits, a dummy gate-assisted n-type metal oxide semiconductor field effect transistor (DGA n-MOSFET) layout was adopted. The DGA n-MOSFET has a different channel shape compared with the standard n-MOSFET. The standard n-MOSFET has a rectangular channel shape, whereas the DGA n-MOSFET has an extended rectangular shape at the edge of the source and drain, which affects its aspect ratio. In order to increase its practical use, a new aspect ratio model is proposed for the DGA n-MOSFET and this model is evaluated through three-dimensional simulations and measurements of the fabricated devices. The proposed aspect ratio model for the DGA n-MOSFET exhibits good agreement with the simulation and measurement results. PMID:27350975

  16. Integrated Testing of a 4-Bed Molecular Sieve and a Temperature-Swing Adsorption Compressor for Closed-Loop Air Revitalization

    NASA Technical Reports Server (NTRS)

    Knox, James C.; Mulloth, Lila M.; Affleck, David L.

    2004-01-01

    Accumulation and subsequent compression of carbon dioxide that is removed from space cabin are two important processes involved in a closed-loop air revitalization scheme of the International Space Station (ISS). The 4-Bed Molecular Sieve (4BMS) of ISS currently operates in an open loop mode without a compressor. This paper reports the integrated 4BMS and liquid-cooled TSAC testing conducted during the period of March 3 to April 18, 2003. The TSAC prototype was developed at NASA Ames Research Center (ARC). The 4BMS was modified to a functionally flight-like condition at NASA Marshall Space Flight Center (MSFC). Testing was conducted at MSFC. The paper provides details of the TSAC operation at various CO2 loadings and corresponding performance of CDRA.

  17. Batten Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Future Directions

    PubMed Central

    Dolisca, Sarah-Bianca; Mehta, Mitali; Pearce, David A.; Mink, Jonathan W.; Maria, Bernard L.

    2014-01-01

    The neuronal ceroid lipofuscinoses, collectively the most common neurodegenerative disorders of childhood, are primarily caused by an autosomal recessive genetic mutation leading to a lysosomal storage disease. Clinically these diseases manifest at varying ages of onset, and associated symptoms include cognitive decline, movement disorders, seizures, and retinopathy. The underlying cell biology and biochemistry that cause the clinical phenotypes of neuronal ceroid lipofuscinoses are still being elaborated. The 2012 Neurobiology of Disease in Children Symposium, held in conjunction with the 41st Annual Meeting of the Child Neurology Society, aimed to (1) provide a survey of the currently accepted forms of neuronal ceroid lipofuscinoses and their associated genetic mutations and clinical phenotypes; (2) highlight the specific pathology of Batten disease; (3) discuss the contemporary understanding of the molecular mechanisms that lead to pathology; and (4) introduce strategies that are being translated from bench to bedside as potential therapeutics. PMID:23838031

  18. Molecular aspects of metal oxide nanoparticle (MO-NPs) mediated pharmacological effects.

    PubMed

    Tuli, Hardeep Singh; Kashyap, Dharambir; Bedi, Simranjeet Kaur; Kumar, Pardeep; Kumar, Gaurav; Sandhu, Sardul Singh

    2015-12-15

    Metal oxide nanoparticles (MO-NPs) are the multidisciplinary nano-scaled molecules which are being used in the diagnosis and treatment of the challenging diseases including cancer. Evidence suggest that antimicrobial formulations in the form of MO-NPs can be possibly used as effective antimicrobial agents. In addition, MO-NPs are known to target various cellular signaling pathways associated with apoptosis, angiogenesis, metastasis and inflammation of cancer. In combination with other chemotherapeutic/anticancer agents, MO-NPs not only increase their bioavailability and efficacy but also lower down the requirement of active dosages. To date, to our knowledge there is no single comprehensive report on cellular and molecular interactions of MO-NPs which have been well elaborated in this review. Also we highlight various action mechanisms through which MO-NPs act as antimicrobial, anticancer, antioxidant and anti-inflammatory agents. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2012-01-01

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

  20. Pernicious Anemia: Fundamental and Practical Aspects in Diagnosis.

    PubMed

    Tun, Aung Myint; Thein, Kyaw Zin; Myint, Zin War; Oo, Thein Hlaing

    2017-11-08

    Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity and diverse clinical presentations. Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for the evaluation of cobalamin deficiency and PA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Tetrametallic molecular catalysts for photochemical water oxidation.

    PubMed

    Sartorel, Andrea; Bonchio, Marcella; Campagna, Sebastiano; Scandola, Franco

    2013-03-21

    Among molecular water oxidation catalysts (WOCs), those featuring a reactive set of four multi-redox transition metals can leverage an extraordinary interplay of electronic and structural properties. These are of particular interest, owing to their close structural, and possibly functional, relationship to the oxygen evolving complex of natural photosynthesis. In this review, special attention is given to two classes of tetrametallic molecular WOCs: (i) M(4)O(4) cubane-type structures stabilized by simple organic ligands, and (ii) systems in which a tetranuclear metal core is stabilized by coordination of two polyoxometalate (POM) ligands. Recent work in this rapidly evolving field is reviewed, with particular emphasis on photocatalytic aspects. Special attention is given to studies addressing the mechanistic complexity of these systems, sometimes overlooked in the rush for oxygen evolving performance. The complementary role of molecular WOCs and their relationship with bulk oxides and heterogeneous catalysis are discussed.

  2. PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator.

    PubMed

    Mezan, Shaul; Feuz, Jean Daniel; Deplancke, Bart; Kadener, Sebastian

    2016-10-11

    Circadian clocks generate 24-hr rhythms in physiology and behavior. Despite numerous studies, it is still uncertain how circadian rhythms emerge from their molecular and neural constituents. Here, we demonstrate a tight connection between the molecular and neuronal circadian networks. Using fluorescent transcriptional reporters in a Drosophila ex vivo brain culture system, we identified a reciprocal negative regulation between the master circadian regulator CLK and expression of pdf, the main circadian neuropeptide. We show that PDF feedback is required for maintaining normal oscillation pattern in CLK-driven transcription. Interestingly, we found that CLK and neuronal firing suppresses pdf transcription, likely through a common pathway involving the transcription factors DHR38 and SR, establishing a direct link between electric activity and the circadian system. In sum, our work provides evidence for the existence of an uncharacterized CLK-PDF feedback loop that tightly wraps together the molecular oscillator with the circadian neuronal network in Drosophila. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Tagging and purifying proteins to teach molecular biology and advanced biochemistry.

    PubMed

    Roecklein-Canfield, Jennifer A; Lopilato, Jane

    2004-11-01

    Two distinct courses, "Molecular Biology" taught by the Biology Department and "Advanced Biochemistry" taught by the Chemistry Department, complement each other and, when taught in a coordinated and integrated way, can enhance student learning and understanding of complex material. "Molecular Biology" is a comprehensive lecture-based course with a 3-h laboratory once a week, while "Advanced Biochemistry" is a completely laboratory-based course with lecture fully integrated around independent student projects. Both courses emphasize and utilize cutting-edge technology. Teaching across departmental boundaries allows students access to faculty expertise and techniques rarely used at the undergraduate level, namely the tagging of proteins and their use in protein purification. Copyright © 2004 International Union of Biochemistry and Molecular Biology, Inc.

  4. RoBuST: an integrated genomics resource for the root and bulb crop families Apiaceae and Alliaceae

    PubMed Central

    2010-01-01

    Background Root and bulb vegetables (RBV) include carrots, celeriac (root celery), parsnips (Apiaceae), onions, garlic, and leek (Alliaceae)—food crops grown globally and consumed worldwide. Few data analysis platforms are currently available where data collection, annotation and integration initiatives are focused on RBV plant groups. Scientists working on RBV include breeders, geneticists, taxonomists, plant pathologists, and plant physiologists who use genomic data for a wide range of activities including the development of molecular genetic maps, delineation of taxonomic relationships, and investigation of molecular aspects of gene expression in biochemical pathways and disease responses. With genomic data coming from such diverse areas of plant science, availability of a community resource focused on these RBV data types would be of great interest to this scientific community. Description The RoBuST database has been developed to initiate a platform for collecting and organizing genomic information useful for RBV researchers. The current release of RoBuST contains genomics data for 294 Alliaceae and 816 Apiaceae plant species and has the following features: (1) comprehensive sequence annotations of 3663 genes 5959 RNAs, 22,723 ESTs and 11,438 regulatory sequence elements from Apiaceae and Alliaceae plant families; (2) graphical tools for visualization and analysis of sequence data; (3) access to traits, biosynthetic pathways, genetic linkage maps and molecular taxonomy data associated with Alliaceae and Apiaceae plants; and (4) comprehensive plant splice signal repository of 659,369 splice signals collected from 6015 plant species for comparative analysis of plant splicing patterns. Conclusions RoBuST, available at http://robust.genome.com, provides an integrated platform for researchers to effortlessly explore and analyze genomic data associated with root and bulb vegetables. PMID:20691054

  5. Molecular biology of potyviruses.

    PubMed

    Revers, Frédéric; García, Juan Antonio

    2015-01-01

    Potyvirus is the largest genus of plant viruses causing significant losses in a wide range of crops. Potyviruses are aphid transmitted in a nonpersistent manner and some of them are also seed transmitted. As important pathogens, potyviruses are much more studied than other plant viruses belonging to other genera and their study covers many aspects of plant virology, such as functional characterization of viral proteins, molecular interaction with hosts and vectors, structure, taxonomy, evolution, epidemiology, and diagnosis. Biotechnological applications of potyviruses are also being explored. During this last decade, substantial advances have been made in the understanding of the molecular biology of these viruses and the functions of their various proteins. After a general presentation on the family Potyviridae and the potyviral proteins, we present an update of the knowledge on potyvirus multiplication, movement, and transmission and on potyvirus/plant compatible interactions including pathogenicity and symptom determinants. We end the review providing information on biotechnological applications of potyviruses. © 2015 Elsevier Inc. All rights reserved.

  6. Fiber sensors for molecular detection

    NASA Astrophysics Data System (ADS)

    Gu, Claire; Yang, Xuan; Zhang, Jin; Newhouse, Rebecca; Cao, Liangcai

    2010-11-01

    The demand on sensors for detecting chemical and biological agents is greater than ever before, including medical, environmental, food safety, military, and security applications. At present, most detection or sensing techniques tend to be either non-molecular specific, bulky, expensive, relatively inaccurate, or unable to provide real time data. Clearly, alternative sensing technologies are urgently needed. Recently, we have been working to develop a compact fiber optic surface enhanced Raman scattering (SERS) sensor system that integrates various novel ideas to achieve compactness, high sensitivity and consistency, molecular specificity, and automatic preliminary identification capabilities. The unique sensor architecture is expected to bring SERS sensors to practical applications due to a combination of 1) novel SERS substrates that provide the high sensitivity and consistency, molecular specificity, and applicability to a wide range of compounds; 2) a unique hollow core optical fiber probe with double SERS substrate structure that provides the compactness, reliability, low cost, and ease of sampling; and 3) an innovative matched spectral filter set that provides automatic preliminary molecule identification. In this paper, we will review the principle of operation and some of the important milestones of fiber SERS sensor development with emphasis on our recent work to integrate photonic crystal fiber SERS probes with a portable Raman spectrometer and to demonstrate a matched spectral filter for molecule identification.

  7. The Future of Molecular Analysis in Melanoma: Diagnostics to Direct Molecularly Targeted Therapy.

    PubMed

    Akabane, Hugo; Sullivan, Ryan J

    2016-02-01

    Melanoma is a malignancy of pigment-producing cells that is driven by a variety of genetic mutations and aberrations. In most cases, this leads to upregulation of the mitogen-activated protein kinase (MAPK) pathway through activating mutations of upstream mediators of the pathway including BRAF and NRAS. With the advent of effective MAPK pathway inhibitors, including the US FDA-approved BRAF inhibitors vemurafenib and dabrafenib and MEK inhibitor trametinib, molecular analysis has become an integral part of the care of patients with metastatic melanoma. In this article, the key molecular targets and strategies to inhibit these targets therapeutically are presented, and the techniques of identifying these targets, in both tissue and blood, are discussed.

  8. Integrating multiple aspects of mitochondrial dynamics in neurons: Age-related differences and dynamic changes in a chronic rotenone model

    PubMed Central

    Arnold, Beth; Cassady, Steven J.; Van Laar, Victor S.; Berman, Sarah B.

    2010-01-01

    Changes in dynamic properties of mitochondria are increasingly implicated in neurodegenerative diseases, particularly Parkinson’s disease (PD). Static changes in mitochondrial morphology, often under acutely toxic conditions, are commonly utilized as indicators of changes in mitochondrial fission and fusion. However, in neurons, mitochondrial fission and fusion occur in a dynamic system of axonal/dendritic transport, biogenesis and degradation, and thus, likely interact and change over time. We sought to explore this using a chronic neuronal model (nonlethal low-concentration rotenone over several weeks), examining distal neurites, which may give insight into the earliest changes occurring in PD. Using this model, in live primary neurons, we directly quantified mitochondrial fission, fusion, and transport over time and integrated multiple aspects of mitochondrial dynamics, including morphology and growth/mitophagy. We found that rates of mitochondrial fission and fusion change as neurons age. In addition, we found that chronic rotenone exposure initially increased the ratio of fusion to fission, but later, this was reversed. Surprisingly, despite changes in rates of fission and fusion, mitochondrial morphology was minimally affected, demonstrating that morphology can be an inaccurate indicator of fission/fusion changes. In addition, we found evidence of subcellular compartmentalization of compensatory changes, as mitochondrial density increased in distal neurites first, which may be important in PD, where pathology may begin distally. We propose that rotenone-induced early changes such as in mitochondrial fusion are compensatory, accompanied later by detrimental fission. As evidence, in a dopaminergic neuronal model, in which chronic rotenone caused loss of neurites before cell death (like PD pathology), inhibiting fission protected against the neurite loss. This suggests that aberrant mitochondrial dynamics may contribute to the earliest neuropathologic

  9. Molecular Diagnosis of Tuberculosis.

    PubMed

    Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal

    2018-01-01

    Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.

  10. Influence of Molecular Shape on Molecular Orientation and Stability of Vapor-Deposited Organic Semiconductors

    NASA Astrophysics Data System (ADS)

    Walters, Diane M.; Johnson, Noah D.; Ediger, M. D.

    Physical vapor deposition is commonly used to prepare active layers in organic electronics. Recently, it has been shown that molecular orientation and packing can be tuned by changing the substrate temperature during deposition, while still producing macroscopically homogeneous films. These amorphous materials can be highly anisotropic when prepared with low substrate temperatures, and they can exhibit exceptional kinetic stability; films retain their favorable packing when heated to high temperatures. Here, we study the influence of molecular shape on molecular orientation and stability. We investigate disc-shaped molecules, such as TCTA and m-MTDATA, nearly spherical molecules, such as Alq3, and linear molecules covering a broad range of aspect ratios, such as p-TTP and BSB-Cz. Disc-shaped molecules have preferential horizontal orientation when deposited at low substrate temperatures, and their orientation can be tuned by changing the substrate temperature. Alq3 forms stable, amorphous films that are optically isotropic when vapor deposited over a broad range of substrate temperatures. This work may guide the choice of material and deposition conditions for vapor-deposited films used in organic electronics and allow for more efficient devices to be fabricated.

  11. From gene to structure: Lactobacillus bulgaricus D-lactate dehydrogenase from yogurt as an integrated curriculum model for undergraduate molecular biology and biochemistry laboratory courses.

    PubMed

    Lawton, Jeffrey A; Prescott, Noelle A; Lawton, Ping X

    2018-05-01

    We have developed an integrated, project-oriented curriculum for undergraduate molecular biology and biochemistry laboratory courses spanning two semesters that is organized around the ldhA gene from the yogurt-fermenting bacterium Lactobacillus bulgaricus, which encodes the enzyme d-lactate dehydrogenase. The molecular biology module, which consists of nine experiments carried out over eleven sessions, begins with the isolation of genomic DNA from L. bulgaricus in yogurt and guides students through the process of cloning the ldhA gene into a prokaryotic expression vector, followed by mRNA isolation and characterization of recombinant gene expression levels using RT-PCR. The biochemistry module, which consists of nine experiments carried out over eight sessions, begins with overexpression of the cloned ldhA gene and guides students through the process of affinity purification, biochemical characterization of the purified LdhA protein, and analysis of enzyme kinetics using various substrates and an inhibitor, concluding with a guided inquiry investigation of structure-function relationships in the three-dimensional structure of LdhA using molecular visualization software. Students conclude by writing a paper describing their work on the project, formatted as a manuscript to be submitted for publication in a scientific journal. Overall, this curriculum, with its emphasis on experiential learning, provides hands-on training with a variety of common laboratory techniques in molecular biology and biochemistry and builds experience with the process of scientific reasoning, along with reinforcement of essential transferrable skills such as critical thinking, information literacy, and written communication, all within the framework of an extended project having the look and feel of a research experience. © 2018 by The International Union of Biochemistry and Molecular Biology, 46(3):270-278, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

  12. Clinical Aspects of Idiopathic Inflammatory Bowel Disease: A Review for Pathologists.

    PubMed

    Lee, Hwajeong; Westerhoff, Maria; Shen, Bo; Liu, Xiuli

    2016-05-01

    -Idiopathic inflammatory bowel disease manifests with different clinical phenotypes showing varying behavior and risk for neoplasia. The clinical questions that are posed to pathologists differ depending on phase of the disease and the clinical circumstances. Understanding the clinical aspects of the dynamic disease process will enhance the role of pathology in optimizing the care of patients with inflammatory bowel disease. -To review clinical and surgical aspects of inflammatory bowel disease that are relevant to practicing pathologists. -The literature was reviewed. -Diagnosis and management of inflammatory bowel disease require an integrated evaluation of clinical, endoscopic, radiologic, and pathologic features. Therefore, close interaction between clinicians and pathologists is crucial. Having this team approach improves understanding of the pertinent clinical and surgical aspects of the disease and assists in the recognition of unusual presentation of variants, as well as mimics of idiopathic inflammatory bowel disease, by pathologists.

  13. Morphological, molecular and ecological aspects of the South American hypogeous fungi Alpova austroalnicola sp. nov.

    Treesearch

    Eduardo R. Nouhra; Laura S. Domínguez; Alejandra G. Becerra; James M. Trappe

    2005-01-01

    Field studies in Argentina's Yunga District revealed Alpova austroalnicola sp. nov., a hypogeous fungus associated with Alnus acuminata ssp, acuminata. Morphological and molecular studies based on amplification and sequencing of the nuclear LSU rDNA gene showed its unique identity within ...

  14. Integrating the Epistemic and Ontological Aspects of Content Knowledge in Science Teaching and Learning

    ERIC Educational Resources Information Center

    Papadouris, Nicos; Constantinou, Constantinos P.

    2017-01-01

    Promoting facility with content knowledge is one of the most important objectives of science teaching. Conventionally, the focus for this objective is placed on the substantive side of content knowledge (e.g. science concepts/laws), whereas its epistemic or ontological aspects (e.g. why do we construct concepts?) rarely receive explicit attention.…

  15. Integrative Medicine and Mood, Emotions and Mental Health.

    PubMed

    Shah, Anuj K; Becicka, Roman; Talen, Mary R; Edberg, Deborah; Namboodiri, Sreela

    2017-06-01

    An integrative approach to individuals with mood, emotional or mental health concerns involves a comprehensive model of care that is person-centered. Integrative medicine builds on a patient's personal meaning and goals (spiritual aspects) and includes herbal therapies, nutritional support, movement and physical manipulative therapies, mindfulness, relaxation strategies, and psychotherapies. Published by Elsevier Inc.

  16. Preparation, Purification, and Secondary Structure Determination of Bacillus Circulans Xylanase. A Molecular Laboratory Incorporating Aspects of Molecular Biology, Biochemistry, and Biophysical Chemistry

    ERIC Educational Resources Information Center

    Russo, Sal; Gentile, Lisa

    2006-01-01

    A project module designed for biochemistry or cellular and molecular biology student which involves determining the secondary structure of Bacillus circulans xylanase (BCX) by circular dichroism (CD) spectroscopy under conditions that compromise its stabilizing intramolecular forces is described. The lab model enhanced students knowledge of the…

  17. An integrated approach to fast and informative morphological vouchering of nematodes for applications in molecular barcoding

    PubMed Central

    De Ley, Paul; De Ley, Irma Tandingan; Morris, Krystalynne; Abebe, Eyualem; Mundo-Ocampo, Manuel; Yoder, Melissa; Heras, Joseph; Waumann, Dora; Rocha-Olivares, Axayácatl; Jay Burr, A.H; Baldwin, James G; Thomas, W. Kelley

    2005-01-01

    Molecular surveys of meiofaunal diversity face some interesting methodological challenges when it comes to interstitial nematodes from soils and sediments. Morphology-based surveys are greatly limited in processing speed, while barcoding approaches for nematodes are hampered by difficulties of matching sequence data with traditional taxonomy. Intermediate technology is needed to bridge the gap between both approaches. An example of such technology is video capture and editing microscopy, which consists of the recording of taxonomically informative multifocal series of microscopy images as digital video clips. The integration of multifocal imaging with sequence analysis of the D2D3 region of large subunit (LSU) rDNA is illustrated here in the context of a combined morphological and barcode sequencing survey of marine nematodes from Baja California and California. The resulting video clips and sequence data are made available online in the database NemATOL (http://nematol.unh.edu/). Analyses of 37 barcoded nematodes suggest that these represent at least 32 species, none of which matches available D2D3 sequences in public databases. The recorded multifocal vouchers allowed us to identify most specimens to genus, and will be used to match specimens with subsequent species identifications and descriptions of preserved specimens. Like molecular barcodes, multifocal voucher archives are part of a wider effort at structuring and changing the process of biodiversity discovery. We argue that data-rich surveys and phylogenetic tools for analysis of barcode sequences are an essential component of the exploration of phyla with a high fraction of undiscovered species. Our methods are also directly applicable to other meiofauna such as for example gastrotrichs and tardigrades. PMID:16214752

  18. Probing the brain with molecular fMRI.

    PubMed

    Ghosh, Souparno; Harvey, Peter; Simon, Jacob C; Jasanoff, Alan

    2018-06-01

    One of the greatest challenges of modern neuroscience is to incorporate our growing knowledge of molecular and cellular-scale physiology into integrated, organismic-scale models of brain function in behavior and cognition. Molecular-level functional magnetic resonance imaging (molecular fMRI) is a new technology that can help bridge these scales by mapping defined microscopic phenomena over large, optically inaccessible regions of the living brain. In this review, we explain how MRI-detectable imaging probes can be used to sensitize noninvasive imaging to mechanistically significant components of neural processing. We discuss how a combination of innovative probe design, advanced imaging methods, and strategies for brain delivery can make molecular fMRI an increasingly successful approach for spatiotemporally resolved studies of diverse neural phenomena, perhaps eventually in people. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. High-aspect ratio magnetic nanocomposite polymer cilium

    NASA Astrophysics Data System (ADS)

    Rahbar, M.; Tseng, H. Y.; Gray, B. L.

    2014-03-01

    This paper presents a new fabrication technique to achieve ultra high-aspect ratio artificial cilia micro-patterned from flexible highly magnetic rare earth nanoparticle-doped polymers. We have developed a simple, inexpensive and scalable fabrication method to create cilia structures that can be actuated by miniature electromagnets, that are suitable to be used for lab-on-a chip (LOC) and micro-total-analysis-system (μ-TAS) applications such as mixers and flow-control elements. The magnetic cilia are fabricated and magnetically polarized directly in microfluidic channels or reaction chambers, allowing for easy integration with complex microfluidic systems. These cilia structures can be combined on a single chip with other microfluidic components employing the same permanently magnetic nano-composite polymer (MNCP), such as valves or pumps. Rare earth permanent magnetic powder, (Nd0.7Ce0.3)10.5Fe83.9B5.6, is used to dope polydimethylsiloxane (PDMS), resulting in a highly flexible M-NCP of much higher magnetization and remanence [1] than ferromagnetic polymers typically employed in magnetic microfluidics. Sacrificial poly(ethylene-glycol) (PEG) is used to mold the highly magnetic polymer into ultra high-aspect ratio artificial cilia. Cilia structures with aspect ratio exceeding 8:0.13 can be easily fabricated using this technique and are actuated using miniature electromagnets to achieve a high range of motion/vibration.

  20. A national comparison of biochemistry and molecular biology capstone experiences.

    PubMed

    Aguanno, Ann; Mertz, Pamela; Martin, Debra; Bell, Ellis

    2015-01-01

    Recognizing the increasingly integrative nature of the molecular life sciences, the American Society for Biochemistry and Molecular Biology (ASBMB) recommends that Biochemistry and Molecular Biology (BMB) programs develop curricula based on concepts, content, topics, and expected student outcomes, rather than courses. To that end, ASBMB conducted a series of regional workshops to build a BMB Concept Inventory containing validated assessment tools, based on foundational and discipline-specific knowledge and essential skills, for the community to use. A culminating activity, which integrates the educational experience, is often part of undergraduate molecular life science programs. These "capstone" experiences are commonly defined as an attempt to measure student ability to synthesize and integrate acquired knowledge. However, the format, implementation, and approach to outcome assessment of these experiences are quite varied across the nation. Here we report the results of a nation-wide survey on BMB capstone experiences and discuss this in the context of published reports about capstones and the findings of the workshops driving the development of the BMB Concept Inventory. Both the survey results and the published reports reveal that, although capstone practices do vary, certain formats for the experience are used more frequently and similarities in learning objectives were identified. The use of rubrics to measure student learning is also regularly reported, but details about these assessment instruments are sparse in the literature and were not a focus of our survey. Finally, we outline commonalities in the current practice of capstones and suggest the next steps needed to elucidate best practices. © 2015 The International Union of Biochemistry and Molecular Biology.