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Sample records for accelerated biological function

  1. Menopause accelerates biological aging.

    PubMed

    Levine, Morgan E; Lu, Ake T; Chen, Brian H; Hernandez, Dena G; Singleton, Andrew B; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E; Quach, Austin; Kusters, Cynthia D J; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E; Widschwendter, Martin; Ritz, Beate R; Absher, Devin; Assimes, Themistocles L; Horvath, Steve

    2016-08-16

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  2. Accelerating scientific publication in biology

    PubMed Central

    Vale, Ronald D.

    2015-01-01

    Scientific publications enable results and ideas to be transmitted throughout the scientific community. The number and type of journal publications also have become the primary criteria used in evaluating career advancement. Our analysis suggests that publication practices have changed considerably in the life sciences over the past 30 years. More experimental data are now required for publication, and the average time required for graduate students to publish their first paper has increased and is approaching the desirable duration of PhD training. Because publication is generally a requirement for career progression, schemes to reduce the time of graduate student and postdoctoral training may be difficult to implement without also considering new mechanisms for accelerating communication of their work. The increasing time to publication also delays potential catalytic effects that ensue when many scientists have access to new information. The time has come for life scientists, funding agencies, and publishers to discuss how to communicate new findings in a way that best serves the interests of the public and the scientific community. PMID:26508643

  3. Accelerating scientific publication in biology.

    PubMed

    Vale, Ronald D

    2015-11-01

    Scientific publications enable results and ideas to be transmitted throughout the scientific community. The number and type of journal publications also have become the primary criteria used in evaluating career advancement. Our analysis suggests that publication practices have changed considerably in the life sciences over the past 30 years. More experimental data are now required for publication, and the average time required for graduate students to publish their first paper has increased and is approaching the desirable duration of PhD training. Because publication is generally a requirement for career progression, schemes to reduce the time of graduate student and postdoctoral training may be difficult to implement without also considering new mechanisms for accelerating communication of their work. The increasing time to publication also delays potential catalytic effects that ensue when many scientists have access to new information. The time has come for life scientists, funding agencies, and publishers to discuss how to communicate new findings in a way that best serves the interests of the public and the scientific community. PMID:26508643

  4. Next generation tools to accelerate the synthetic biology process.

    PubMed

    Shih, Steve C C; Moraes, Christopher

    2016-05-16

    Synthetic biology follows the traditional engineering paradigm of designing, building, testing and learning to create new biological systems. While such approaches have enormous potential, major challenges still exist in this field including increasing the speed at which this workflow can be performed. Here, we present recently developed microfluidic tools that can be used to automate the synthetic biology workflow with the goal of advancing the likelihood of producing desired functionalities. With the potential for programmability, automation, and robustness, the integration of microfluidics and synthetic biology has the potential to accelerate advances in areas such as bioenergy, health, and biomaterials. PMID:27146265

  5. Functions in Biological Kind Classification

    ERIC Educational Resources Information Center

    Lombrozo, Tania; Rehder, Bob

    2012-01-01

    Biological traits that serve functions, such as a zebra's coloration (for camouflage) or a kangaroo's tail (for balance), seem to have a special role in conceptual representations for biological kinds. In five experiments, we investigate whether and why functional features are privileged in biological kind classification. Experiment 1…

  6. The relativity of biological function.

    PubMed

    Laubichler, Manfred D; Stadler, Peter F; Prohaska, Sonja J; Nowick, Katja

    2015-12-01

    Function is a central concept in biological theories and explanations. Yet discussions about function are often based on a narrow understanding of biological systems and processes, such as idealized molecular systems or simple evolutionary, i.e., selective, dynamics. Conflicting conceptions of function continue to be used in the scientific literature to support certain claims, for instance about the fraction of "functional DNA" in the human genome. Here we argue that all biologically meaningful interpretations of function are necessarily context dependent. This implies that they derive their meaning as well as their range of applicability only within a specific theoretical and measurement context. We use this framework to shed light on the current debate about functional DNA and argue that without considering explicitly the theoretical and measurement contexts all attempts to integrate biological theories are prone to fail. PMID:26449352

  7. Accelerating Yeast Prion Biology using Droplet Microfluidics

    NASA Astrophysics Data System (ADS)

    Ung, Lloyd; Rotem, Assaf; Jarosz, Daniel; Datta, Manoshi; Lindquist, Susan; Weitz, David

    2012-02-01

    Prions are infectious proteins in a misfolded form, that can induce normal proteins to take the misfolded state. Yeast prions are relevant, as a model of human prion diseases, and interesting from an evolutionary standpoint. Prions may also be a form of epigenetic inheritance, which allow yeast to adapt to stressful conditions at rates exceeding those of random mutations and propagate that adaptation to their offspring. Encapsulation of yeast in droplet microfluidic devices enables high-throughput measurements with single cell resolution, which would not be feasible using bulk methods. Millions of populations of yeast can be screened to obtain reliable measurements of prion induction and loss rates. The population dynamics of clonal yeast, when a fraction of the cells are prion expressing, can be elucidated. Furthermore, the mechanism by which certain strains of bacteria induce yeast to express prions in the wild can be deduced. Integrating the disparate fields of prion biology and droplet microfluidics reveals a more complete picture of how prions may be more than just diseases and play a functional role in yeast.

  8. Biological assessments for the low energy demonstration accelerator, 1996

    SciTech Connect

    Cross, S.

    1997-03-01

    This report discusses the biological impact to the area around the Los Alamos National Laboratory of the Low Energy Demonstration Accelerator. In particular the impact to the soils, water quality, vegetation, and wildlife are discussed.

  9. The biological function of consciousness

    PubMed Central

    Earl, Brian

    2014-01-01

    This research is an investigation of whether consciousness—one's ongoing experience—influences one's behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1) contrary to one's intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2) consciousness does have a biological function; and (3) consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM) for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc.) are incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness. PMID:25140159

  10. Functional Aspects of Biological Networks

    NASA Astrophysics Data System (ADS)

    Sneppen, Kim

    2007-03-01

    We discuss biological networks with respect to 1) relative positioning and importance of high degree nodes, 2) function and signaling, 3) logic and dynamics of regulation. Visually the soft modularity of many real world networks can be characterized in terms of number of high and low degrees nodes positioned relative to each other in a landscape analogue with mountains (high-degree nodes) and valleys (low-degree nodes). In these terms biological networks looks like rugged landscapes with separated peaks, hub proteins, which each are roughly as essential as any of the individual proteins on the periphery of the hub. Within each sup-domain of a molecular network one can often identify dynamical feedback mechanisms that falls into combinations of positive and negative feedback circuits. We will illustrate this with examples taken from phage regulation and bacterial uptake and regulation of small molecules. In particular we find that a double negative regulation often are replaced by a single positive link in unrelated organisms with same functional requirements. Overall we argue that network topology primarily reflects functional constraints. References: S. Maslov and K. Sneppen. ``Computational architecture of the yeast regulatory network." Phys. Biol. 2:94 (2005) A. Trusina et al. ``Functional alignment of regulatory networks: A study of temerate phages". Plos Computational Biology 1:7 (2005). J.B. Axelsen et al. ``Degree Landscapes in Scale-Free Networks" physics/0512075 (2005). A. Trusina et al. ``Hierarchy and Anti-Hierarchy in Real and Scale Free networks." PRL 92:178702 (2004) S. Semsey et al. ``Genetic Regulation of Fluxes: Iron Homeostasis of Escherichia coli". (2006) q-bio.MN/0609042

  11. Accelerating functional verification of an integrated circuit

    SciTech Connect

    Deindl, Michael; Ruedinger, Jeffrey Joseph; Zoellin, Christian G.

    2015-10-27

    Illustrative embodiments include a method, system, and computer program product for accelerating functional verification in simulation testing of an integrated circuit (IC). Using a processor and a memory, a serial operation is replaced with a direct register access operation, wherein the serial operation is configured to perform bit shifting operation using a register in a simulation of the IC. The serial operation is blocked from manipulating the register in the simulation of the IC. Using the register in the simulation of the IC, the direct register access operation is performed in place of the serial operation.

  12. Biocellion: accelerating computer simulation of multicellular biological system models

    PubMed Central

    Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

    2014-01-01

    Motivation: Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. Results: We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Availability and implementation: Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. Contact: seunghwa.kang@pnnl.gov PMID:25064572

  13. GPU accelerated dynamic functional connectivity analysis for functional MRI data.

    PubMed

    Akgün, Devrim; Sakoğlu, Ünal; Esquivel, Johnny; Adinoff, Bryon; Mete, Mutlu

    2015-07-01

    Recent advances in multi-core processors and graphics card based computational technologies have paved the way for an improved and dynamic utilization of parallel computing techniques. Numerous applications have been implemented for the acceleration of computationally-intensive problems in various computational science fields including bioinformatics, in which big data problems are prevalent. In neuroimaging, dynamic functional connectivity (DFC) analysis is a computationally demanding method used to investigate dynamic functional interactions among different brain regions or networks identified with functional magnetic resonance imaging (fMRI) data. In this study, we implemented and analyzed a parallel DFC algorithm based on thread-based and block-based approaches. The thread-based approach was designed to parallelize DFC computations and was implemented in both Open Multi-Processing (OpenMP) and Compute Unified Device Architecture (CUDA) programming platforms. Another approach developed in this study to better utilize CUDA architecture is the block-based approach, where parallelization involves smaller parts of fMRI time-courses obtained by sliding-windows. Experimental results showed that the proposed parallel design solutions enabled by the GPUs significantly reduce the computation time for DFC analysis. Multicore implementation using OpenMP on 8-core processor provides up to 7.7× speed-up. GPU implementation using CUDA yielded substantial accelerations ranging from 18.5× to 157× speed-up once thread-based and block-based approaches were combined in the analysis. Proposed parallel programming solutions showed that multi-core processor and CUDA-supported GPU implementations accelerated the DFC analyses significantly. Developed algorithms make the DFC analyses more practical for multi-subject studies with more dynamic analyses. PMID:25805449

  14. Integrating Functional, Developmental and Evolutionary Biology into Biology Curricula

    ERIC Educational Resources Information Center

    Haave, Neil

    2012-01-01

    A complete understanding of life involves how organisms are able to function in their environment and how they arise. Understanding how organisms arise involves both their evolution and development. Thus to completely comprehend living things, biology must study their function, development and evolution. Previous proposals for standardized…

  15. Functional Translational Readthrough: A Systems Biology Perspective.

    PubMed

    Schueren, Fabian; Thoms, Sven

    2016-08-01

    Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries. PMID:27490485

  16. Functional Translational Readthrough: A Systems Biology Perspective

    PubMed Central

    Schueren, Fabian

    2016-01-01

    Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries. PMID:27490485

  17. Metacognition: computation, biology and function.

    PubMed

    Fleming, Stephen M; Dolan, Raymond J; Frith, Christopher D

    2012-05-19

    Many complex systems maintain a self-referential check and balance. In animals, such reflective monitoring and control processes have been grouped under the rubric of metacognition. In this introductory article to a Theme Issue on metacognition, we review recent and rapidly progressing developments from neuroscience, cognitive psychology, computer science and philosophy of mind. While each of these areas is represented in detail by individual contributions to the volume, we take this opportunity to draw links between disciplines, and highlight areas where further integration is needed. Specifically, we cover the definition, measurement, neurobiology and possible functions of metacognition, and assess the relationship between metacognition and consciousness. We propose a framework in which level of representation, order of behaviour and access consciousness are orthogonal dimensions of the conceptual landscape. PMID:22492746

  18. Metacognition: computation, biology and function

    PubMed Central

    Fleming, Stephen M.; Dolan, Raymond J.; Frith, Christopher D.

    2012-01-01

    Many complex systems maintain a self-referential check and balance. In animals, such reflective monitoring and control processes have been grouped under the rubric of metacognition. In this introductory article to a Theme Issue on metacognition, we review recent and rapidly progressing developments from neuroscience, cognitive psychology, computer science and philosophy of mind. While each of these areas is represented in detail by individual contributions to the volume, we take this opportunity to draw links between disciplines, and highlight areas where further integration is needed. Specifically, we cover the definition, measurement, neurobiology and possible functions of metacognition, and assess the relationship between metacognition and consciousness. We propose a framework in which level of representation, order of behaviour and access consciousness are orthogonal dimensions of the conceptual landscape. PMID:22492746

  19. DNASU plasmid and PSI:Biology-Materials repositories: resources to accelerate biological research

    PubMed Central

    Seiler, Catherine Y.; Park, Jin G.; Sharma, Amit; Hunter, Preston; Surapaneni, Padmini; Sedillo, Casey; Field, James; Algar, Rhys; Price, Andrea; Steel, Jason; Throop, Andrea; Fiacco, Michael; LaBaer, Joshua

    2014-01-01

    The mission of the DNASU Plasmid Repository is to accelerate research by providing high-quality, annotated plasmid samples and online plasmid resources to the research community through the curated DNASU database, website and repository (http://dnasu.asu.edu or http://dnasu.org). The collection includes plasmids from grant-funded, high-throughput cloning projects performed in our laboratory, plasmids from external researchers, and large collections from consortia such as the ORFeome Collaboration and the NIGMS-funded Protein Structure Initiative: Biology (PSI:Biology). Through DNASU, researchers can search for and access detailed information about each plasmid such as the full length gene insert sequence, vector information, associated publications, and links to external resources that provide additional protein annotations and experimental protocols. Plasmids can be requested directly through the DNASU website. DNASU and the PSI:Biology-Materials Repositories were previously described in the 2010 NAR Database Issue (Cormier, C.Y., Mohr, S.E., Zuo, D., Hu, Y., Rolfs, A., Kramer, J., Taycher, E., Kelley, F., Fiacco, M., Turnbull, G. et al. (2010) Protein Structure Initiative Material Repository: an open shared public resource of structural genomics plasmids for the biological community. Nucleic Acids Res., 38, D743–D749.). In this update we will describe the plasmid collection and highlight the new features in the website redesign, including new browse/search options, plasmid annotations and a dynamic vector mapping feature that was developed in collaboration with LabGenius. Overall, these plasmid resources continue to enable research with the goal of elucidating the role of proteins in both normal biological processes and disease. PMID:24225319

  20. Structure and Associated Biological Functions of Viroids.

    PubMed

    Steger, Gerhard; Perreault, Jean-Pierre

    2016-01-01

    Mature viroids consist of a noncoding, covalently closed circular RNA that is able to autonomously infect respective host plants. Thus, they must utilize proteins of the host for most biological functions such as replication, processing, transport, and pathogenesis. Therefore, viroids can be regarded as minimal parasites of the host machinery. They have to present to the host machinery the appropriate signals based on either their sequence or their structure. Here, we summarize such sequence and structural features critical for the biological functions of viroids. PMID:26997592

  1. Low-energy dynamics and biological function

    NASA Astrophysics Data System (ADS)

    Lechner, R. E.; Fitter, J.; Dencher, N. A.; Hauß, T.

    2006-11-01

    Results from QENS experiments using a resolution of 93 μeV on a biological system are reported. The photocycle of the proton pump bacteriorhodopsin (BR) is known to slow down with decreasing temperature and humidity, a behaviour related to the ‘dynamic transition’. We have achieved a separation of the pure thermal activation effect involving the plasticizing action of hydration water, from effects due to the variation of the hydration level on the dynamics of purple membrane (PM) with its integral protein BR, and have correlated this with its ability to function. This demonstrates that the biological function of BR requires molecular dynamics in the ps range.

  2. [Biological functions of tin and disease].

    PubMed

    Arakawa, Yasuaki; Tomiyama, Kenichi

    2016-07-01

    Tin generates a wide variety of biological functions due to its chemical character. In this article, the modes of the biological functions of tin(especially organotin compounds) are reviewed, with special emphasis on the connection with the immune system, brain nervous system and endocrine system, on the basis of our data. To sum up this article, the biological functions of organotin compounds appear to be due to the following several processes: (1) their incorporation into the cells in vesicle form through fusion or in a similar manner to their incorporation in cationic form; (2) transport to and accumulation in the regions of the Golgi apparatus and endoplasmic reticulum (ER), but not to or in the plasma membrane or nucleus because of their hydrophobicity; (3) inhibition of intracellular phospholipid transport between organelles due to impairment of the structures and functions of the Golgi apparatus and ER; (4) inhibition of the membrane-mediated signal transduction system leading to DNA synthesis via phospholipid turnover and Ca2+ mobilization, as in cell proliferation systems; (5) disturbance of the trace element balance and the localization of certain elements; (6) disorders of membrane-mediated Ca2+ homeostasis via various channel functions including Zn modulation on the plasma and organelle membranes, and protein phosphorylation, as in the signal transduction systems of memory and olfaction; (7) necrosis or apoptosis in vivo or toxic cell death in vitro. PMID:27455812

  3. Biological cluster evaluation for gene function prediction.

    PubMed

    Klie, Sebastian; Nikoloski, Zoran; Selbig, Joachim

    2014-06-01

    Recent advances in high-throughput omics techniques render it possible to decode the function of genes by using the "guilt-by-association" principle on biologically meaningful clusters of gene expression data. However, the existing frameworks for biological evaluation of gene clusters are hindered by two bottleneck issues: (1) the choice for the number of clusters, and (2) the external measures which do not take in consideration the structure of the analyzed data and the ontology of the existing biological knowledge. Here, we address the identified bottlenecks by developing a novel framework that allows not only for biological evaluation of gene expression clusters based on existing structured knowledge, but also for prediction of putative gene functions. The proposed framework facilitates propagation of statistical significance at each of the following steps: (1) estimating the number of clusters, (2) evaluating the clusters in terms of novel external structural measures, (3) selecting an optimal clustering algorithm, and (4) predicting gene functions. The framework also includes a method for evaluation of gene clusters based on the structure of the employed ontology. Moreover, our method for obtaining a probabilistic range for the number of clusters is demonstrated valid on synthetic data and available gene expression profiles from Saccharomyces cerevisiae. Finally, we propose a network-based approach for gene function prediction which relies on the clustering of optimal score and the employed ontology. Our approach effectively predicts gene function on the Saccharomyces cerevisiae data set and is also employed to obtain putative gene functions for an Arabidopsis thaliana data set. PMID:20059365

  4. Phenological response of a key ecosystem function to biological invasion.

    PubMed

    Alp, Maria; Cucherousset, Julien; Buoro, Mathieu; Lecerf, Antoine

    2016-05-01

    Although climate warming has been widely demonstrated to induce shifts in the timing of many biological events, the phenological consequences of other prominent global change drivers remain largely unknown. Here, we investigated the effects of biological invasions on the seasonality of leaf litter decomposition, a crucial freshwater ecosystem function. Decomposition rates were quantified in 18 temperate shallow lakes distributed along a gradient of crayfish invasion and a temperature-based model was constructed to predict yearly patterns of decomposition. We found that, through direct detritus consumption, omnivorous invasive crayfish accelerated decomposition rates up to fivefold in spring, enhancing temperature dependence of the process and shortening the period of major detritus availability in the ecosystem by up to 39 days (95% CI: 15-61). The fact that our estimates are an order of magnitude higher than any previously reported climate-driven phenological shifts indicates that some powerful drivers of phenological change have been largely overlooked. PMID:26931804

  5. Functional Error Models to Accelerate Nested Sampling

    NASA Astrophysics Data System (ADS)

    Josset, L.; Elsheikh, A. H.; Demyanov, V.; Lunati, I.

    2014-12-01

    The main challenge in groundwater problems is the reliance on large numbers of unknown parameters with wide rage of associated uncertainties. To translate this uncertainty to quantities of interest (for instance the concentration of pollutant in a drinking well), a large number of forward flow simulations is required. To make the problem computationally tractable, Josset et al. (2013, 2014) introduced the concept of functional error models. It consists in two elements: a proxy model that is cheaper to evaluate than the full physics flow solver and an error model to account for the missing physics. The coupling of the proxy model and the error models provides reliable predictions that approximate the full physics model's responses. The error model is tailored to the problem at hand by building it for the question of interest. It follows a typical approach in machine learning where both the full physics and proxy models are evaluated for a training set (subset of realizations) and the set of responses is used to construct the error model using functional data analysis. Once the error model is devised, a prediction of the full physics response for a new geostatistical realization can be obtained by computing the proxy response and applying the error model. We propose the use of functional error models in a Bayesian inference context by combining it to the Nested Sampling (Skilling 2006; El Sheikh et al. 2013, 2014). Nested Sampling offers a mean to compute the Bayesian Evidence by transforming the multidimensional integral into a 1D integral. The algorithm is simple: starting with an active set of samples, at each iteration, the sample with the lowest likelihood is kept aside and replaced by a sample of higher likelihood. The main challenge is to find this sample of higher likelihood. We suggest a new approach: first the active set is sampled, both proxy and full physics models are run and the functional error model is build. Then, at each iteration of the Nested

  6. Catch bonds: physical models and biological functions.

    PubMed

    Zhu, Cheng; McEver, Rodger P

    2005-09-01

    Force can shorten the lifetimes of receptor-ligand bonds by accelerating their dissociation. Perhaps paradoxical at first glance, bond lifetimes can also be prolonged by force. This counterintuitive behavior was named catch bonds, which is in contrast to the ordinary slip bonds that describe the intuitive behavior of lifetimes being shortened by force. Fifteen years after their theoretical proposal, catch bonds have finally been observed. In this article we review recently published data that have demonstrated catch bonds in the selectin system and suggested catch bonds in other systems, the theoretical models for their explanations, and their function as a mechanism for flow-enhanced adhesion. PMID:16708472

  7. Aegerolysins: Structure, function, and putative biological role

    PubMed Central

    Berne, Sabina; Lah, Ljerka; Sepčić, Kristina

    2009-01-01

    Aegerolysins, discovered in fungi, bacteria and plants, are highly similar proteins with interesting biological properties. Certain aegerolysins possess antitumoral, antiproliferative, and antibacterial activities. Further possible medicinal applications include their use in the prevention of atherosclerosis, or as vaccines. Additional biotechnological value of fungal aegerolysins lies in their involvement in development, which could improve cultivation of commercially important edible mushrooms. Besides, new insights on microheterogeneity of raft-like membrane domains could be gained by using aegerolysins as specific markers in cell and molecular biology. Although the exact function of aegerolysins in their producing organisms remains to be explained, they are biochemically well characterized all-β structured proteins sharing the following common features: low isoelectric points, similar molecular weights (15–17 kDa), and stability in a wide pH range. PMID:19309687

  8. Source Time Function of P-wave Acceleration

    NASA Astrophysics Data System (ADS)

    Chen, K. J.

    2015-12-01

    In this study, the site effect of time function of the Taiwan area will be invested. The recorded response function of a single earthquake will be calculated by Complex Demodulation. The path effect of each event-station pair will be estimated by using the forward method with a 3-D attenuation structure. After removing the path effect, the source frequency function of each single event will be obtained by averaging the whole station gotten. Using this source time function to calculate the path effect of the all stations, the theoretic received time frequency function can be obtained. The difference between this theoretic function and the recorded function is the site effect function of the single station. The characterics of the site effect in Taiwan area will be analyzed. Recalculate the path effect and remove the site effect of each station to get the new source time function of P-wave acceleration.

  9. Leg joint function during walking acceleration and deceleration.

    PubMed

    Qiao, Mu; Jindrich, Devin L

    2016-01-01

    Although constant-average-velocity walking has been extensively studied, less is known about walking maneuvers that change speed. We investigated the function of individual leg joints when humans walked at a constant speed, accelerated or decelerated. We hypothesized that leg joints make different functional contributions to maneuvers. Specifically, we hypothesized that the hip generates positive mechanical work (acting like a "motor"), the knee generates little mechanical work (acting like a "strut"), and the ankle absorbs energy during the first half of stance and generates energy during the second half (consistent with "spring"-like function). We recorded full body kinematics and kinetics, used inverse dynamics to estimate net joint moments, and decomposed joint function into strut-, motor-, damper-, and spring-like components using indices based on net joint work. Although overall leg mechanics were primarily strut-like, individual joints did not act as struts during stance. The hip functioned as a power generating "motor," and ankle function was consistent with spring-like behavior. Even though net knee work was small, the knee did not behave solely as a strut but also showed motor-, and damper-like function. Acceleration involved increased motor-like function of the hip and ankle. Deceleration involved decreased hip motor-like function and ankle spring-like function and increased damping at the knee and ankle. Changes to joint mechanical work were primarily due to changes in joint angular displacements and not net moments. Overall, joints maintain different functional roles during unsteady locomotion. PMID:26686397

  10. Acceleration of reverse analysis method using hyperbolic activation function

    NASA Astrophysics Data System (ADS)

    Pwasong, Augustine; Sathasivam, Saratha

    2015-10-01

    Hyperbolic activation function is examined for its ability to accelerate the performance of doing data mining by using a technique named as Reverse Analysis method. In this paper, we describe how Hopfield network perform better with hyperbolic activation function and able to induce logical rules from large database by using reverse analysis method: given the values of the connections of a network, we can hope to know what logical rules are entrenched in the database. We limit our analysis to Horn clauses.

  11. Biological dose volume histograms during conformal hypofractionated accelerated radiotherapy for prostate cancer

    SciTech Connect

    Koukourakis, Michael I.; Abatzoglou, Ioannis; Touloupidis, Stavros; Manavis, Ioannis

    2007-01-15

    Radiobiological data suggest that prostate cancer has a low {alpha}/{beta} ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of 2.7 Gy, while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of 0.7 Gy. Radiotherapy is accomplished within 19 days (15 fractions). Dose volume histograms, calculated for tissue specific {alpha}/{beta} ratios and time factors, predict a high biological dose to the prostate and seminal vesicles (77-93 Gy). The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues.

  12. Flavonoids: biosynthesis, biological functions, and biotechnological applications

    PubMed Central

    Falcone Ferreyra, María L.; Rius, Sebastián P.; Casati, Paula

    2012-01-01

    Flavonoids are widely distributed secondary metabolites with different metabolic functions in plants. The elucidation of the biosynthetic pathways, as well as their regulation by MYB, basic helix-loop-helix (bHLH), and WD40-type transcription factors, has allowed metabolic engineering of plants through the manipulation of the different final products with valuable applications. The present review describes the regulation of flavonoid biosynthesis, as well as the biological functions of flavonoids in plants, such as in defense against UV-B radiation and pathogen infection, nodulation, and pollen fertility. In addition, we discuss different strategies and achievements through the genetic engineering of flavonoid biosynthesis with implication in the industry and the combinatorial biosynthesis in microorganisms by the reconstruction of the pathway to obtain high amounts of specific compounds. PMID:23060891

  13. Aluminum-26 as a biological tracer using accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Flarend, Richard Edward

    1997-06-01

    The development of accelerator mass spectrometry (AMS) has provided a practical method of detection for the only isotope of aluminum suitable as a tracer, 26Al. The use of 26Al as a tracer for aluminum has made possible the study of aluminum metabolism and the pharmacokinetics of aluminum-containing drugs at physiological levels. An overview of the various advantages of using 26Al as a tracer for aluminum and a general description of the AMS technique as applied to bio-medical applications is given. To illustrate the versatility of 26Al as a tracer for aluminum, 26Al studies of the past several years are discussed briefly. In addition, Two novel investigations dealing with 26Al-labeled drugs will be presented in more detail. In one of these studies, it was found that 26Al from aluminum hydroxide and aluminum phosphate vaccine adjuvants appeared in the blood just one hour after intramuscular injection. This is a surprising result since the currently held theory of how adjuvants work assumes that adjuvants remain insoluble and hold the antigen at the injection site for a long period of time. In another project, 26Al-labeled antiperspirants are being characterized by combining AMS with traditional analytical and chromatographic techniques. Future directions for this and other possible studies are discussed.

  14. Transcription factor binding energy vs. biological function

    NASA Astrophysics Data System (ADS)

    Djordjevic, M.; Grotewold, E.

    2007-03-01

    Transcription factors (TFs) are proteins that bind to DNA and regulate expression of genes. Identification of transcription factor binding sites within the regulatory segments of genomic DNA is an important step towards understanding of gene regulatory networks. Recent theoretical advances that we developed [1,2], allow us to infer TF-DNA interaction parameters from in-vitro selection experiments [3]. We use more than 6000 binding sequences [3], assembled under controlled conditions, to obtain protein-DNA interaction parameters for a mammalian TF with up to now unprecedented accuracy. Can one accurately identify biologically functional TF binding sites (i.e. the binding sites that regulate gene expression), even with the best possible protein-DNA interaction parameters? To address this issue we i) compare our prediction of protein binding with gene expression data, ii) use evolutionary comparison between related mammalian genomes. Our results strongly suggest that in a genome there exists a large number of randomly occurring high energy binding sites that are not biologically functional. [1] M Djordjevic, submitted to Biomol. Eng. [2] M. Djordjevic and A. M. Sengupta, Phys. Biol. 3: 13, 2006. [3] E. Roulet et al., Nature Biotech. 20: 831, 2002.

  15. Accelerated MRI for the assessment of cardiac function.

    PubMed

    Axel, Leon; Otazo, Ricardo

    2016-07-01

    Heart disease is a worldwide public health problem; assessment of cardiac function is an important part of the diagnosis and management of heart disease. MRI of the heart can provide clinically useful information on cardiac function, although it is still not routinely used in clinical practice, in part because of limited imaging speed. New accelerated methods for performing cardiovascular MRI (CMR) have the potential to provide both increased imaging speed and robustness to CMR, as well as access to increased functional information. In this review, we will briefly discuss the main methods currently employed to accelerate CMR methods, such as parallel imaging, k-t undersampling and compressed sensing, as well as new approaches that extend the idea of compressed sensing and exploit sparsity to provide richer information of potential use in clinical practice. PMID:27033471

  16. Accelerating Cancer Systems Biology Research through Semantic Web Technology

    PubMed Central

    Wang, Zhihui; Sagotsky, Jonathan; Taylor, Thomas; Shironoshita, Patrick; Deisboeck, Thomas S.

    2012-01-01

    Cancer systems biology is an interdisciplinary, rapidly expanding research field in which collaborations are a critical means to advance the field. Yet the prevalent database technologies often isolate data rather than making it easily accessible. The Semantic Web has the potential to help facilitate web-based collaborative cancer research by presenting data in a manner that is self-descriptive, human and machine readable, and easily sharable. We have created a semantically linked online Digital Model Repository (DMR) for storing, managing, executing, annotating, and sharing computational cancer models. Within the DMR, distributed, multidisciplinary, and inter-organizational teams can collaborate on projects, without forfeiting intellectual property. This is achieved by the introduction of a new stakeholder to the collaboration workflow, the institutional licensing officer, part of the Technology Transfer Office. Furthermore, the DMR has achieved silver level compatibility with the National Cancer Institute’s caBIG®, so users can not only interact with the DMR through a web browser but also through a semantically annotated and secure web service. We also discuss the technology behind the DMR leveraging the Semantic Web, ontologies, and grid computing to provide secure inter-institutional collaboration on cancer modeling projects, online grid-based execution of shared models, and the collaboration workflow protecting researchers’ intellectual property. PMID:23188758

  17. Accelerating cancer systems biology research through Semantic Web technology.

    PubMed

    Wang, Zhihui; Sagotsky, Jonathan; Taylor, Thomas; Shironoshita, Patrick; Deisboeck, Thomas S

    2013-01-01

    Cancer systems biology is an interdisciplinary, rapidly expanding research field in which collaborations are a critical means to advance the field. Yet the prevalent database technologies often isolate data rather than making it easily accessible. The Semantic Web has the potential to help facilitate web-based collaborative cancer research by presenting data in a manner that is self-descriptive, human and machine readable, and easily sharable. We have created a semantically linked online Digital Model Repository (DMR) for storing, managing, executing, annotating, and sharing computational cancer models. Within the DMR, distributed, multidisciplinary, and inter-organizational teams can collaborate on projects, without forfeiting intellectual property. This is achieved by the introduction of a new stakeholder to the collaboration workflow, the institutional licensing officer, part of the Technology Transfer Office. Furthermore, the DMR has achieved silver level compatibility with the National Cancer Institute's caBIG, so users can interact with the DMR not only through a web browser but also through a semantically annotated and secure web service. We also discuss the technology behind the DMR leveraging the Semantic Web, ontologies, and grid computing to provide secure inter-institutional collaboration on cancer modeling projects, online grid-based execution of shared models, and the collaboration workflow protecting researchers' intellectual property. PMID:23188758

  18. Biological Effectiveness of Accelerated Protons for Chromosome Exchanges

    PubMed Central

    George, Kerry A.; Hada, Megumi; Cucinotta, Francis A.

    2015-01-01

    We have investigated chromosome exchanges induced in human cells by seven different energies of protons (5–2500 MeV) with LET values ranging from 0.2 to 8 keV/μm. Human lymphocytes were irradiated in vitro and chromosome damage was assessed using three-color fluorescence in situ hybridization chromosome painting in chemically condensed chromosomes collected during the first cell division post irradiation. The relative biological effectiveness (RBE) was calculated from the initial slope of the dose–response curve for chromosome exchanges with respect to low dose and low dose-rate γ-rays (denoted as RBEmax), and relative to acute doses of γ-rays (denoted as RBEγAcute). The linear dose–response term was similar for all energies of protons, suggesting that the decrease in LET with increasing proton energy was balanced by the increase in dose from the production of nuclear secondaries. Secondary particles increase slowly above energies of a few hundred megaelectronvolts. Additional studies of 50 g/cm2 aluminum shielded high-energy proton beams showed minor differences compared to the unshielded protons and lower RBE values found for shielded in comparison to unshielded beams of 2 or 2.5 GeV. All energies of protons produced a much higher percentage of complex-type chromosome exchanges when compared to acute doses of γ-rays. The implications of these results for space radiation protection and proton therapy are discussed. PMID:26539409

  19. Biological and medical research with accelerated heavy ions at the Bevalac, 1977-1980. [Lead abstract

    SciTech Connect

    Pirruccello, M.C.; Tobias, C.A.

    1980-11-01

    Separate abstracts were prepared for the 46 papers presented in this progress report. This report is a major review of studies with accelerated heavy ions carried out by the Biology and Medicine Division of Lawrence Berkeley Laboratory from 1977 to 1980. (KRM)

  20. Particle Accelerator Applications: Ion and Electron Irradiation in Materials Science, Biology and Medicine

    NASA Astrophysics Data System (ADS)

    Rodríguez-Fernández, Luis

    2010-09-01

    Although the developments of particle accelerators are devoted to basic study of matter constituents, since the beginning these machines have been applied with different purposes in many areas also. Today particle accelerators are essential instruments for science and technology. This work presents an overview of the main application for direct particle irradiation with accelerator in material science, biology and medicine. They are used for material synthesis by ion implantation and charged particle irradiation; to make coatings and micromachining; to characterize broad kind of samples by ion beam analysis techniques; as mass spectrometers for atomic isotopes determination. In biomedicine the accelerators are applied for the study of effects by charged particles on cells. In medicine the radiotherapy by electron irradiation is widely used, while hadrontherapy is still under development. Also, they are necessary for short life radioisotopes production required in radiodiagnostic.

  1. Frameworks for programming biological function through RNA parts and devices

    PubMed Central

    Win, Maung Nyan; Liang, Joe C.; Smolke, Christina D.

    2009-01-01

    One of the long-term goals of synthetic biology is to reliably engineer biological systems that perform human-defined functions. Currently, researchers face several scientific and technical challenges in designing and building biological systems, one of which is associated with our limited ability to access, transmit, and control molecular information through the design of functional biomolecules exhibiting novel properties. The fields of RNA biology and nucleic acid engineering, along with the tremendous interdisciplinary growth of synthetic biology, are fueling advances in the emerging field of RNA programming in living systems. Researchers are designing functional RNA molecules that exhibit increasingly complex functions and integrating these molecules into cellular circuits to program higher-level biological functions. The continued integration and growth of RNA design and synthetic biology presents exciting potential to transform how we interact with and program biology. PMID:19318211

  2. Biological shield design and analysis of KIPT accelerator-driven subcritical facility.

    SciTech Connect

    Zhong, Z.; Gohar, Y.; Nuclear Engineering Division

    2009-12-01

    Argonne National Laboratory of the United States and Kharkov Institute of Physics and Technology of Ukraine have been collaborating on the conceptual design development of an electron accelerator-driven subcritical facility. The facility will be utilized for performing basic and applied nuclear research, producing medical isotopes, and training young nuclear specialists. This paper presents the design and analyses of the biological shield performed for the top section of the facility. The neutron source driving the subcritical assembly is generated from the interaction of a 100-kW electron beam with a natural uranium target. The electron energy is in the range of 100 to 200 MeV, and it has a uniform spatial distribution. The shield design and the associated analyses are presented including different parametric studies. In the analyses, a significant effort was dedicated to the accurate prediction of the radiation dose outside the shield boundary as a function of the shield thickness without geometrical approximations or material homogenization. The MCNPX Monte Carlo code was utilized for the transport calculation of electrons, photons, and neutrons. Weight window variance-reduction techniques were introduced, and the dose equivalent outside the shield can be calculated with reasonably good statistics.

  3. The Structure and Function of Biological Networks

    ERIC Educational Resources Information Center

    Wu, Daniel Duanqing

    2010-01-01

    Biology has been revolutionized in recent years by an explosion in the availability of data. Transforming this new wealth of data into meaningful biological insights and clinical breakthroughs requires a complete overhaul both in the questions being asked and the methodologies used to answer them. A major challenge in organizing and understanding…

  4. Dynamics of biomolecules, ligand binding & biological functions

    NASA Astrophysics Data System (ADS)

    Yi, Myunggi

    Proteins are flexible and dynamic. One static structure alone does not often completely explain biological functions of the protein, and some proteins do not even have high resolution structures. In order to provide better understanding to the biological functions of nicotinic acetylcholine receptor, Diphtheria toxin repressor and M2 proton channel, the dynamics of these proteins are investigated using molecular modeling and molecular dynamics (MD) simulations. With absence of high resolution structure of alpha7 receptor, the homology models of apo and cobra toxin bound forms have been built. From the MD simulations of these model structures, we observed one subunit of apo simulation moved away from other four subunits. With local movement of flexible loop regions, the whole subunit tilted clockwise. These conformational changes occurred spontaneously, and were strongly correlated with the conformational change when the channel is activated by agonists. Unlike other computational studies, we directly compared our model of open conformation with the experimental data. However, the subunits of toxin bound form were stable, and conformational change is restricted by the bound cobra toxin. These results provide activation and inhibition mechanisms of alpha7 receptors and a possible explanation for intermediate conductance of the channel. Intramolecular complex of SH3-like domain with a proline-rich (Pr) peptide segment in Diphtheria toxin repressor (DtxR) is stabilized in inactive state. Upon activation of DtxR by transition metal binding, this intramolecular complex should be dissociated. The dynamics of this intramolecular complex is investigated using MD simulations and NMR spectroscopy. We observed spontaneous opening and closing motions of the Pr segment binding pockets in both Pr-SH3 and SH3 simulations. The MD simulation results and NMR relaxation data suggest that the Pr segment exhibits a binding ↔ unbinding equilibrium. Despite a wealth of experimental

  5. An interdisciplinary approach to study individuality in biological and physical systems functioning.

    PubMed

    Mygal, V P; But, A V; Mygal, G V; Klimenko, I A

    2016-01-01

    Signals of system functioning of different nature are presented in the parameter space (state-velocity-acceleration) as a trajectory of dynamic events. Such signals geometrization allows to reveal the hidden spatio-temporal correlation in dynamics of systems functioning. It is shown that the nature of relationship between the dynamic parameters of signal determines the natural cycle of sensor functioning. Its restructuring displays the inherited features of systems functioning in signature package. The universal differential-geometry parameters and new integrative indexes of system functioning are used to analyze the signatures of biological and physical signals. PMID:27412253

  6. An interdisciplinary approach to study individuality in biological and physical systems functioning

    PubMed Central

    Mygal, V. P.; But, A. V.; Mygal, G. V.; Klimenko, I. A.

    2016-01-01

    Signals of system functioning of different nature are presented in the parameter space (state-velocity-acceleration) as a trajectory of dynamic events. Such signals geometrization allows to reveal the hidden spatio-temporal correlation in dynamics of systems functioning. It is shown that the nature of relationship between the dynamic parameters of signal determines the natural cycle of sensor functioning. Its restructuring displays the inherited features of systems functioning in signature package. The universal differential-geometry parameters and new integrative indexes of system functioning are used to analyze the signatures of biological and physical signals. PMID:27412253

  7. An interdisciplinary approach to study individuality in biological and physical systems functioning

    NASA Astrophysics Data System (ADS)

    Mygal, V. P.; But, A. V.; Mygal, G. V.; Klimenko, I. A.

    2016-07-01

    Signals of system functioning of different nature are presented in the parameter space (state-velocity-acceleration) as a trajectory of dynamic events. Such signals geometrization allows to reveal the hidden spatio-temporal correlation in dynamics of systems functioning. It is shown that the nature of relationship between the dynamic parameters of signal determines the natural cycle of sensor functioning. Its restructuring displays the inherited features of systems functioning in signature package. The universal differential-geometry parameters and new integrative indexes of system functioning are used to analyze the signatures of biological and physical signals.

  8. Fusicoccanes: diterpenes with surprising biological functions.

    PubMed

    de Boer, Albertus H; de Vries-van Leeuwen, Ingrid J

    2012-06-01

    Fusicoccin is the best-studied member of a class of diterpenes sharing a 5-8-5 ring structure, called fusicoccanes. Fusicoccin was and still is a 'tool in plant physiology', targeting the main engine of plasma membrane transport, the P-type H(+)-ATPase, assisted by members of the 14-3-3 family. The key position of 14-3-3 proteins in cell biology, combined with a broader specificity of other fusicoccanes as shown by crystallography studies, make fusicoccanes a versatile tool in plant and animal biology. In this review, we examine recent evidence that fusicoccanes act on animal cells, describe the discovery of the fungal biosynthetic pathway and emphasize that lower (liverworts) and higher plants produce fusicoccanes with intriguing biological activities. PMID:22465041

  9. Anti-muscarinic adjunct therapy accelerates functional human oligodendrocyte repair.

    PubMed

    Abiraman, Kavitha; Pol, Suyog U; O'Bara, Melanie A; Chen, Guang-Di; Khaku, Zainab M; Wang, Jing; Thorn, David; Vedia, Bansi H; Ekwegbalu, Ezinne C; Li, Jun-Xu; Salvi, Richard J; Sim, Fraser J

    2015-02-25

    Therapeutic repair of myelin disorders may be limited by the relatively slow rate of human oligodendrocyte differentiation. To identify appropriate pharmacological targets with which to accelerate differentiation of human oligodendrocyte progenitors (hOPCs) directly, we used CD140a/O4-based FACS of human forebrain and microarray to hOPC-specific receptors. Among these, we identified CHRM3, a M3R muscarinic acetylcholine receptor, as being restricted to oligodendrocyte-biased CD140a(+)O4(+) cells. Muscarinic agonist treatment of hOPCs resulted in a specific and dose-dependent blockade of oligodendrocyte commitment. Conversely, when hOPCs were cocultured with human neurons, M3R antagonist treatment stimulated oligodendrocytic differentiation. Systemic treatment with solifenacin, an FDA-approved muscarinic receptor antagonist, increased oligodendrocyte differentiation of transplanted hOPCs in hypomyelinated shiverer/rag2 brain. Importantly, solifenacin treatment of engrafted animals reduced auditory brainstem response interpeak latency, indicative of increased conduction velocity and thereby enhanced functional repair. Therefore, solifenacin and other selective muscarinic antagonists represent new adjunct approaches to accelerate repair by engrafted human progenitors. PMID:25716865

  10. Function-Based Algorithms for Biological Sequences

    ERIC Educational Resources Information Center

    Mohanty, Pragyan Sheela P.

    2015-01-01

    Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

  11. Biological Structures, Interactions, Function and Behavior: Research Opportunities for Physicists

    NASA Astrophysics Data System (ADS)

    Concepcion, Gisela P.

    2008-06-01

    Studies on marine biomolecules at the Marine Natural Products Laboratory (MNPL) and studies on biomedically relevant proteins at the Virtual Laboratory of Biomolecular Structures (VIRLS) of the University of the Philippines Marine Science Institute (UPMSI) are presented. These serve to illustrate some underlying principles of biological structures, interactions, function and behavior, and also to draw out some unresolved questions in biology of possible interest to non-biologists. The Biological Structures course offered at UPMSI, which aims to introduce underlying biological principles to non-biology majors and to promote trans-disciplinary research efforts, is also presented.

  12. Functionalized apertures for the detection of chemical and biological materials

    DOEpatents

    Letant, Sonia E.; van Buuren, Anthony W.; Terminello, Louis J.; Thelen, Michael P.; Hope-Weeks, Louisa J.; Hart, Bradley R.

    2010-12-14

    Disclosed are nanometer to micron scale functionalized apertures constructed on a substrate made of glass, carbon, semiconductors or polymeric materials that allow for the real time detection of biological materials or chemical moieties. Many apertures can exist on one substrate allowing for the simultaneous detection of numerous chemical and biological molecules. One embodiment features a macrocyclic ring attached to cross-linkers, wherein the macrocyclic ring has a biological or chemical probe extending through the aperture. Another embodiment achieves functionalization by attaching chemical or biological anchors directly to the walls of the apertures via cross-linkers.

  13. Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

    PubMed Central

    Yun, Ye-Rang; Won, Jong Eun; Jeon, Eunyi; Lee, Sujin; Kang, Wonmo; Jo, Hyejin; Jang, Jun-Hyeog; Shin, Ueon Sang; Kim, Hae-Won

    2010-01-01

    Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues. PMID:21350642

  14. Accelerated Block Preconditioned Gradient method for large scale wave functions calculations in Density Functional Theory

    SciTech Connect

    Fattebert, J.-L.

    2010-01-20

    An Accelerated Block Preconditioned Gradient (ABPG) method is proposed to solve electronic structure problems in Density Functional Theory. This iterative algorithm is designed to solve directly the non-linear Kohn-Sham equations for accurate discretization schemes involving a large number of degrees of freedom. It makes use of an acceleration scheme similar to what is known as RMM-DIIS in the electronic structure community. The method is illustrated with examples of convergence for large scale applications using a finite difference discretization and multigrid preconditioning.

  15. BioFNet: biological functional network database for analysis and synthesis of biological systems.

    PubMed

    Kurata, Hiroyuki; Maeda, Kazuhiro; Onaka, Toshikazu; Takata, Takenori

    2014-09-01

    In synthetic biology and systems biology, a bottom-up approach can be used to construct a complex, modular, hierarchical structure of biological networks. To analyze or design such networks, it is critical to understand the relationship between network structure and function, the mechanism through which biological parts or biomolecules are assembled into building blocks or functional networks. A functional network is defined as a subnetwork of biomolecules that performs a particular function. Understanding the mechanism of building functional networks would help develop a methodology for analyzing the structure of large-scale networks and design a robust biological circuit to perform a target function. We propose a biological functional network database, named BioFNet, which can cover the whole cell at the level of molecular interactions. The BioFNet takes an advantage in implementing the simulation program for the mathematical models of the functional networks, visualizing the simulated results. It presents a sound basis for rational design of biochemical networks and for understanding how functional networks are assembled to create complex high-level functions, which would reveal design principles underlying molecular architectures. PMID:23894104

  16. Diazoxide accelerates wound healing by improving EPC function.

    PubMed

    Li, Zhang-Peng; Xin, Ru-Juan; Yang, Hong; Jiang, Guo-Jun; Deng, Ya-Ping; Li, Dong-Jie; Shen, Fu-Ming

    2016-01-01

    Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway. PMID:27100489

  17. [The biologic functional surfaces and their applications in tissue engineering].

    PubMed

    Yao, Fanglian; Chen, Man; Zhang, Hong; Zhang, Haiyue; An, Xiaoyan; Yao, Kangde

    2007-10-01

    The construction of biologic functional surfaces of materials, from the visual angle of material science, is aimed to make the biomaterials adapted by tissues, and to endow them with dynamic conformity; moreover, from the view-point of clinical applications, it is the functional surface to join the environmental tissues with the implanted material, playing the role of artificial extracellular matrix (ECM). The architecture of biologic functional surface is very important in tissue engineering science. Here the primary concepts of biological surface science and the construction and application of biofunctional surfaces in tissue engineering are reviewed. PMID:18027721

  18. Tunable ultrasensitivity: functional decoupling and biological insights.

    PubMed

    Wang, Guanyu; Zhang, Mengshi

    2016-01-01

    Sensitivity has become a basic concept in biology, but much less is known about its tuning, probably because allosteric cooperativity, the best known mechanism of sensitivity, is determined by rigid conformations of interacting molecules and is thus difficult to tune. Reversible covalent modification (RCM), owing to its systems-level ingenuity, can generate concentration based, tunable sensitivity. Using a mathematical model of regulated RCM, we find sensitivity tuning can be decomposed into two orthogonal modes, which provide great insights into vital biological processes such as tissue development and cell cycle progression. We find that decoupling of the two modes of sensitivity tuning is critical to fidelity of cell fate decision; the decoupling is thus important in development. The decomposition also allows us to solve the 'wasteful degradation conundrum' in budding yeast cell cycle checkpoint, which further leads to discovery of a subtle but essential difference between positive feedback and double negative feedback. The latter guarantees revocability of stress-induced cell cycle arrest; while the former does not. By studying concentration conditions in the system, we extend applicability of ultrasensitivity and explain the ubiquity of reversible covalent modification. PMID:26847155

  19. Tunable ultrasensitivity: functional decoupling and biological insights

    PubMed Central

    Wang, Guanyu; Zhang, Mengshi

    2016-01-01

    Sensitivity has become a basic concept in biology, but much less is known about its tuning, probably because allosteric cooperativity, the best known mechanism of sensitivity, is determined by rigid conformations of interacting molecules and is thus difficult to tune. Reversible covalent modification (RCM), owing to its systems-level ingenuity, can generate concentration based, tunable sensitivity. Using a mathematical model of regulated RCM, we find sensitivity tuning can be decomposed into two orthogonal modes, which provide great insights into vital biological processes such as tissue development and cell cycle progression. We find that decoupling of the two modes of sensitivity tuning is critical to fidelity of cell fate decision; the decoupling is thus important in development. The decomposition also allows us to solve the ‘wasteful degradation conundrum’ in budding yeast cell cycle checkpoint, which further leads to discovery of a subtle but essential difference between positive feedback and double negative feedback. The latter guarantees revocability of stress-induced cell cycle arrest; while the former does not. By studying concentration conditions in the system, we extend applicability of ultrasensitivity and explain the ubiquity of reversible covalent modification. PMID:26847155

  20. Biology under construction: in vitro reconstitution of cellular function

    PubMed Central

    Liu, Allen P.; Fletcher, Daniel A.

    2010-01-01

    We are much better at taking cells apart than putting them together. Reconstitution of biological processes from component molecules has been a powerful but difficult approach to studying functional organization in biology. Recently, the convergence of biochemical and cell biological advances with new experimental and computational tools is providing the opportunity to reconstitute increasingly complex processes. We predict that this bottom-up strategy will uncover basic processes that guide cellular assembly, advancing both basic and applied sciences. PMID:19672276

  1. Do US Black Women Experience Stress-Related Accelerated Biological Aging?

    PubMed Central

    Hicken, Margaret T.; Pearson, Jay A.; Seashols, Sarah J.; Brown, Kelly L.; Cruz, Tracey Dawson

    2010-01-01

    We hypothesize that black women experience accelerated biological aging in response to repeated or prolonged adaptation to subjective and objective stressors. Drawing on stress physiology and ethnographic, social science, and public health literature, we lay out the rationale for this hypothesis. We also perform a first population-based test of its plausibility, focusing on telomere length, a biomeasure of aging that may be shortened by stressors. Analyzing data from the Study of Women's Health Across the Nation (SWAN), we estimate that at ages 49–55, black women are 7.5 years biologically “older” than white women. Indicators of perceived stress and poverty account for 27% of this difference. Data limitations preclude assessing objective stressors and also result in imprecise estimates, limiting our ability to draw firm inferences. Further investigation of black-white differences in telomere length using large-population-based samples of broad age range and with detailed measures of environmental stressors is merited. PMID:20436780

  2. Printable Bioelectronics To Investigate Functional Biological Interfaces.

    PubMed

    Manoli, Kyriaki; Magliulo, Maria; Mulla, Mohammad Yusuf; Singh, Mandeep; Sabbatini, Luigia; Palazzo, Gerardo; Torsi, Luisa

    2015-10-19

    Thin-film transistors can be used as high-performance bioelectronic devices to accomplish tasks such as sensing or controlling the release of biological species as well as transducing the electrical activity of cells or even organs, such as the brain. Organic, graphene, or zinc oxide are used as convenient printable semiconducting layers and can lead to high-performance low-cost bioelectronic sensing devices that are potentially very useful for point-of-care applications. Among others, electrolyte-gated transistors are of interest as they can be operated as capacitance-modulated devices, because of the high capacitance of their charge double layers. Specifically, it is the capacitance of the biolayer, being lowest in a series of capacitors, which controls the output current of the device. Such an occurrence allows for extremely high sensitivity towards very weak interactions. All the aspects governing these processes are reviewed here. PMID:26420480

  3. Chemical Biology for Understanding Matrix Metalloproteinase Function

    PubMed Central

    Knapinska, Anna; Fields, Gregg B.

    2013-01-01

    The matrix metalloproteinase (MMP) family has long been associated with normal physiological processes such as embryonic implantation, tissue remodeling, organ development, and wound healing, as well as multiple aspects of cancer initiation and progression, osteoarthritis, inflammatory and vascular diseases, and neurodegenerative diseases. The development of chemically designed MMP probes has advanced our understanding of the roles of MMPs in disease in addition to shedding considerable light on the mechanisms of MMP action. The first generation of protease-activated agents has demonstrated proof of principle as well as providing impetus for in vivo applications. One common problem has been a lack of agent stability at nontargeted tissues and organs due to activation by multiple proteases. The present review considers how chemical biology has impacted the progress made in understanding the roles of MMPs in disease and the basic mechanisms of MMP action. PMID:22933318

  4. The evolutionary origin of biological function and complexity.

    PubMed

    Pross, Addy

    2013-04-01

    The identification of dynamic kinetic stability (DKS) as a stability kind that governs the evolutionary process for both chemical and biological replicators, opens up new avenues for uncovering the chemical basis of biological phenomena. In this paper, we utilize the DKS concept to explore the chemical roots of two of biology's central concepts--function and complexity. It is found that the selection rule in the world of persistent replicating systems--from DKS less stable to DKS more stable--is the operational law whose very existence leads to the creation of function from of a world initially devoid of function. The origin of biological complexity is found to be directly related to the origin of function through an underlying connection between the two phenomena. Thus the emergence of both function and complexity during abiogenesis, and their growing expression during biological evolution, are found to be governed by the same single driving force, the drive toward greater DKS. It is reaffirmed that the essence of biological phenomena can be best revealed by uncovering biology's chemical roots, by elucidating the physicochemical principles that governed the process by which life on earth emerged from inanimate matter. PMID:23512244

  5. Functional mapping in biology and medicine

    SciTech Connect

    McEachron, D.L.

    1986-01-01

    This book contains 10 selections. Some of the titles are: Two Views of Functional Mapping and Autoradiography; Quantitative Analysis of Autoradiographs; Hardware and Software Design Considerations in Engineering an Image Processing Workstation: Autoradiographic Analysis with DUMAS and the BRAIN Autoradiograph Analysis Software Package (with 1 color plate); and Quantitative Autoradiography and in vitro Radioligand Binding.

  6. Design and characterization of combined function multipole magnet for accelerators

    SciTech Connect

    Sinha, Gautam; Singh, Gurnam

    2008-12-15

    This paper presents the design and analysis of a multipurpose combined function magnet for use in accelerators. This magnet consists of three corrector magnets: (i) skew quadrupole, (ii) horizontal dipole, and (iii) vertical dipole magnets, along with the main sextupole magnet. The strength of the corrector magnets is smaller than that of the main sextupole magnet. The strength of all the four magnets can be varied independently. The excitation strength required to produce skew quadrupole gradient and the presence of various multipole components in the magnet are estimated using first order perturbation theory. The experimental data for the variation of the sextupole strength and its higher order multipoles in the presence of skew quadrupole excitations are presented and compared to the theoretical predictions. Simulation using two-dimensional fine element code, Poisson, is also done. Results obtained from all the above three methods are found to be in good agreement with each other. The variations of skew quadrupole gradient for different sextupole excitations are also measured. The validity of this theory is also checked for various combinations of excitations including the case where magnet gets saturated. The excitation strengths required for producing the horizontal and vertical dipole fields are estimated analytically along with the presence of various multipoles. Theoretical predictions of permissible multipoles are compared to the results obtained from simulation.

  7. Genomic Functionalization: The Next Revolution In Biology

    SciTech Connect

    Anderson, Peter; Schoeniger, Joseph S.; Imbro, Paula M.

    2014-07-01

    We have implemented a ligand-alignment algorithm into our developed computational pipeline for identifying specificity-determining features (SDFs) in protein-ligand complexes. Given a set of protein-ligand complex structures, the algorithm aligns the complexes by ligand rather than by the C -RMSD or standard approach, providing a single reference frame for extracting SDFs. We anticipate that this ligand-alignment capability will be highly useful for protein function prediction. We already have a database containing > 20 K ligand-protein complex crystal structures taken from the Protein Data Bank. By aligning these proteins to single reference frames using ligand alignment, we can submit the complexes to our pipeline for SDF extraction. The SDFs derived from this training procedure can be used as thumbprints that are hallmarks of individual enzyme classes. These SDF thumbprints may then serve as guides to the prediction of function of new unknown proteins.

  8. Subspace accelerated inexact Newton method for large scale wave functions calculations in Density Functional Theory

    SciTech Connect

    Fattebert, J

    2008-07-29

    We describe an iterative algorithm to solve electronic structure problems in Density Functional Theory. The approach is presented as a Subspace Accelerated Inexact Newton (SAIN) solver for the non-linear Kohn-Sham equations. It is related to a class of iterative algorithms known as RMM-DIIS in the electronic structure community. The method is illustrated with examples of real applications using a finite difference discretization and multigrid preconditioning.

  9. Biological assessments for the low energy demonstration accelerator, 1996 and 1997

    SciTech Connect

    Cross, S.

    1998-12-31

    The Department of Energy (DOE) plans to build, install, and operate a Low Energy Demonstration Accelerator (LMA) in Technical Area 53 of the Los Alamos National Laboratory (LANL). LEDA will demonstrate the accelerator technology necessary to produce tritium, but is not designed to produce tritium at LANL. USFWS reviewers of the Biological Assessment prepared for LEDA insisted that the main drainage be monitored to measure and document changes to vegetation, soils, wildlife, and habitats due to LEDA effluent discharges. The Biology Team of ESH-20 (LANL`s Ecology Group) has performed these monitoring activities during 1996 and 1997 to document baseline conditions before LEDA released significant effluent discharges. Quarterly monitoring of the outfall which will discharge LEDA blowdown effluent had one exceedance of permitted parameters, a high chlorine discharge that was quickly remedied. Samples from 12 soil pits in the drainage area contained no hydric indicators, such as organic matter in the upper layers, streaking, organic pans, and oxidized rhizospheres. Vegetation transacts in the meadows that LEDA discharges will flow through contained 44 species of herbaceous plants, all upland taxa. Surveys of resident birds, reptiles, and amphibians documented a fauna typical of local dry canyons. No threatened or endangered species inhabit the project area, but increased effluent releases may make the area more attractive to many wildlife species, an endangered raptor, and several other species of concern. Biological best management practices especially designed for LEDA are discussed, including protection of floodplains, erosion control measures, hazards posed by increased usage of the area by deer and elk and revegetation of disturbed areas.

  10. Autofluorescence: Biological functions and technical applications.

    PubMed

    García-Plazaola, José Ignacio; Fernández-Marín, Beatriz; Duke, Stephen O; Hernández, Antonio; López-Arbeloa, Fernando; Becerril, José María

    2015-07-01

    Chlorophylls are the most remarkable examples of fluorophores, and their fluorescence has been intensively studied as a non-invasive tool for assessment of photosynthesis. Many other fluorophores occur in plants, such as alkaloids, phenolic compounds and porphyrins. Fluorescence could be more than just a physicochemical curiosity in the plant kingdom, as several functional roles in biocommunication occur or have been proposed. Besides, fluorescence emitted by secondary metabolites can convert damaging blue and UV into wavelengths potentially useful for photosynthesis. Detection of the fluorescence of some secondary phytochemicals may be a cue for some pollinators and/or seed dispersal organisms. Independently of their functions, plant fluorophores provide researchers with a tool that allows the visualization of some metabolites in plants and cells, complementing and overcoming some of the limitations of the use of fluorescent proteins and dyes to probe plant physiology and biochemistry. Some fluorophores are influenced by environmental interactions, allowing fluorescence to be also used as a specific stress indicator. PMID:26025527

  11. Labeling and functionalizing amphipols for biological applications.

    PubMed

    Le Bon, Christel; Popot, Jean-Luc; Giusti, Fabrice

    2014-10-01

    Amphipols (APols) are short amphipathic polymers developed as an alternative to detergents for handling membrane proteins (MPs) in aqueous solution. MPs are, as a rule, much more stable following trapping with APols than they are in detergent solutions. The best-characterized APol to date, called A8-35, is a mixture of short-chain sodium polyacrylates randomly derivatized with octylamine and isopropylamine. Its solution properties have been studied in detail, and it has been used extensively for biochemical and biophysical studies of MPs. One of the attractive characteristics of APols is that it is relatively easy to label them, isotopically or otherwise, without affecting their physical-chemical properties. Furthermore, several variously modified APols can be mixed, achieving multiple functionalization of MP/APol complexes in the easiest possible manner. Labeled or tagged APols are being used to study the solution properties of APols, their miscibility, their biodistribution upon injection into living organisms, their association with MPs and the composition, structure and dynamics of MP/APol complexes, examining the exchange of surfactants at the surface of MPs, labeling MPs to follow their distribution in fractionation experiments or to immobilize them, increasing the contrast between APols and solvent or MPs in biophysical experiments, improving NMR spectra, etc. Labeling or functionalization of APols can take various courses, each of which has its specific constraints and advantages regarding both synthesis and purification. The present review offers an overview of the various derivatives of A8-35 and its congeners that have been developed in our laboratory and discusses the pros and cons of various synthetic routes. PMID:24696186

  12. Labeling and Functionalizing Amphipols for Biological Applications

    PubMed Central

    Bon, Christel Le; Popot, Jean-Luc; Giusti, Fabrice

    2014-01-01

    Amphipols (APols) are short amphipathic polymers developed as an alternative to detergents for handling membrane proteins (MPs) in aqueous solution. MPs are, as a rule, much more stable following trapping with APols than they are in detergent solutions. The best-characterized APol to date, called A8-35, is a mixture of short-chain sodium polyacrylates randomly derivatized with octylamine and isopropylamine. Its solution properties have been studied in detail, and it has been used extensively for biochemical and biophysical studies of MPs. One of the attractive characteristics of APols is that it is relatively easy to label them, isotopically or otherwise, without affecting their physical-chemical properties. Furthermore, several variously modified APols can be mixed, achieving multiple functionalization of MP/APol complexes in the easiest possible manner. Labeled or tagged APols are being used to study the solution properties of APols, their miscibility, their biodistribution upon injection into living organisms, their association with MPs and the composition, structure and dynamics of MP/APol complexes, examining the exchange of surfactants at the surface of MPs, labeling MPs to follow their distribution in fractionation experiments or to immobilize them, increasing the contrast between APols and solvent or MPs in biophysical experiments, improving NMR spectra, etc. Labeling or functionalization of APols can take various courses, each of which has its specific constraints and advantages regarding both synthesis and purification. The present review offers an overview of the various derivatives of A8-35 and its congeners that have been developed in our laboratory and discusses the pros and cons of various synthetic routes. PMID:24696186

  13. Connecting leptin signaling to biological function

    PubMed Central

    Allison, Margaret B.; Myers, Martin G.

    2014-01-01

    Hypothalamic leptin action promotes negative energy balance and modulates glucose homeostasis, as well as serving as a permissive signal to the neuroendocrine axes that control growth and reproduction. Since the initial discovery of leptin 20 years ago, we have learned a great deal about the molecular mechanisms of leptin action. An important aspect of this has been the dissection of the cellular mechanisms of leptin signaling, and how specific leptin signals influence physiology. Leptin acts via the long form of the leptin receptor, LepRb. LepRb activation and subsequent tyrosine phosphorylation recruits and activates multiple signaling pathways, including STAT transcription factors, SHP2 and ERK signaling, the IRS-protein/PI3Kinase pathway, and SH2B1. Each of these pathways controls specific aspects of leptin action and physiology. Important inhibitory pathways mediated by suppressor of cytokine signaling (SOCS) proteins and protein tyrosine phosphatases (PTPases) also limit physiologic leptin action. This review summarizes the signaling pathways engaged by LepRb and their effects on energy balance, glucose homeostasis, and reproduction. Particular emphasis is given to the multiple mouse models which have been used to elucidate these functions in vivo. PMID:25232147

  14. [Biological experiments in microgravity: equilibrium function].

    PubMed

    Gorgiladze, G I; Shipov, A A; Horn, E

    2012-01-01

    The review deals with the investigations of structural and functional modifications in the equilibrium organ (EO) in invertebrates (coelenterates, shells, crustaceans and insects) and vertebrates (fishes, amphibians, rats, primates) on different ontogenetic stages in the condition of microgravity and during readaptation to the Earth's gravity. Results of the investigations detail the adaptive strategy of terrestrial organism in the environment lacking the gravitational components that leads to the discrepancy of an inner model of the body-environment schema constructed by the central nervous system at 1 g and the novel reality. It is manifested by ataxic behavior and increased graviceptors' afferentation against efferent system inactivation. The new condition is defined as a sensibilization phase ensued by the eluding phase: behavior obeys the innate motion strategy, whereas graviceptors' afferentation decreases due to activation of the efferent system. Readaptation to 1 G takes several to 50 days and proceeds as a sequence of slow in motion behavior, ataxia and vestibular sensitization. Reactivity of the gravitosensory system to microgravity was found to be age-dependent. Gain in the EO inertial mass in microgravity and reduction with return to 1 g indicates gravity relevance to EO genesis. PMID:23402139

  15. Evidence for a Role of Executive Functions in Learning Biology

    ERIC Educational Resources Information Center

    Rhodes, Sinéad M.; Booth, Josephine N.; Campbell, Lorna Elise; Blythe, Richard A.; Wheate, Nial J.; Delibegovic, Mirela

    2014-01-01

    Research examining cognition and science learning has focused on working memory, but evidence implicates a broader set of executive functions. The current study examined executive functions and learning of biology in young adolescents. Fifty-six participants, aged 12-13?years, completed tasks of working memory (Spatial Working Memory), inhibition…

  16. Distinguishing between "function" and "effect" in genome biology.

    PubMed

    Doolittle, W Ford; Brunet, Tyler D P; Linquist, Stefan; Gregory, T Ryan

    2014-05-01

    Much confusion in genome biology results from conflation of possible meanings of the word "function." We suggest that, in this connection, attention should be paid to evolutionary biologists and philosophers who have previously dealt with this problem. We need only decide that although all genomic structures have effects, only some of them should be said to have functions. Although it will very often be difficult or impossible to establish function (strictly defined), it should not automatically be assumed. We enjoin genomicists in particular to pay greater attention to parsing biological effects. PMID:24814287

  17. Tip110: Physical properties, primary structure, and biological functions.

    PubMed

    Whitmill, Amanda; Timani, Khalid Amine; Liu, Ying; He, Johnny J

    2016-03-15

    HIV-1 Tat-interacting protein of 110kDa (Tip110), also referred to as squamous cell carcinoma antigen recognized by T cells 3 (Sart3), p110 or p110(nrb), was initially identified as a cDNA clone (KIAA0156) without annotated functions. Over the past twenty years, several functions have been attributed to this protein. The proposed biological functions include roles for Tip110 in pre-mRNA splicing, gene transcription, stem cell biology, and development. Dysregulation of Tip110 is also a contributing factor in the development of cancer and other human diseases. It is clear that our understanding of this protein is rapidly evolving. In this review, we aimed to provide a summary of all the existing literature on this gene/protein and its proposed biological functions. PMID:26896687

  18. Evolutionary cell biology: functional insight from "endless forms most beautiful".

    PubMed

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

    2015-12-15

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. PMID:26668171

  19. Industrialization of Biology. A Roadmap to Accelerate the Advanced Manufacturing of Chemicals

    SciTech Connect

    Friedman, Douglas C.

    2015-09-01

    The report stresses the need for efforts to inform the public of the nature of industrial biotechnology and of its societal benefits, and to make sure that concerns are communicated effectively between the public and other stakeholders. In addition to scientific advances, a number of governance and societal factors will influence the industrialization of biology. Industry norms and standards need to be established in areas such as read/write accuracy for DNA, data and machine technology specifications, and organism performance in terms of production rates and yields. An updated regulatory regime is also needed to accelerate the safe commercialization of new host organisms, metabolic pathways, and chemical products, and regulations should be coordinated across nations to enable rapid, safe, and global access to new technologies and products.

  20. Experimental stand for studying the impact of laser-accelerated protons on biological objects

    NASA Astrophysics Data System (ADS)

    Burdonov, K. F.; Eremeev, A. A.; Ignatova, N. I.; Osmanov, R. R.; Sladkov, A. D.; Soloviev, A. A.; Starodubtsev, M. V.; Ginzburg, V. N.; Kuz'min, A. A.; Maslennikova, A. V.; Revet, G.; Sergeev, A. M.; Fuchs, J.; Khazanov, E. A.; Chen, S.; Shaykin, A. A.; Shaikin, I. A.; Yakovlev, I. V.

    2016-04-01

    An original experimental stand is presented, aimed at studying the impact of high-energy protons, produced by the laser-plasma interaction at a petawatt power level, on biological objects. In the course of pilot experiments with the energy of laser-accelerated protons up to 25 MeV, the possibility is demonstrated of transferring doses up to 10 Gy to the object of study in a single shot with the magnetic separation of protons from parasitic X-ray radiation and fast electrons. The technique of irradiating the cell culture HeLa Kyoto and measuring the fraction of survived cells is developed. The ways of optimising the parameters of proton beams and the suitable methods of their separation with respect to energy and transporting to the studied living objects are discussed. The construction of the stand is intended for the improvement of laser technologies for hadron therapy of malignant neoplasms.

  1. Validity of Body-Worn Sensor Acceleration Metrics to Index Upper Extremity Function in Hemiparetic Stroke

    PubMed Central

    Urbin, M.A.; Bailey, Ryan R.; Lang, Catherine E.

    2015-01-01

    Background and Purpose In people with stroke, real-world use of the paretic upper extremity influences function. Therefore, measures of real-world use are of value for guiding rehabilitation. We undertook a study to identify the acceleration characteristics that have a stable association with upper extremity function and sensitivity to within-participant fluctuations in function over multiple sessions of task-specific training. Methods Twenty-seven adults > 6 months post stroke with upper extremity paresis participated. Signals from wrist-worn accelerometers were sampled at 30 Hz during seven sessions of task-specific training. Paretic upper extremity function was evaluated with the Action Research Arm Test (ARAT). We used Spearman correlations to examine within-session associations between acceleration metrics and ARAT performance. A mixed model was used to determine which metrics were sensitive to within-participant fluctuations in upper extremity function across the seven training sessions. Results Upper extremity function correlated with bilateral acceleration variability and use ratio during five and six session, respectively. Time accelerating between 76-100% of peak acceleration correlated with function in six sessions. Variability of the paretic upper extremity acceleration and the ratio of acceleration variability between upper extremities were associated with function during all seven sessions. Variability in both the acceleration of the paretic upper extremity, and acceleration of the paretic and non-paretic extremities combined were sensitive to within-participant fluctuations in function across training sessions. Conclusion Multiple features of the acceleration profile track with upper extremity function within and across sessions of task-specific training. It may be possible to monitor these features with accelerometers to index upper extremity function outside of clinical settings. PMID:25742378

  2. Accelerating Smith-Waterman Algorithm for Biological Database Search on CUDA-Compatible GPUs

    NASA Astrophysics Data System (ADS)

    Munekawa, Yuma; Ino, Fumihiko; Hagihara, Kenichi

    This paper presents a fast method capable of accelerating the Smith-Waterman algorithm for biological database search on a cluster of graphics processing units (GPUs). Our method is implemented using compute unified device architecture (CUDA), which is available on the nVIDIA GPU. As compared with previous methods, our method has four major contributions. (1) The method efficiently uses on-chip shared memory to reduce the data amount being transferred between off-chip video memory and processing elements in the GPU. (2) It also reduces the number of data fetches by applying a data reuse technique to query and database sequences. (3) A pipelined method is also implemented to overlap GPU execution with database access. (4) Finally, a master/worker paradigm is employed to accelerate hundreds of database searches on a cluster system. In experiments, the peak performance on a GeForce GTX 280 card reaches 8.32 giga cell updates per second (GCUPS). We also find that our method reduces the amount of data fetches to 1/140, achieving approximately three times higher performance than a previous CUDA-based method. Our 32-node cluster version is approximately 28 times faster than a single GPU version. Furthermore, the effective performance reaches 75.6 giga instructions per second (GIPS) using 32 GeForce 8800 GTX cards.

  3. Infrared Structural Biology: Detect Functionally Important Structural Motions of Proteins

    NASA Astrophysics Data System (ADS)

    Xie, Aihua

    Proteins are dynamic. Lack of dynamic structures of proteins hampers our understanding of protein functions. Infrared structural biology (IRSB) is an emerging technology. There are several advantages of IRSB for mechanistic studies of proteins: (1) its excellent dynamic range (detecting structural motions from picoseconds to >= seconds); (2) its high structural sensitivity (detect tiny but functionally important structural motions such as proton transfer and changes in hydrogen bonding interaction); (3) its ability to detect different structural motions simultaneously. Successful development of infrared structural biology demands not only new experimental techniques (from infrared technologies to chemical synthesis and cell biology), but also new data processing (how to translate infrared signals into quantitative structural information of proteins). These topics will be discussed as well as examples of how to use IRSB to study structure-function relationship of proteins. This work was supported by NSF DBI1338097 and OCAST HR10-078.

  4. Can Simple Biophysical Principles Yield Complicated Biological Functions?

    NASA Astrophysics Data System (ADS)

    Liphardt, Jan

    2011-03-01

    About once a year, a new regulatory paradigm is discovered in cell biology. As of last count, eukaryotic cells have more than 40 distinct ways of regulating protein concentration and function. Regulatory possibilities include site-specific phosphorylation, epigenetics, alternative splicing, mRNA (re)localization, and modulation of nucleo-cytoplasmic transport. This raises a simple question. Do all the remarkable things cells do, require an intricately choreographed supporting cast of hundreds of molecular machines and associated signaling networks? Alternatively, are there a few simple biophysical principles that can generate apparently very complicated cellular behaviors and functions? I'll discuss two problems, spatial organization of the bacterial chemotaxis system and nucleo-cytoplasmic transport, where the latter might be true. In both cases, the ability to precisely quantify biological organization and function, at the single-molecule level, helped to find signatures of basic biological organizing principles.

  5. Systematic Functional Annotation and Visualization of Biological Networks.

    PubMed

    Baryshnikova, Anastasia

    2016-06-22

    Large-scale biological networks represent relationships between genes, but our understanding of how networks are functionally organized is limited. Here, I describe spatial analysis of functional enrichment (SAFE), a systematic method for annotating biological networks and examining their functional organization. SAFE visualizes the network in 2D space and measures the continuous distribution of functional enrichment across local neighborhoods, producing a list of the associated functions and a map of their relative positioning. I applied SAFE to annotate the Saccharomyces cerevisiae genetic interaction similarity network and protein-protein interaction network with gene ontology terms. SAFE annotations of the genetic network matched manually derived annotations, while taking less than 1% of the time, and proved robust to noise and sensitive to biological signal. Integration of genetic interaction and chemical genomics data using SAFE revealed a link between vesicle-mediate transport and resistance to the anti-cancer drug bortezomib. These results demonstrate the utility of SAFE for examining biological networks and understanding their functional organization. PMID:27237738

  6. Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

    NASA Technical Reports Server (NTRS)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

  7. Measurement of Beryllium in Biological Samples by Accelerator Mass Spectrometry: Applications for Studying Chronic Beryllium Disease

    SciTech Connect

    Chiarappa-Zucca, M L; Finkel, R C; Martinelli, R E; McAninch, J E; Nelson, D O; Turtletaub, K W

    2004-04-15

    A method using accelerator mass spectrometry (AMS) has been developed for quantifying attomoles of beryllium (Be) in biological samples. This method provides the sensitivity to trace Be in biological samples at very low doses with the purpose of identifying the molecular targets involved in chronic beryllium disease. Proof of the method was tested by administering 0.001, 0.05, 0.5 and 5.0 {micro}g {sup 9}Be and {sup 10}Be by intraperitoneal injection to male mice and removing spleen, liver, femurs, blood, lung, and kidneys after 24 h exposure. These samples were prepared for AMS analysis by tissue digestion in nitric acid, followed by further organic oxidation with hydrogen peroxide and ammonium persulfate and lastly, precipitation of Be with ammonium hydroxide, and conversion to beryllium oxide at 800 C. The {sup 10}Be/{sup 9}Be ratio of the extracted beryllium oxide was measured by AMS and Be in the original sample was calculated. Results indicate that Be levels were dose-dependent in all tissues and the highest levels were measured in the spleen and liver. The measured {sup 10}Be/{sup 9}Be ratios spanned 4 orders of magnitude, from 10{sup -10} to 10{sup -14}, with a detection limit of 3.0 x 10{sup -14}, which is equivalent to 0.8 attomoles of {sup 10}Be. These results show that routine quantification of nanogram levels of Be in tissues is possible and that AMS is a sensitive method that can be used in biological studies to understand the molecular dosimetry of Be and mechanisms of toxicity.

  8. Linking structural features of protein complexes and biological function.

    PubMed

    Sowmya, Gopichandran; Breen, Edmond J; Ranganathan, Shoba

    2015-09-01

    Protein-protein interaction (PPI) establishes the central basis for complex cellular networks in a biological cell. Association of proteins with other proteins occurs at varying affinities, yet with a high degree of specificity. PPIs lead to diverse functionality such as catalysis, regulation, signaling, immunity, and inhibition, playing a crucial role in functional genomics. The molecular principle of such interactions is often elusive in nature. Therefore, a comprehensive analysis of known protein complexes from the Protein Data Bank (PDB) is essential for the characterization of structural interface features to determine structure-function relationship. Thus, we analyzed a nonredundant dataset of 278 heterodimer protein complexes, categorized into major functional classes, for distinguishing features. Interestingly, our analysis has identified five key features (interface area, interface polar residue abundance, hydrogen bonds, solvation free energy gain from interface formation, and binding energy) that are discriminatory among the functional classes using Kruskal-Wallis rank sum test. Significant correlations between these PPI interface features amongst functional categories are also documented. Salt bridges correlate with interface area in regulator-inhibitors (r = 0.75). These representative features have implications for the prediction of potential function of novel protein complexes. The results provide molecular insights for better understanding of PPIs and their relation to biological functions. PMID:26131659

  9. Applications of large-scale density functional theory in biology

    NASA Astrophysics Data System (ADS)

    Cole, Daniel J.; Hine, Nicholas D. M.

    2016-10-01

    Density functional theory (DFT) has become a routine tool for the computation of electronic structure in the physics, materials and chemistry fields. Yet the application of traditional DFT to problems in the biological sciences is hindered, to a large extent, by the unfavourable scaling of the computational effort with system size. Here, we review some of the major software and functionality advances that enable insightful electronic structure calculations to be performed on systems comprising many thousands of atoms. We describe some of the early applications of large-scale DFT to the computation of the electronic properties and structure of biomolecules, as well as to paradigmatic problems in enzymology, metalloproteins, photosynthesis and computer-aided drug design. With this review, we hope to demonstrate that first principles modelling of biological structure-function relationships are approaching a reality.

  10. Applications of large-scale density functional theory in biology.

    PubMed

    Cole, Daniel J; Hine, Nicholas D M

    2016-10-01

    Density functional theory (DFT) has become a routine tool for the computation of electronic structure in the physics, materials and chemistry fields. Yet the application of traditional DFT to problems in the biological sciences is hindered, to a large extent, by the unfavourable scaling of the computational effort with system size. Here, we review some of the major software and functionality advances that enable insightful electronic structure calculations to be performed on systems comprising many thousands of atoms. We describe some of the early applications of large-scale DFT to the computation of the electronic properties and structure of biomolecules, as well as to paradigmatic problems in enzymology, metalloproteins, photosynthesis and computer-aided drug design. With this review, we hope to demonstrate that first principles modelling of biological structure-function relationships are approaching a reality. PMID:27494095

  11. Modeling Functional Motions of Biological Systems by Customized Natural Moves.

    PubMed

    Demharter, Samuel; Knapp, Bernhard; Deane, Charlotte M; Minary, Peter

    2016-08-23

    Simulating the functional motions of biomolecular systems requires large computational resources. We introduce a computationally inexpensive protocol for the systematic testing of hypotheses regarding the dynamic behavior of proteins and nucleic acids. The protocol is based on natural move Monte Carlo, a highly efficient conformational sampling method with built-in customization capabilities that allows researchers to design and perform a large number of simulations to investigate functional motions in biological systems. We demonstrate the use of this protocol on both a protein and a DNA case study. Firstly, we investigate the plasticity of a class II major histocompatibility complex in the absence of a bound peptide. Secondly, we study the effects of the epigenetic mark 5-hydroxymethyl on cytosine on the structure of the Dickerson-Drew dodecamer. We show how our customized natural moves protocol can be used to investigate causal relationships of functional motions in biological systems. PMID:27558715

  12. Venom Proteins from Parasitoid Wasps and Their Biological Functions

    PubMed Central

    Moreau, Sébastien J. M.; Asgari, Sassan

    2015-01-01

    Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies. PMID:26131769

  13. FETAL DEXAMETHASONE EXPOSURE ACCELERATES DEVELOPMENT OF RENAL FUNCTION: RELATIONSHIP TO DOSE, CELL DIFFERENTIATION AND GROWTH INHIBITION

    EPA Science Inventory

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. evertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. he current study examine...

  14. Microwave-accelerated bioassay technique for rapid and quantitative detection of biological and environmental samples.

    PubMed

    Mohammed, Muzaffer; Syed, Maleeha F; Aslan, Kadir

    2016-01-15

    Quantitative detection of molecules of interest from biological and environmental samples in a rapid manner, particularly with a relevant concentration range, is imperative to the timely assessment of human diseases and environmental issues. In this work, we employed the microwave-accelerated bioassay (MAB) technique, which is based on the combined use of circular bioassay platforms and microwave heating, for rapid and quantitative detection of Glial Fibrillary Acidic Protein (GFAP) and Shiga like toxin (STX 1). The proof-of-principle use of the MAB technique with the circular bioassay platforms for the rapid detection of GFAP in buffer based on colorimetric and fluorescence readouts was demonstrated with a 900W kitchen microwave. We also employed the MAB technique with a new microwave system (called the iCrystal system) for the detection of GFAP from mice with brain injuries and STX 1 from a city water stream. Control bioassays included the commercially available gold standard bioassay kits run at room temperature. Our results show that the lower limit of detection (LLOD) of the colorimetric and fluorescence based bioassays for GFAP was decreased by ~1000 times using the MAB technique and our circular bioassay platforms as compared to the commercially available bioassay kits. The overall bioassay time for GFAP and STX 1 was reduced from 4h using commercially available bioassay kits to 10min using the MAB technique. PMID:26356762

  15. Watering, fertilization, and slurry inoculation promote recovery of biological crust function in degraded soils.

    PubMed

    Maestre, Fernando T; Martín, Noelia; Díez, Beatriz; López-Poma, Rosario; Santos, Fernando; Luque, Ignacio; Cortina, Jordi

    2006-10-01

    Biological soil crusts are very sensitive to human-induced disturbances and are in a degraded state in many areas throughout their range. Given their importance in the functioning of arid and semiarid ecosystems, restoring these crusts may contribute to the recovery of ecosystem functionality in degraded areas. We conducted a factorial microcosm experiment to evaluate the effects of inoculation type (discrete fragments vs slurry), fertilization (control vs addition of composted sewage sludge), and watering frequency (two vs five times per week) on the cyanobacterial composition, nitrogen fixation, chlorophyll content, and net CO2 exchange rate of biological soil crusts inoculated on a semiarid degraded soil from SE Spain. Six months after the inoculation, the highest rates of nitrogen fixation and chlorophyll a content were found when the biological crusts were inoculated as slurry, composted sewage sludge was added, and the microcosms were watered five times per week. Net CO2 exchange rate increased when biological crusts were inoculated as slurry and the microcosms were watered five times per week. Denaturing gradient gel electrophoresis fingerprints and phylogenetic analyses indicated that most of the cyanobacterial species already present in the inoculated crust had the capability to spread and colonize the surface of the surrounding soil. These analyses showed that cyanobacterial communities were less diverse when the microcosms were watered five times per week, and that watering frequency (followed in importance by the addition of composted sewage sludge and inoculation type) was the treatment that most strongly influenced their composition. Our results suggest that the inoculation of biological soil crusts in the form of slurry combined with the addition of composted sewage sludge could be a suitable technique to accelerate the recovery of the composition and functioning of biological soil crusts in drylands. PMID:16710791

  16. Functional Agents to Biologically Control Deoxynivalenol Contamination in Cereal Grains

    PubMed Central

    Tian, Ye; Tan, Yanglan; Liu, Na; Liao, Yucai; Sun, Changpo; Wang, Shuangxia; Wu, Aibo

    2016-01-01

    Mycotoxins, as microbial secondary metabolites, frequently contaminate cereal grains and pose a serious threat to human and animal health around the globe. Deoxynivalenol (DON), a commonly detected Fusarium mycotoxin, has drawn utmost attention due to high exposure levels and contamination frequency in the food chain. Biological control is emerging as a promising technology for the management of DON contamination. Functional biological control agents (BCAs), which include antagonistic microbes, natural fungicides derived from plants and detoxification enzymes, can be used to control DON contamination at different stages of grain production. In this review, studies regarding different biological agents for DON control in recent years are summarized for the first time. Furthermore, this article highlights the significance of BCAs for controlling DON contamination, as well as the need for more practical and efficient BCAs concerning food safety. PMID:27064760

  17. Morpho-chemistry and functionality of diseased biological tissues

    NASA Astrophysics Data System (ADS)

    Lange, Marta; Cicchi, Riccardo; Pavone, Francesco

    2014-09-01

    Heart and cardiovascular diseases are one of the most common in the world, in particular - arthrosclerosis. The aim of the research is to distinguish pathological and healthy tissue regions in biological samples, in this case - to distinguish collagen and lipid rich regions within the arterial wall. In the work a specific combination of such methods are used: FLIM and SHG in order to evaluate the biological tissue morphology and functionality, so that this research could give a contribution for creating a new biological tissue imaging standard in the closest future. During the study the most appropriate parameter for fluorescence lifetime decay was chosen in order to evaluate lifetime decay parameters and the isotropy of the arterial wall and deposition, using statistical methods FFT and GLCM. The research gives a contribution or the future investigations for evaluating lipid properties when it can de-attach from the arterial wall and cause clotting in the blood vessel or even a stroke.

  18. From Structure and Function of Proteins Toward in Silico Biology

    NASA Astrophysics Data System (ADS)

    Yamato, Ichiro

    2013-01-01

    Researches of biology are targeted on three major flows, materials (or chemicals), energy, and information. I have been mainly concerned with the studies on bioenergy transducing mechanisms. I have studied the mechanism of secondary active transport systems and proposed an affinity change mechanism as a general hypothesis, then tried to confirm that it is applicable to other kinds of bioenergy transducing systems. Choosing Na+-translocating V-type ATPase from Enterococcus hirae as target, I hypothesized the affinity change mechanism for the energy transduction of this ATPase. Here I describe several three dimensional structures of parts of the ATPase supporting my hypothesis. From such detailed and extensive researches on protein structure/function relationship, we can proceed toward the in silico biology, which I described previously in 2007 ([1] "Toward in silico biology").

  19. Carbon-Oxygen Hydrogen Bonding in Biological Structure and Function

    PubMed Central

    Horowitz, Scott; Trievel, Raymond C.

    2012-01-01

    Carbon-oxygen (CH···O) hydrogen bonding represents an unusual category of molecular interactions first documented in biological structures over 4 decades ago. Although CH···O hydrogen bonding has remained generally underappreciated in the biochemical literature, studies over the last 15 years have begun to yield direct evidence of these interactions in biological systems. In this minireview, we provide a historical context of biological CH···O hydrogen bonding and summarize some major advancements from experimental studies over the past several years that have elucidated the importance, prevalence, and functions of these interactions. In particular, we examine the impact of CH···O bonds on protein and nucleic acid structure, molecular recognition, and enzyme catalysis and conclude by exploring overarching themes and unresolved questions regarding unconventional interactions in biomolecular structure. PMID:23048026

  20. Constructing biological pathway models with hybrid functional Petri nets.

    PubMed

    Doi, Atsushi; Fujita, Sachie; Matsuno, Hiroshi; Nagasaki, Masao; Miyano, Satoru

    2004-01-01

    In many research projects on modeling and analyzing biological pathways, the Petri net has been recognized as a promising method for representing biological pathways. From the pioneering works by Reddy et al., 1993, and Hofestädt, 1994, that model metabolic pathways by traditional Petri net, several enhanced Petri nets such as colored Petri net, stochastic Petri net, and hybrid Petri net have been used for modeling biological phenomena. Recently, Matsuno et al., 2003b, introduced the hybrid functional Petri net (HFPN) in order to give a more intuitive and natural modeling method for biological pathways than these existing Petri nets. Although the paper demonstrates the effectiveness of HFPN with two examples of gene regulation mechanism for circadian rhythms and apoptosis signaling pathway, there has been no detailed explanation about the method of HFPN construction for these examples. The purpose of this paper is to describe method to construct biological pathways with the HFPN step-by-step. The method is demonstrated by the well-known glycolytic pathway controlled by the lac operon gene regulatory mechanism. PMID:15724280

  1. Accelerating Wave Function Convergence in Interactive Quantum Chemical Reactivity Studies.

    PubMed

    Mühlbach, Adrian H; Vaucher, Alain C; Reiher, Markus

    2016-03-01

    The inherently high computational cost of iterative self-consistent field (SCF) methods proves to be a critical issue delaying visual and haptic feedback in real-time quantum chemistry. In this work, we introduce two schemes for SCF acceleration. They provide a guess for the initial density matrix of the SCF procedure generated by extrapolation techniques. SCF optimizations then converge in fewer iterations, which decreases the execution time of the SCF optimization procedure. To benchmark the proposed propagation schemes, we developed a test bed for performing quantum chemical calculations on sequences of molecular structures mimicking real-time quantum chemical explorations. Explorations of a set of six model reactions employing the semi-empirical methods PM6 and DFTB3 in this testing environment showed that the proposed propagation schemes achieved speedups of up to 30% as a consequence of a reduced number of SCF iterations. PMID:26788887

  2. Biological activity, membrane-targeting modification, and crystallization of soluble human decay accelerating factor expressed in E. coli

    PubMed Central

    White, Jennifer; Lukacik, Petra; Esser, Dirk; Steward, Michael; Giddings, Naomi; Bright, Jeremy R.; Fritchley, Sarah J.; Morgan, B. Paul; Lea, Susan M.; Smith, Geoffrey P.; Smith, Richard A.G.

    2004-01-01

    Decay-accelerating factor (DAF, CD55) is a glycophosphatidyl inositol-anchored glycoprotein that regulates the activity of C3 and C5 convertases. In addition to understanding the mechanism of complement inhibition by DAF through structural studies, there is also an interest in the possible therapeutic potential of the molecule. In this report we describe the cloning, expression in Escherichia coli, isolation and membrane-targeting modification of the four short consensus repeat domains of soluble human DAF with an additional C-terminal cysteine residue to permit site-specific modification. The purified refolded recombinant protein was active against both classical and alternative pathway assays of complement activation and had similar biological activity to soluble human DAF expressed in Pichia pastoris. Modification with a membrane-localizing peptide restored cell binding and gave a large increase in antihemolytic potency. These data suggested that the recombinant DAF was correctly folded and suitable for structural studies as well as being the basis for a DAF-derived therapeutic. Crystals of the E. coli-derived protein were obtained and diffracted to 2.2 Å, thus permitting the first detailed X-ray crystallography studies on a functionally active human complement regulator protein with direct therapeutic potential. PMID:15322283

  3. SU-E-T-54: Benefits of Biological Cost Functions

    SciTech Connect

    Demirag, N

    2014-06-01

    Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 and 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.

  4. Biological framework for soil aggregation: Implications for ecological functions.

    NASA Astrophysics Data System (ADS)

    Ghezzehei, Teamrat; Or, Dani

    2016-04-01

    Soil aggregation is heuristically understood as agglomeration of primary particles bound together by biotic and abiotic cementing agents. The organization of aggregates is believed to be hierarchical in nature; whereby primary particles bond together to form secondary particles and subsequently merge to form larger aggregates. Soil aggregates are not permanent structures, they continuously change in response to internal and external forces and other drivers, including moisture, capillary pressure, temperature, biological activity, and human disturbances. Soil aggregation processes and the resulting functionality span multiple spatial and temporal scales. The intertwined biological and physical nature of soil aggregation, and the time scales involved precluded a universally applicable and quantifiable framework for characterizing the nature and function of soil aggregation. We introduce a biophysical framework of soil aggregation that considers the various modes and factors of the genesis, maturation and degradation of soil aggregates including wetting/drying cycles, soil mechanical processes, biological activity and the nature of primary soil particles. The framework attempts to disentangle mechanical (compaction and soil fragmentation) from in-situ biophysical aggregation and provides a consistent description of aggregate size, hierarchical organization, and life time. It also enables quantitative description of biotic and abiotic functions of soil aggregates including diffusion and storage of mass and energy as well as role of aggregates as hot spots of nutrient accumulation, biodiversity, and biogeochemical cycles.

  5. Research advances on structure and biological functions of integrins.

    PubMed

    Pan, Li; Zhao, Yuan; Yuan, Zhijie; Qin, Guixin

    2016-01-01

    Integrins are an important family of adhesion molecules that were first discovered two decades ago. Integrins are transmembrane heterodimeric glycoprotein receptors consisting of α and β subunits, and are comprised of an extracellular domain, a transmembrane domain, and a cytoplasmic tail. Therein, integrin cytoplasmic domains may associate directly with numerous cytoskeletal proteins and intracellular signaling molecules, which are crucial for modulating fundamental cell processes and functions including cell adhesion, proliferation, migration, and survival. The purpose of this review is to describe the unique structure of each integrin subunit, primary cytoplasmic association proteins, and transduction signaling pathway of integrins, with an emphasis on their biological functions. PMID:27468395

  6. Deducing protein function by forensic integrative cell biology.

    PubMed

    Earnshaw, William C

    2013-12-01

    Our ability to sequence genomes has provided us with near-complete lists of the proteins that compose cells, tissues, and organisms, but this is only the beginning of the process to discover the functions of cellular components. In the future, it's going to be crucial to develop computational analyses that can predict the biological functions of uncharacterised proteins. At the same time, we must not forget those fundamental experimental skills needed to confirm the predictions or send the analysts back to the drawing board to devise new ones. PMID:24358025

  7. 5-methylcytosine in RNA: detection, enzymatic formation and biological functions

    PubMed Central

    Motorin, Yuri; Lyko, Frank; Helm, Mark

    2010-01-01

    The nucleobase modification 5-methylcytosine (m5C) is widespread both in DNA and different cellular RNAs. The functions and enzymatic mechanisms of DNA m5C-methylation were extensively studied during the last decades. However, the location, the mechanism of formation and the cellular function(s) of the same modified nucleobase in RNA still remain to be elucidated. The recent development of a bisulfite sequencing approach for efficient m5C localization in various RNA molecules puts ribo-m5C in a highly privileged position as one of the few RNA modifications whose detection is amenable to PCR-based amplification and sequencing methods. Additional progress in the field also includes the characterization of several specific RNA methyltransferase enzymes in various organisms, and the discovery of a new and unexpected link between DNA and RNA m5C-methylation. Numerous putative RNA:m5C-MTases have now been identified and are awaiting characterization, including the identification of their RNA substrates and their related cellular functions. In order to bring these recent exciting developments into perspective, this review provides an ordered overview of the detection methods for RNA methylation, of the biochemistry, enzymology and molecular biology of the corresponding modification enzymes, and discusses perspectives for the emerging biological functions of these enzymes. PMID:20007150

  8. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  9. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists

    PubMed Central

    Huang, Da Wei; Sherman, Brad T; Tan, Qina; Collins, Jack R; Alvord, W Gregory; Roayaei, Jean; Stephens, Robert; Baseler, Michael W; Lane, H Clifford; Lempicki, Richard A

    2007-01-01

    The DAVID Gene Functional Classification Tool uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context. PMID:17784955

  10. Systems analysis of biological networks in skeletal muscle function.

    PubMed

    Smith, Lucas R; Meyer, Gretchen; Lieber, Richard L

    2013-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation-contraction coupling enabling Ca(2+) release. Ca(2+) then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. PMID:23188744

  11. Mnk kinase pathway: Cellular functions and biological outcomes.

    PubMed

    Joshi, Sonali; Platanias, Leonidas C

    2014-08-26

    The mitogen-activated protein kinase (MAPK) interacting protein kinases 1 and 2 (Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation. In addition to the MAPKs (p38 or Erk), multiple studies suggest that the Mnk kinases can be regulated by other known kinases such as Pak2 and/or other unidentified kinases by phosphorylation of residues distinct from the sites phosphorylated by the MAPKs. Several studies have established multiple Mnk protein targets, including PSF, heterogenous nuclear ribonucleoprotein A1, Sprouty 2 and have lead to the identification of distinct biological functions and substrate specificity for the Mnk kinases. In this review we discuss the pathways regulating the Mnk kinases, their known substrates as well as the functional consequences of engagement of pathways controlled by Mnk kinases. These kinases play an important role in mRNA translation via their regulation of eukaryotic initiation factor 4E (eIF4E) and their functions have important implications in tumor biology as well as the regulation of drug resistance to anti-oncogenic therapies. Other studies have identified a role for the Mnk kinases in cap-independent mRNA translation, suggesting that the Mnk kinases can exert important functional effects independently of the phosphorylation of eIF4E. The role of Mnk kinases in inflammation and inflammation-induced malignancies is also discussed. PMID:25225600

  12. Biological properties of extracellular vesicles and their physiological functions.

    PubMed

    Yáñez-Mó, María; Siljander, Pia R-M; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E; Buzas, Edit I; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Cordeiro-da Silva, Anabela; Fais, Stefano; Falcon-Perez, Juan M; Ghobrial, Irene M; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H H; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Nolte-'t Hoen, Esther N M; Nyman, Tuula A; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; Del Portillo, Hernando A; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G; Vasconcelos, M Helena; Wauben, Marca H M; De Wever, Olivier

    2015-01-01

    In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

  13. Systems analysis of biological networks in skeletal muscle function

    PubMed Central

    Smith, Lucas R.; Meyer, Gretchen; Lieber, Richard L.

    2014-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation–contraction coupling enabling Ca2+ release. Ca2+ then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. PMID:23188744

  14. Biological properties of extracellular vesicles and their physiological functions

    PubMed Central

    Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier

    2015-01-01

    In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

  15. Probing the Xenopus laevis inner ear transcriptome for biological function

    PubMed Central

    2012-01-01

    Background The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis. Results Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip® Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization. Conclusions We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the

  16. High-resolution network biology: connecting sequence with function

    PubMed Central

    Ryan, Colm J.; Cimermančič, Peter; Szpiech, Zachary A.; Sali, Andrej; Hernandez, Ryan D.; Krogan, Nevan J.

    2014-01-01

    Proteins are not monolithic entities; rather, they can contain multiple domains that mediate distinct interactions, and their functionality can be regulated through post-translational modifications at multiple distinct sites. Traditionally, network biology has ignored such properties of proteins and has instead examined either the physical interactions of whole proteins or the consequences of removing entire genes. In this Review, we discuss experimental and computational methods to increase the resolution of protein– protein, genetic and drug–gene interaction studies to the domain and residue levels. Such work will be crucial for using interaction networks to connect sequence and structural information, and to understand the biological consequences of disease-associated mutations, which will hopefully lead to more effective therapeutic strategies. PMID:24197012

  17. Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

    PubMed

    Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica; Buch-Månson, Nina; Bovet, Nicolas; Nygård, Jesper; Martinez, Karen L; Meldal, Morten

    2016-01-11

    Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. PMID:26601641

  18. ACCELERATORS: A GUI tool for beta function measurement using MATLAB

    NASA Astrophysics Data System (ADS)

    Chen, Guang-Ling; Tian, Shun-Qiang; Jiang, Bo-Cheng; Liu, Gui-Min

    2009-04-01

    The beta function measurement is used to detect the shift in the betatron tune as the strength of an individual quadrupole magnet is varied. A GUI (graphic user interface) tool for the beta function measurement is developed using the MATLAB program language in the Linux environment, which facilitates the commissioning of the Shanghai Synchrotron Radiation Facility (SSRF) storage ring. In this paper, we describe the design of the application and give some measuring results and discussions about the definition of the measurement. The program has been optimized to solve some restrictions of the AT tracking code. After the correction with LOCO (linear optics from closed orbits), the horizontal and the vertical root mean square values (rms values) can be reduced to 0.12 and 0.10.

  19. Considerations to improve functional annotations in biological databases.

    PubMed

    Benítez-Páez, Alfonso

    2009-12-01

    Despite the great effort to design efficient systems allowing the electronic indexation of information concerning genes, proteins, structures, and interactions published daily in scientific journals, some problems are still observed in specific tasks such as functional annotation. The annotation of function is a critical issue for bioinformatic routines, such as for instance, in functional genomics and the further prediction of unknown protein function, which are highly dependent of the quality of existing annotations. Some information management systems evolve to efficiently incorporate information from large-scale projects, but often, annotation of single records from the literature is difficult and slow. In this short report, functional characterizations of a representative sample of the entire set of uncharacterized proteins from Escherichia coli K12 was compiled from Swiss-Prot, PubMed, and EcoCyc and demonstrate a functional annotation deficit in biological databases. Some issues are postulated as causes of the lack of annotation, and different solutions are evaluated and proposed to avoid them. The hope is that as a consequence of these observations, there will be new impetus to improve the speed and quality of functional annotation and ultimately provide updated, reliable information to the scientific community. PMID:20050264

  20. RASSF tumor suppressor gene family: biological functions and regulation.

    PubMed

    Volodko, Natalia; Gordon, Marilyn; Salla, Mohamed; Ghazaleh, Haya Abu; Baksh, Shairaz

    2014-08-19

    Genetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFκB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation. PMID:24607545

  1. Biomarkers of Aging: From Function to Molecular Biology

    PubMed Central

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-01-01

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products. PMID:27271660

  2. Biomarkers of Aging: From Function to Molecular Biology.

    PubMed

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-01-01

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products. PMID:27271660

  3. Density Functional Theory of Biologically Relevant Metal Centers

    NASA Astrophysics Data System (ADS)

    Siegbahn, Per E. M.; Blomberg, Margareta R. A.

    1999-10-01

    Recent applications of density functional theory to biologically relevant metal centers are reviewed. The emphasis is on reaction mechanisms, structures, and modeling. The accuracy of different functionals is discussed for standard benchmark tests of first- and second-row molecules and for transition metal systems. Modeling aspects of the protein metal complexes are discussed regarding both the size of the model being treated quantum mechanically and the treatment of the protein surrounding it. To illustrate the effects, structures computed without the effects of the protein are compared with experimental structures from enzymes, and results from simple dielectric models of the protein for electron transfer processes are described. The choice of spin state is discussed for multimetal complexes. Examples of mechanisms studied recently by density functional theory are described, such as O2 and methane activation in methane monooxygenase and O2 formation in photosystem II.

  4. PELP1: Structure, biological function and clinical significance.

    PubMed

    Sareddy, Gangadhara Reddy; Vadlamudi, Ratna K

    2016-07-01

    Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors. Notably, the PELP1 protein has a histone-binding domain, recognizes histone modifications and interacts with several chromatin-modifying complexes. PELP1 serves as a substrate of multitude of kinases, and phosphorylation regulates its functions in various complexes. Further, PELP1 plays essential roles in several pathways including hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response. PELP1 expression is upregulated in several cancers, its deregulation contributes to therapy resistance, and it is a prognostic biomarker for breast cancer survival. Recent evidence suggests that PELP1 represents a novel therapeutic target for many hormonal cancers. In this review, we summarized the emerging biological properties and functions of PELP1. PMID:26997260

  5. Systemic Modeling of Biological Functions in Consideration of Physiome Project

    NASA Astrophysics Data System (ADS)

    Minamitani, Haruyuki

    Emerging of the physiome project provides various influences on the medical, biological and pharmaceutical development. In this paper, as an example of physiome research, neural network model analysis providing the conduction mechanisms of pain and tactile sensations was presented, and the functional relations between neural activities of the network cells and stimulus intensity applied on the peripheral receptive fields were described. The modeling presented here is based on the various assumptions made by the results of physiological and anatomical studies reported in the literature. The functional activities of spinothalamic and thalamocortical cells show a good agreement with the physiological and psychophysical functions of somatosensory system that are very instructive for covering the gap between physiologically and psychophysically aspects of pain and tactile sensation.

  6. The Impact of Collective Molecular Dynamics on Physiological and Biological Functionalities of Artificial and Biological Membranes

    NASA Astrophysics Data System (ADS)

    Rheinstadter, Maikel

    2008-03-01

    We use neutron, X-ray and light scattering techniques to determine dynamical and structural properties of artificial and biological membranes. The combination of various techniques enlarges the window to length scales from the nearest-neighbor distances of lipid molecules to more than 10-6m, covering time scales from about 0.1 ps to 1 s. The main research objective is to quantify collective molecular fluctuations in these systems and to establish relationships to physiological and biological functions of the bilayers, such as transmembrane transport. The motivation for this project is twofold: 1) By understanding fundamental properties of bilayers at the microscopic and mesoscopic level, we aim to tailor membranes with specific properties such as permeability and elasticity. 2) By relating dynamical fluctuations to physiological and biological functions, we can gain a deeper understanding of the bilayers on a molecular scale that may help optimizing the transmembrane transport of certain drugs. We show how bilayer permeability, elasticity and inter protein excitations can be determined from the experiments. M.C. Rheinstädter et al., Phys. Rev. Lett. 93, 108107 (2004); Phys. Rev. Lett. 97, 048103 (2006); Phys. Rev. E 75, 011907 (2007);J. Vac. Soc. Technol. A 24, 1191 (2006).

  7. Accelerating expansion or inhomogeneity? II. Mimicking acceleration with the energy function in the Lemaître-Tolman model

    NASA Astrophysics Data System (ADS)

    Krasiński, Andrzej

    2014-07-01

    This is a continuation of the paper published in Phys. Rev. D 89, 023520 (2014). Here we investigate how the luminosity distance-redshift relation DL(z) of the ΛCDM model is duplicated in the Lemaître-Tolman (L-T) model with Λ =0, constant bang-time function tB and the energy function E(r) mimicking accelerated expansion on the observer's past light cone (r is a uniquely defined comoving radial coordinate). Numerical experiments show that E>0 necessarily. The functions z(r) and E(r) are numerically calculated from the initial point at the observer's position, then backward from the initial point at the apparent horizon (AH). Reconciling the results of the two calculations allows one to determine the values of E/r2 at r=0 and at the AH. The problems connected with continuing the calculation through the AH are discussed in detail and solved. Then z(r) and E(r) are continued beyond the AH, up to the numerical crash that signals the contact of the light cone with the big bang. Similarly, the light cone of the L-T model is calculated by proceeding from the two initial points, and compared with the ΛCDM light cone. The model constructed here contains shell crossings, but they can be removed by matching the L-T region to a Friedmann background, without causing any conflict with the type Ia supernovae observations. The mechanism of imitating the accelerated expansion by the E(r) function is explained in a descriptive way.

  8. Tubulin acetylation: responsible enzymes, biological functions and human diseases.

    PubMed

    Li, Lin; Yang, Xiang-Jiao

    2015-11-01

    Microtubules have important functions ranging from maintenance of cell morphology to subcellular transport, cellular signaling, cell migration, and formation of cell polarity. At the organismal level, microtubules are crucial for various biological processes, such as viral entry, inflammation, immunity, learning and memory in mammals. Microtubules are subject to various covalent modifications. One such modification is tubulin acetylation, which is associated with stable microtubules and conserved from protists to humans. In the past three decades, this reversible modification has been studied extensively. In mammals, its level is mainly governed by opposing actions of α-tubulin acetyltransferase 1 (ATAT1) and histone deacetylase 6 (HDAC6). Knockout studies of the mouse enzymes have yielded new insights into biological functions of tubulin acetylation. Abnormal levels of this modification are linked to neurological disorders, cancer, heart diseases and other pathological conditions, thereby yielding important therapeutic implications. This review summarizes related studies and concludes that tubulin acetylation is important for regulating microtubule architecture and maintaining microtubule integrity. Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function. PMID:26227334

  9. A Chemical Biology Approach to Developing STAT Inhibitors: Molecular Strategies for Accelerating Clinical Translation

    PubMed Central

    Nelson, Erik A.; Sharma, Sreenath V.; Settleman, Jeffrey; Frank, David A.

    2011-01-01

    STAT transcription factors transduce signals from the cell surface to the nucleus, where they regulate the expression of genes that control proliferation, survival, self-renewal, and other critical cellular functions. Under normal physiological conditions, the activation of STATs is tightly regulated. In cancer, by contrast, STAT proteins, particularly STAT3 and STAT5, become activated constitutively, thereby driving the malignant phenotype of cancer cells. Since these proteins are largely dispensable in the function of normal adult cells, STATs represent a potentially important target for cancer therapy. Although transcription factors have traditionally been viewed as suboptimal targets for pharmacological inhibition, chemical biology approaches have been particularly fruitful in identifying compounds that can modulate this pathway through a variety of mechanisms. STAT inhibitors have notable anti-cancer effects in many tumor systems, show synergy with other therapeutic modalities, and have the potential to eradicate tumor stem cells. Furthermore, STAT inhibitors identified through the screening of chemical libraries can then be employed in large scale analyses such as gene expression profiling, RNA interference screens, or large-scale tumor cell line profiling. Data derived from these studies can then provide key insights into mechanisms of STAT signal transduction, as well as inform the rational design of targeted therapeutic strategies for cancer patients. PMID:21680956

  10. Hyaluronan: A Simple Polysaccharide with Diverse Biological Functions

    PubMed Central

    Dicker, Kevin T.; Gurski, Lisa A.; Pradhan-Bhatt, Swati; Witt, Robert L.; Farach-Carson, Mary C.; Jia, Xinqiao

    2014-01-01

    Hyaluronan (HA) is a linear polysaccharide with disaccharide repeats of D-glucuronic acid and N-acetyl-D-glucosamine. It is evolutionary conserved and abundantly expressed in the extracellular matrix (ECM), on the cell surface and even inside cells. Being a simple polysaccharide, HA exhibits an astonishing array of biological functions. HA interacts with various proteins or proteoglycans to organize the ECM and to maintain tissue homeostasis. The unique physical and mechanical properties of HA contribute to the maintenance of tissue hydration, the mediation of solute diffusion through the extracellular space and the lubrication of certain tissues. The diverse biological functions of HA are manifested through its complex interactions with matrix components and resident cells. Binding of HA with cell surface receptors activates various signaling pathways that regulate cell function, tissue development, inflammation, wound healing and tumor progression and metastasis. Taking advantage of the inherent biocompatibility and biodegradability of HA, as well as its susceptibility to chemical modification, researchers have developed various HA-based biomaterials and tissue constructs with promising and broad clinical potential. In this article, we illustrate the properties of HA from a matrix biology perspective by first introducing principles underlying the biosynthesis and biodegradation of HA, as well as the interactions of HA with various proteins and proteoglycans. We next highlight the roles of HA in physiological and pathological states, including morphogenesis, wound healing and tumor metastasis. A deeper understanding of the mechanisms underlying the roles of HA in various physiological processes can provide new insights and tools for the engineering of complex tissues and tissue models. PMID:24361428

  11. Functional magnetic resonance imaging for defining the biological target volume

    PubMed Central

    Kauczor, Hans-Ulrich; Zechmann, Christian; Stieltjes, Bram; Weber, Marc-Andre

    2006-01-01

    Morphology as demonstrated by CT is the basis for radiotherapy planning. Intensity-modulated and adaptive radiotherapy techniques would greatly benefit from additional functional information allowing for definition of the biological target volume. MRI techniques include several which can characterize and quantify different tissue properties and their tumour-related changes. Results of perfusion MRI represent microvascular density and permeability; MR spectroscopy depicts particular metabolites; diffusion weighted imaging shows tissue at risk and tumour cellularity; while dynamic 3D acquisition (4D MRI) shows organ motion and the mobility of tumours within them. PMID:16766269

  12. Structure and Biological Functions of β-Hairpin Antimicrobial Peptides

    PubMed Central

    Panteleev, P. V.; Bolosov, I. A.; Balandin, S. V.; Ovchinnikova, T. V.

    2015-01-01

    Antimicrobial peptides (AMPs) are evolutionarily ancient factors of the innate immune system that serve as a crucial first line of defense for humans, animals, and plants against infection. This review focuses on the structural organization, biosynthesis, and biological functions of AMPs that possess a β-hairpin spatial structure. Representatives of this class of AMPs are among the most active antibiotic molecules of animal origin. Due to their wide spectrum of activity and resistance to internal environmental factors, natural β-hairpin AMPbased compounds might become the most promising drug candidates. PMID:25927000

  13. Functionalization of polydopamine coated magnetic nanoparticles with biological entities

    NASA Astrophysics Data System (ADS)

    Mǎgeruşan, Lidia; Mrówczyński, Radosław; Turcu, Rodica

    2015-12-01

    New hybrid materials, obtained through introduction of cysteine, lysine and folic acid as biological entities into polydopamine-coated magnetite nanoparticles, are reported. The syntheses are straight forward and various methods were applied for structural and morphological characterization of the resulting nanoparticles. XPS proved a very powerful tool for surface chemical analysis and it evidences the functionalization of polydopamine coated magnetite nanoparticles. The superparamagnetic behavior and the high values of saturation magnetization recommend all products for further application where magnetism is important for targeting, separation, or heating by alternative magnetic fields.

  14. Suboptimal geometrical implantation of biological aortic valves provokes functional deficits.

    PubMed

    Kuehnel, Ralf-Uwe; Wendt, Max O; Jainski, Ute; Hartrumpf, Martin; Pohl, Manfred; Albes, Johannes M

    2010-06-01

    Endovascular valves have become a valid option for patients not qualifying for conventional surgery. Biological valves mounted in a stent are currently used. After implantation, however, geometrical distortion of the valve can occur. We tested whether biological valves suitable for transcatheter implantation exhibit hemodynamic deficits after deployment in a distorted position. Two types of valves [bovine pericardium (BP) and porcine cusps], of 21 and 23 mm diameter, respectively were investigated. Mean transvalvular gradient (TVG), effective orifice area (EOA), and regurgitation fraction (REG) were measured prior to and after the 20% distortion of the original diameter. All valves exhibited an increase of TVG and reduction of EOA whereas REG increased only in BP valves after distortion. The 21 mm valves demonstrated a more pronounced alteration than the 23 mm valves. Even moderately distorted implantation of a biological valve results in a marked functional alteration. The susceptibility of pericardial valves is higher than that of porcine valves probably owing to better coaptation properties of native cusps even under deformed conditions when compared to valves constructed with pericardium. Care should therefore be taken during implantation of endovascular valves in order to avoid fixed hemodynamic deficits. Native valves may preferably be used as they demonstrate a more robust behavior regarding suboptimal implantation. PMID:20233809

  15. An acceleration transducer based on optical fiber Bragging grating with temperature self-compensating function

    NASA Astrophysics Data System (ADS)

    Wang, Chuan; Lu, Qiyu; Ou, Jinping

    2013-04-01

    Along with the maturity and development of Optical Fiber Bragg Grating (OFBG) sensing technology, OFBG sensors with different functions have been developed and applied in large-scale engineering structure health monitoring and construction monitoring. In this paper, an acceleration transducer with a characteristic of temperature self-compensating is introduced. It is a cantilever structure model with equal strength beam, fixed with a mass block at the end of the beam, and two consecutive OFBGs are pasted on the upper and lower surface axis of the beam at the corresponding places. Because of the two OFBGs are near to each other, the wavelength changes caused by the environment temperature is the same. According to the temperature self-compensating principle and acceleration measurement principle developed in this paper, we can achieve the temperature self-compensating function of real acceleration measurement by simply calculating the test results. The experimental results show that this type of acceleration transducer has high sensitivity and stability and its measuring range can also be changed according to the practical requirements. This type of acceleration transducer is suitable for engineering structure acceleration measurement in different environment conditions.

  16. Functions of microRNAs in cardiovascular biology and disease.

    PubMed

    Hata, Akiko

    2013-01-01

    In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology. PMID:23157557

  17. Diffusion of innovations dynamics, biological growth and catenary function

    NASA Astrophysics Data System (ADS)

    Guseo, Renato

    2016-12-01

    The catenary function has a well-known role in determining the shape of chains and cables supported at their ends under the force of gravity. This enables design using a specific static equilibrium over space. Its reflected version, the catenary arch, allows the construction of bridges and arches exploiting the dual equilibrium property under uniform compression. In this paper, we emphasize a further connection with well-known aggregate biological growth models over time and the related diffusion of innovation key paradigms (e.g., logistic and Bass distributions over time) that determine self-sustaining evolutionary growth dynamics in naturalistic and socio-economic contexts. Moreover, we prove that the 'local entropy function', related to a logistic distribution, is a catenary and vice versa. This special invariance may be explained, at a deeper level, through the Verlinde's conjecture on the origin of gravity as an effect of the entropic force.

  18. Current studies on physiological functions and biological production of lactosucrose.

    PubMed

    Mu, Wanmeng; Chen, Qiuming; Wang, Xiao; Zhang, Tao; Jiang, Bo

    2013-08-01

    Lactosucrose (O-β-D-galactopyranosyl-(1,4)-O-α-D-glucopyranosyl-(1,2)-β-D-fructofuranoside) is a trisaccharide formed from lactose and sucrose by enzymatic transglycosylation. This rare trisaccharide is a kind of indigestible carbohydrate, has good prebiotic effect, and promotes intestinal mineral absorption. It has been used as a functional ingredient in a range of food products which are approved as foods for specified health uses in Japan. Using lactose and sucrose as substrates, lactosucrose can be produced through transfructosylation by β-fructofuranosidase from Arthrobacter sp. K-1 or a range of levansucrases, or through transgalactosylation by β-galactosidase from Bacillus circulans. This article presented a review of recent studies on the physiological functions of lactosucrose and the biological production from lactose and sucrose by different enzymes. PMID:23828605

  19. Event-based text mining for biology and functional genomics.

    PubMed

    Ananiadou, Sophia; Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B

    2015-05-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of 'events', i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

  20. Sucrose metabolism gene families and their biological functions

    PubMed Central

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-01-01

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

  1. Event-based text mining for biology and functional genomics

    PubMed Central

    Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

    2015-01-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

  2. Head and Tibial Acceleration as a Function of Stride Frequency and Visual Feedback during Running

    PubMed Central

    Busa, Michael A.; Lim, Jongil; van Emmerik, Richard E. A.; Hamill, Joseph

    2016-01-01

    Individuals regulate the transmission of shock to the head during running at different stride frequencies although the consequences of this on head-gaze stability remain unclear. The purpose of this study was to examine if providing individuals with visual feedback of their head-gaze orientation impacts tibial and head accelerations, shock attenuation and head-gaze motion during preferred speed running at different stride frequencies. Fifteen strides from twelve recreational runners running on a treadmill at their preferred speed were collected during five stride frequencies (preferred, ±10% and ±20% of preferred) in two visual task conditions (with and without real-time visual feedback of head-gaze orientation). The main outcome measures were tibial and head peak accelerations assessed in the time and frequency domains, shock attenuation from tibia to head, and the magnitude and velocity of head-gaze motion. Decreasing stride frequency resulted in greater vertical accelerations of the tibia (p<0.01) during early stance and at the head (p<0.01) during early and late stance; however, for the impact portion the increase in head acceleration was only observed for the slowest stride frequency condition. Visual feedback resulted in reduced head acceleration magnitude (p<0.01) and integrated power spectral density in the frequency domain (p<0.01) in late stance, as well as overall of head-gaze motion (p<0.01). When running at preferred speed individuals were able to stabilize head acceleration within a wide range of stride frequencies; only at a stride frequency 20% below preferred did head acceleration increase. Furthermore, impact accelerations of the head and tibia appear to be solely a function of stride frequency as no differences were observed between feedback conditions. Increased visual task demands through head gaze feedback resulted in reductions in head accelerations in the active portion of stance and increased head-gaze stability. PMID:27271850

  3. Relative biological effectiveness of accelerated heavy ions for induction of morphological transformation in Syrian hamster embryo cells.

    PubMed

    Han, Z B; Suzuki, H; Suzuki, F; Suzuki, M; Furusawa, Y; Kato, T; Ikenaga, M

    1998-09-01

    Syrian hamster embryo cells were used to study the morphological transformation induced by accelerated heavy ions with different linear energy transfer (LET) ranging from 13 to 400 keV/micron. Exponentially growing cells were irradiated with 12C or 28Si ion beams generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC), then inoculated to culture dishes. Morphologically altered colonies were scored as transformants. Over the LET range examined, the frequency of transformation induced by the heavy ions increased sharply at very low doses no greater than 5 cGy. The relative biological effectiveness (RBE) of the heavy ions relative to X-rays first increased with LET, reached a maximum value of about 7 at 100 keV/micron, then decreased with the further increase of LET. Our findings confirmed that high LET heavy ions are much more effective than X-rays for the induction of in vitro cell transformation. PMID:9868868

  4. Nitrogen compounds in wine during its biological aging by two flor film yeasts: An approach to accelerated biological aging of dry sherry-type wines.

    PubMed

    Mauricio, J C; Ortega, J M

    1997-01-20

    Urea, ammonium, and free amino acid contents were quantified in biological aging of a young wine under two flor film forming yeast strains, Saccharomyces cerevisiae race capensis and S. cerevisiae race bayanus, and compared. Cell viability in the film was different for the two yeast strains. Thus, capensis maintained a much greater number of viable cells per surface area than bayanus and hence used greater amount of nitrogen compounds. The main source of nitrogen for the yeasts during the biological aging process was L-proline. The two yeast strains also differed in the amounts of assimilable nitrogen they utilized, in their preferences for amino acid consumption, and kinetics. To accelerate the aging process, the effect of controlled monthly aeration of the wine aged with capensis strain was investigated. The results revealed that short aeration did not appreciably increase the overall consumption of assimilable nitrogen, but consumption of some nitrogen compounds was accelerated (particularly L-proline, L-tryptophan, L-glutamic acid, ammonium ion, L-lysine, and L-arginine); the use of L-ornithine was inhibited; and GABA, L-methionine, and urea were depletes. Probably the aeration increases the aroma compounds, thereby producing wines with improved sensory properties. (c) 1997 John Wiley & Sons, Inc. PMID:18633960

  5. DIFFUSIVE PARTICLE ACCELERATION IN SHOCKED, VISCOUS ACCRETION DISKS: GREEN'S FUNCTION ENERGY DISTRIBUTION

    SciTech Connect

    Becker, Peter A.; Das, Santabrata; Le, Truong E-mail: sbdas@iitg.ernet.in

    2011-12-10

    The acceleration of relativistic particles in a viscous accretion disk containing a standing shock is investigated as a possible explanation for the energetic outflows observed around radio-loud black holes. The energy/space distribution of the accelerated particles is computed by solving a transport equation that includes the effects of first-order Fermi acceleration, bulk advection, spatial diffusion, and particle escape. The velocity profile of the accreting gas is described using a model for shocked viscous disks recently developed by the authors, and the corresponding Green's function distribution for the accelerated particles in the disk and the outflow is obtained using a classical method based on eigenfunction analysis. The accretion-driven, diffusive shock acceleration scenario explored here is conceptually similar to the standard model for the acceleration of cosmic rays at supernova-driven shocks. However, in the disk application, the distribution of the accelerated particles is much harder than would be expected for a plane-parallel shock with the same compression ratio. Hence the disk environment plays a key role in enhancing the efficiency of the shock acceleration process. The presence of the shock helps to stabilize the disk by reducing the Bernoulli parameter, while channeling the excess binding energy into the escaping relativistic particles. In applications to M87 and Sgr A*, we find that the kinetic power in the jet is {approx}0.01 M-dot c{sup 2}, and the outflowing relativistic particles have a mean energy {approx}300 times larger than that of the thermal gas in the disk at the shock radius. Our results suggest that a standing shock may be an essential ingredient in accretion onto underfed black holes, helping to resolve the long-standing problem of the stability of advection-dominated accretion disks.

  6. Students' Perceptions of Long-Functioning Cooperative Teams in Accelerated Adult Degree Programs

    ERIC Educational Resources Information Center

    Favor, Judy

    2012-01-01

    This study examined 718 adult students' perceptions of long-functioning cooperative study teams in accelerated associate's, bachelor's, and master's business degree programs. Six factors were examined: attraction toward team, alignment of performance expectations, intrateam conflict, workload sharing, preference for teamwork, and impact on…

  7. Androgen Receptor Structure, Function and Biology: From Bench to Bedside

    PubMed Central

    Davey, Rachel A; Grossmann, Mathis

    2016-01-01

    The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nuclear receptor family. Given its widespread expression in many cells and tissues, the AR has a diverse range of biological actions including important roles in the development and maintenance of the reproductive, musculoskeletal, cardiovascular, immune, neural and haemopoietic systems. AR signalling may also be involved in the development of tumours in the prostate, bladder, liver, kidney and lung. Androgens can exert their actions via the AR in a DNA binding-dependent manner to regulate target gene transcription, or in a non-DNA binding-dependent manner to initiate rapid, cellular events such as the phosphorylation of 2nd messenger signalling cascades. More recently, ligand-independent actions of the AR have also been identified. Given the large volume of studies relating to androgens and the AR, this review is not intended as an extensive review of all studies investigating the AR, but rather as an overview of the structure, function, signalling pathways and biology of the AR as well as its important role in clinical medicine, with emphasis on recent developments in this field. PMID:27057074

  8. AFM imaging of functionalized carbon nanotubes on biological membranes

    NASA Astrophysics Data System (ADS)

    Lamprecht, C.; Liashkovich, I.; Neves, V.; Danzberger, J.; Heister, E.; Rangl, M.; Coley, H. M.; McFadden, J.; Flahaut, E.; Gruber, H. J.; Hinterdorfer, P.; Kienberger, F.; Ebner, A.

    2009-10-01

    Multifunctional carbon nanotubes are promising for biomedical applications as their nano-size, together with their physical stability, gives access into the cell and various cellular compartments including the nucleus. However, the direct and label-free detection of carbon nanotube uptake into cells is a challenging task. The atomic force microscope (AFM) is capable of resolving details of cellular surfaces at the nanometer scale and thus allows following of the docking of carbon nanotubes to biological membranes. Here we present topographical AFM images of non-covalently functionalized single walled (SWNT) and double walled carbon nanotubes (DWNT) immobilized on different biological membranes, such as plasma membranes and nuclear envelopes, as well as on a monolayer of avidin molecules. We were able to visualize DWNT on the nuclear membrane while at the same time resolving individual nuclear pore complexes. Furthermore, we succeeded in localizing individual SWNT at the border of incubated cells and in identifying bundles of DWNT on cell surfaces by AFM imaging.

  9. Biologically functionalized nanochannels on ferroelectric lead zirconium titanate surfaces.

    SciTech Connect

    Ocola, L. E.; Pan, W. C.; Kuo, M.; Tirumala, V. R.; Reiss, B. D.; Firestone, M. A.; Illinois Mathematics and Science Academy

    2005-01-01

    We recently started a program at Argonne to exploit patterned, polarizable ferroelectric surfaces, such as lead zirconium titanate (PZT), as a means to create field-responsive inorganic-biomolecule interfaces to study and manipulate biomatter on surfaces. In this paper we will discuss the integration of nanochannels on the surface of PZT films and their selective functionalization to create nanovalves to control nanofluidic flow. Microfluidic devices have been fabricated using a variety of methods, ranging from thermal decomposition of buried patterned channels, to fabricating trenches via plasma etch or hot embossing followed by trench capping. Our work focuses on an alternative method by using a bilayer resist in an inverted configuration normally used for T- and Gamma- gate fabrication. This method is capable of yielding sub-100 nm nanochannels with high aspect ratios and sub-500nm alignment. We have recently demonstrated that the polarization hysteresis loop of PZT is the same before and after exposure to an aqueous environment. This opens the possibility of selective surface modification of PZT via coupling of a wide range of biomolecules (e.g., peptides, proteins) and the use of the electric-field-responsive properties of PZT to manipulate the function (e.g., orientation) of the tethered biomolecules. We have used phage display techniques to evolve specific peptide motifs that selectively bind to PZT. The optimum heptapeptide that facilitates both the attachment of functional biological molecules to the surface of PZT has been identified.

  10. Linking biological soil crust diversity to ecological functions

    NASA Astrophysics Data System (ADS)

    Glaser, Karin; Borchhardt, Nadine; Schulz, Karoline; Mikhailyuk, Tatiana; Baumann, Karen; Leinweber, Peter; Ulf, Karsten

    2016-04-01

    Biological soil crusts (BSCs) are an association of different microorganisms and soil particles in the top millimeters of the soil. They are formed by algae, cyanobacteria, microfungi, bacteria, bryophytes and lichens in various compositions. Our aim was to determine and compare the biodiversity of all occurring organisms in biogeographically different habitats, ranging from polar (both Arctic and Antarctic), subpolar (Scandinavia), temperate (Germany) to dry regions (Chile). The combination of microscopy and molecular techniques (next-generation sequencing) revealed highly diverse crust communities, whose composition clustered by region and correlates with habitat characteristics such as water content. The BSC biodiversity was then linked to the ecological function of the crusts. The functional role of the BSCs in the biogeochemical cycles of carbon, nitrogen and phosphorous is evaluated using an array of state of the art soil chemistry methods including Py-FIMS (pyrolysis field ionization mass spectrometry) and XANES (x-ray absorbance near edge structure). Total P as well as P fractions were quantified in all BSCs, adjacent soil underneath and comparable nearby soil of BSC-free areas revealing a remarkable accumulation of total phosphorous and a distinct pattern of P fractions in the crust. Further, we observed an indication of a different P-speciation composition in the crust compared with BSC-free soil. The data allow answering the question whether BSCs act as sink or source for these compounds, and how biodiversity controls the biogeochemical function of BSCs.

  11. Genome-wide survey for biologically functional pseudogenes.

    PubMed

    Svensson, Orjan; Arvestad, Lars; Lagergren, Jens

    2006-05-01

    According to current estimates there exist about 20,000 pseudogenes in a mammalian genome. The vast majority of these are disabled and nonfunctional copies of protein-coding genes which, therefore, evolve neutrally. Recent findings that a Makorin1 pseudogene, residing on mouse Chromosome 5, is, indeed, in vivo vital and also evolutionarily preserved, encouraged us to conduct a genome-wide survey for other functional pseudogenes in human, mouse, and chimpanzee. We identify to our knowledge the first examples of conserved pseudogenes common to human and mouse, originating from one duplication predating the human-mouse species split and having evolved as pseudogenes since the species split. Functionality is one possible way to explain the apparently contradictory properties of such pseudogene pairs, i.e., high conservation and ancient origin. The hypothesis of functionality is tested by comparing expression evidence and synteny of the candidates with proper test sets. The tests suggest potential biological function. Our candidate set includes a small set of long-lived pseudogenes whose unknown potential function is retained since before the human-mouse species split, and also a larger group of primate-specific ones found from human-chimpanzee searches. Two processed sequences are notable, their conservation since the human-mouse split being as high as most protein-coding genes; one is derived from the protein Ataxin 7-like 3 (ATX7NL3), and one from the Spinocerebellar ataxia type 1 protein (ATX1). Our approach is comparative and can be applied to any pair of species. It is implemented by a semi-automated pipeline based on cross-species BLAST comparisons and maximum-likelihood phylogeny estimations. To separate pseudogenes from protein-coding genes, we use standard methods, utilizing in-frame disablements, as well as a probabilistic filter based on Ka/Ks ratios. PMID:16680195

  12. Comparative genomics of pectinacetylesterases: Insight on function and biology

    PubMed Central

    de Souza, Amancio José; Pauly, Markus

    2015-01-01

    Pectin acetylation influences the gelling ability of this important plant polysaccharide for the food industry. Plant apoplastic pectinacetylesterases (PAEs) play a key role in regulating the degree of pectin acetylation and modifying their expression thus represents one way to engineer plant polysaccharides for food applications. Identifying the major active enzymes within the PAE gene family will aid in our understanding of this biological phenomena as well as provide the tools for direct trait manipulation. Using comparative genomics we propose that there is a minimal set of 4 distinct PAEs in plants. Possible functional diversification of the PAE family in the grasses is also explored with the identification of 3 groups of PAE genes specific to grasses. PMID:26237162

  13. Comparative genomics of pectinacetylesterases: Insight on function and biology.

    PubMed

    de Souza, Amancio José; Pauly, Markus

    2015-01-01

    Pectin acetylation influences the gelling ability of this important plant polysaccharide for the food industry. Plant apoplastic pectinacetylesterases (PAEs) play a key role in regulating the degree of pectin acetylation and modifying their expression thus represents one way to engineer plant polysaccharides for food applications. Identifying the major active enzymes within the PAE gene family will aid in our understanding of this biological phenomena as well as provide the tools for direct trait manipulation. Using comparative genomics we propose that there is a minimal set of 4 distinct PAEs in plants. Possible functional diversification of the PAE family in the grasses is also explored with the identification of 3 groups of PAE genes specific to grasses. PMID:26237162

  14. Update on the functional biology of Lrrk2.

    PubMed

    Melrose, Heather

    2008-01-01

    The etiology of Parkinson's disease (PD) was long thought to be due to environmental factors. Following the discovery of autosomal-dominant mutations in the α-synuclein gene, and later recessive mutations in the DJ-1, Parkin and PINK-1 genes, the field of PD genetics exploded. In 2004, it was discovered that mutations in the PARK8 locus - leucine-rich repeat kinase 2 (LRRK2, Lrrk2) - are the most important genetic cause of autosomal-dominant PD. Lrrk2 substitutions also account for sporadic PD in certain ethnic populations and have been shown to increase the risk of PD in Asian populations. Drug therapies targeting Lrrk2 activity may therefore be beneficial to both familial and sporadic PD patients, hence understanding the role of Lrrk2 in health and disease is critical. This review aims to highlight the research effort concentrated on elucidating the functional biological role of Lrrk2, and to provide some future therapeutic perspectives. PMID:19225574

  15. Biochemical Properties and Biological Functions of FET Proteins.

    PubMed

    Schwartz, Jacob C; Cech, Thomas R; Parker, Roy R

    2015-01-01

    Members of the FET protein family, consisting of FUS, EWSR1, and TAF15, bind to RNA and contribute to the control of transcription, RNA processing, and the cytoplasmic fates of messenger RNAs in metazoa. FET proteins can also bind DNA, which may be important in transcription and DNA damage responses. FET proteins are of medical interest because chromosomal rearrangements of their genes promote various sarcomas and because point mutations in FUS or TAF15 can cause neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar dementia. Recent results suggest that both the normal and pathological effects of FET proteins are modulated by low-complexity or prion-like domains, which can form higher-order assemblies with novel interaction properties. Herein, we review FET proteins with an emphasis on how the biochemical properties of FET proteins may relate to their biological functions and to pathogenesis. PMID:25494299

  16. Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology

    PubMed Central

    Balakrishnan, Sri Kripa; Witcher, Michael; Berggren, Travis W.; Emerson, Beverly M.

    2012-01-01

    The CCCTC-binding factor CTCF is the only known vertebrate insulator protein and has been shown to regulate important developmental processes such as imprinting, X-chromosome inactivation and genomic architecture. In this study, we examined the role of CTCF in human embryonic stem cell (hESC) biology. We demonstrate that CTCF associates with several important pluripotency genes, including NANOG, SOX2, cMYC and LIN28 and is critical for hESC proliferation. CTCF depletion impacts expression of pluripotency genes and accelerates loss of pluripotency upon BMP4 induced differentiation, but does not result in spontaneous differentiation. We find that CTCF associates with the distal ends and internal sites of the co-regulated 160 kb NANOG-DPPA3-GDF3 locus. Each of these sites can function as a CTCF-dependent enhancer-blocking insulator in heterologous assays. In hESCs, CTCF exists in multisubunit protein complexes and can be poly(ADP)ribosylated. Known CTCF cofactors, such as Cohesin, differentially co-localize in the vicinity of specific CTCF binding sites within the NANOG locus. Importantly, the association of some cofactors and protein PARlation selectively changes upon differentiation although CTCF binding remains constant. Understanding how unique cofactors may impart specialized functions to CTCF at specific genomic locations will further illuminate its role in stem cell biology. PMID:22879976

  17. Functionalized nanoparticles for biological imaging and detection applications

    NASA Astrophysics Data System (ADS)

    Mei, Bing C.

    Semiconductor quantum dots (QDs) and gold nanoparticles (AuNPs) have gained tremendous attention in the last decade as a result of their size-dependent spectroscopic properties. These nanoparticles have been a subject of intense study to bridge the gap between macroscopic and atomic behavior, as well as to generate new materials for novel applications in therapeutics, biological sensing, light emitting devices, microelectronics, lasers, and solar cells. One of the most promising areas for the use of these nanoparticles is in biotechnology, where their size-dependent optical properties are harnessed for imaging and sensing applications. However, these nanoparticles, as synthesized, are often not stable in aqueous media and lack simple and reliable means of covalently linking to biomolecules. The focus of this work is to advance the progress of these nanomaterials for biotechnology by synthesizing them, characterizing their optical properties and rendering them water-soluble and functional while maintaining their coveted optical properties. QDs were synthesized by an organometallic chemical procedure that utilizes coordinating solvents to provide brightly luminescent nanoparticles. The optical interactions of these QDs were studied as a function of concentration to identify particle size-dependent optimal concentrations, where scattering and indirection excitation are minimized and the amount light observed per particle is maximized. Both QDs and AuNPs were rendered water-soluble and stable in a broad range of biologically relevant conditions by using a series of ligands composed of dihydrolipoic acid (DHLA) appended to poly(ethylene glycol) methyl ether. By studying the stability of the surface modified AuNPs, we revealed some interesting information regarding the role of the surface ligand on the nanoparticle stability (i.e. solubility in high salt concentration, resistance to dithiothreitol competition and cyanide decomposition). Furthermore, the nanoparticles

  18. Steroid receptor RNA activator: Biologic function and role in disease.

    PubMed

    Liu, Chan; Wu, Hong-Tao; Zhu, Neng; Shi, Ya-Ning; Liu, Zheng; Ao, Bao-Xue; Liao, Duan-Fang; Zheng, Xi-Long; Qin, Li

    2016-08-01

    Steroid receptor RNA activator (SRA) is a type of long noncoding RNA (lncRNA) which coordinates the functions of various transcription factors, enhances steroid receptor-dependent gene expression, and also serves as a distinct scaffold. The novel, profound and expanded roles of SRA are emerging in critical aspects of coactivation of nuclear receptors (NRs). As a nuclear receptor coactivator, SRA can coactivate androgen receptor (AR), estrogen receptor α (ERα), ERβ, progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptor and retinoic acid receptor (RAR). Although SRA is one of the least well-understood molecules, increasing studies have revealed that SRA plays a key role in both biological processes, such as myogenesis and steroidogenesis, and pathological changes, including obesity, cardiomyopathy, and tumorigenesis. Furthermore, the SRA-related signaling pathways, such as the mitogen-activated protein kinase (p38 MAPK), Notch and tumor necrosis factor α (TNFα) pathways, play critical roles in the pathogenesis of estrogen-dependent breast cancers. In addition, the most recent data demonstrates that SRA expression may serve as a new prognostic marker in patients with ER-positive breast cancer. Thus, elucidating the molecular mechanisms underlying SRA-mediated functions is important to develop proper novel strategies to target SRA in the diagnosis and treatment of human diseases. PMID:27282881

  19. Functional Skeletal Muscle Formation with a Biologic Scaffold

    PubMed Central

    Valentin, Jolene E.; Turner, Neill J.; Gilbert, Thomas W.; Badylak, Stephen F.

    2010-01-01

    Biologic scaffolds composed of extracellular matrix (ECM) have been used to reinforce or replace damaged or missing musculotendinous tissues in both preclinical studies and in human clinical applications. However, most studies have focused upon morphologic endpoints and few studies have assessed the in-situ functionality of newly formed tissue; especially new skeletal muscle tissue. The objective of the present study was to determine both the in-situ tetanic contractile response and histomorphologic characteristics of skeletal muscle tissue reconstructed using one of four test articles in a rodent abdominal wall model: 1) porcine small intestinal submucosa (SIS)-ECM; 2) carbodiimide-crosslinked porcine SIS-ECM; 3) autologous tissue; or 4) polypropylene mesh. Six months after surgery, the remodeled SIS-ECM showed almost complete replacement by islands and sheets of skeletal muscle, which generated a similar maximal contractile force to native tissue but with greater resistance to fatigue. The autologous tissue graft was replaced by a mixture of collagenous connective tissue, adipose tissue with fewer islands of skeletal muscle compared to SIS-ECM and a similar fatigue resistance to native muscle. Carbodiimide-crosslinked SIS-ECM and polypropylene mesh were characterized by a chronic inflammatory response and produced little or no measureable tetanic force. The findings of this study show that non-crosslinked xenogeneic SIS scaffolds and autologous tissue are associated with the restoration of functional skeletal muscle with histomorphologic characteristics that resemble native muscle. PMID:20638716

  20. Polysaccharide Immunomodulators as Therapeutic Agents: Structural Aspects and Biologic Function

    PubMed Central

    Tzianabos, Arthur O.

    2000-01-01

    Polysaccharide immunomodulators were first discovered over 40 years ago. Although very few have been rigorously studied, recent reports have revealed the mechanism of action and structure-function attributes of some of these molecules. Certain polysaccharide immunomodulators have been identified that have profound effects in the regulation of immune responses during the progression of infectious diseases, and studies have begun to define structural aspects of these molecules that govern their function and interaction with cells of the host immune system. These polymers can influence innate and cell-mediated immunity through interactions with T cells, monocytes, macrophages, and polymorphonuclear lymphocytes. The ability to modulate the immune response in an appropriate way can enhance the host's immune response to certain infections. In addition, this strategy can be utilized to augment current treatment regimens such as antimicrobial therapy that are becoming less efficacious with the advent of antibiotic resistance. This review focuses on recent studies that illustrate the structural and biologic activities of specific polysaccharide immunomodulators and outlines their potential for clinical use. PMID:11023954

  1. Evidence for Accelerated Decline of Functional Brain Network Efficiency in Schizophrenia.

    PubMed

    Sheffield, Julia M; Repovs, Grega; Harms, Michael P; Carter, Cameron S; Gold, James M; MacDonald, Angus W; Ragland, J Daniel; Silverstein, Steven M; Godwin, Douglass; Barch, Deanna M

    2016-05-01

    Previous work suggests that individuals with schizophrenia display accelerated aging of white matter integrity, however, it is still unknown whether functional brain networks also decline at an elevated rate in schizophrenia. Given the known degradation of functional connectivity and the normal decline in cognitive functioning throughout healthy aging, we aimed to test the hypothesis that efficiency of large-scale functional brain networks supporting overall cognition, as well as integrity of hub nodes within those networks, show evidence of accelerated aging in schizophrenia. Using pseudo-resting state data in 54 healthy controls and 46 schizophrenia patients, in which task-dependent signal from 3 tasks was regressed out to approximate resting-state data, we observed a significant diagnosis by age interaction in the prediction of both global and local efficiency of the cingulo-opercular network, and of the local efficiency of the fronto-parietal network, but no interaction when predicting both default mode network and whole brain efficiency. We also observed a significant diagnosis by age interaction for the node degree of the right anterior insula, left dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex. All interactions were driven by stronger negative associations between age and network metrics in the schizophrenia group than the healthy controls. These data provide evidence that is consistent with accelerated aging of large-scale functional brain networks in schizophrenia that support higher-order cognitive ability. PMID:26472685

  2. Electron distribution function behavior during localized transverse ion acceleration events in the topside auroral zone

    NASA Technical Reports Server (NTRS)

    Lynch, K. A.; Arnoldy, R. L.; Kintner, P. M.; Vago, J. L.

    1994-01-01

    The Topaz3 auroral sounding rocket made the following observations concerning the transfer of precipitating auroral electron energy to transverse ion acceleration in the topside auroral zone. During the course of the flight, the precipitating electron beam was modified to varying degrees by interaction with VLF hiss, at times changing the beam into a field-aligned plateau. The electron distribution functions throughout the flight are classified according to the extent of this modification, and correspondences with ion acceleration events are sought. The hiss power during most of this rocket flight apparently exceeded the threshold for collapse into solitary structures. At the times of plateaued electron distributions, the collapse of these structures was limited by Landau damping through the ambient ions, resulting in a velocity-dependent acceleration of both protons and oxygen. This initial acceleration is sufficient to supply the number flux of upflowing ions observed at satellite altitudes. The bursty ion acceleration was anticorrelated, on 1-s or smaller timescales, with dispersive bursts of precipitating field-aligned electrons, although on longer timescales the bursty ions and the bursty electrons are correlated.

  3. Exploring the mechanical basis for acceleration: pelvic limb locomotor function during accelerations in racing greyhounds (Canis familiaris).

    PubMed

    Williams, S B; Usherwood, J R; Jespers, K; Channon, A J; Wilson, A M

    2009-02-01

    Animals in their natural environments are confronted with a regular need to perform rapid accelerations (for example when escaping from predators or chasing prey). Such acceleration requires net positive mechanical work to be performed on the centre of mass by skeletal muscle. Here we determined how pelvic limb joints contribute to the mechanical work and power that are required for acceleration in galloping quadrupeds. In addition, we considered what, if any, biomechanical strategies exist to enable effective acceleration to be achieved. Simultaneous kinematic and kinetic data were collected for racing greyhounds undergoing a range of low to high accelerations. From these data, joint moments and joint powers were calculated for individual hindlimb joints. In addition, the mean effective mechanical advantage (EMA) of the limb and the ;gear ratio' of each joint throughout stance were calculated. Greatest increases in joint work and power with acceleration appeared at the hip and hock joints, particularly in the lead limb. Largest increases in absolute positive joint work occurred at the hip, consistent with the hypothesis that quadrupeds power locomotion by torque about the hip. In addition, hindlimb EMA decreased substantially with increased acceleration - a potential strategy to increase stance time and thus ground impulses for a given peak force. This mechanism may also increase the mechanical advantage for applying the horizontal forces necessary for acceleration. PMID:19181903

  4. Polymer biomaterial constructs for regenerative medicine and functional biological systems

    NASA Astrophysics Data System (ADS)

    Meng, Linghui

    The use of collagen as a biomaterial is currently undergoing a renaissance in the tissue engineering field. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenicity, make collagen a primary material resource in medical applications. Described herein is work towards the development of novel collagen-based matrices, with additional multi-functionality imparted through a novel in-situ crosslinking approach. The process of electrospinning has become a widely used technique for the creation of fibrous scaffolds for tissue engineering applications due to its ability to rapidly create structures composed of nano-scale polymer fibers closely resembling the architecture of the extracellular matrix (ECM). Collagen-PCL sheath-core bicomponent fibrous scaffolds were fabricated using a novel variation on traditional electrospinning, known as co-axial electrospinning. The results showed that the addition of a synthetic polymer core into collagen nanofibers remarkably increased the mechanical strength of collagen matrices spun from the benign solvent system. A novel single-step, in-situ collagen crosslink approach was developed in order to solve the problems dominating traditional collagen crosslinking methods, such as dimensional shrinking and loss of porous morphology, and to simplify the crosslinking procedure for electrospun collagen scaffolds. The excess amount of NHS present in the crosslinking mixture was found to delay the EDC/collagen coupling reaction in a controlled fashion. Fundamental investigations into the development and characterization of in-situ crosslinked collagen matrices such as fibrous scaffolds, gels and sponges, as well as their biomedical applications including cell culture substrates, wound dressings, drug delivery matrices and bone regeneration substitutes, were performed. The preliminary mice studies indicated that the in-situ crosslinked collagen matrices could be good candidates

  5. Accelerated Integrated Science Sequence (AISS): An Introductory Biology, Chemistry, and Physics Course

    ERIC Educational Resources Information Center

    Purvis-Roberts, Kathleen L.; Edwalds-Gilbert, Gretchen; Landsberg, Adam S.; Copp, Newton; Ulsh, Lisa; Drew, David E.

    2009-01-01

    A new interdisciplinary, introductory science course was offered for the first time during the 2007-2008 school year. The purpose of the course is to introduce students to the idea of working at the intersections of biology, chemistry, and physics and to recognize interconnections between the disciplines. Interdisciplinary laboratories are a key…

  6. Heme-nitrosyls: electronic structure implications for function in biology.

    PubMed

    Hunt, Andrew P; Lehnert, Nicolai

    2015-07-21

    The question of why mammalian systems use nitric oxide (NO), a potentially hazardous and toxic diatomic, as a signaling molecule to mediate important functions such as vasodilation (blood pressure control) and nerve signal transduction initially perplexed researchers when this discovery was made in the 1980s. Through extensive research over the past two decades, it is now well rationalized why NO is used in vivo for these signaling functions, and that heme proteins play a dominant role in NO signaling in mammals. Key insight into the properties of heme-nitrosyl complexes that make heme proteins so well poised to take full advantage of the unique properties of NO has come from in-depth structural, spectroscopic, and theoretical studies on ferrous and ferric heme-nitrosyls. This Account highlights recent findings that have led to greater understanding of the electronic structures of heme-nitrosyls, and the contributions that model complex studies have made to elucidate Fe-NO bonding are highlighted. These results are then discussed in the context of the biological functions of heme-nitrosyls, in particular in soluble guanylate cyclase (sGC; NO signaling), nitrophorins (NO transport), and NO-producing enzymes. Central to this Account is the thermodynamic σ-trans effect of NO, and how this relates to the activation of the universal mammalian NO sensor sGC, which uses a ferrous heme as the high affinity "NO detection unit". It is shown via detailed spectroscopic and computational studies that the strong and very covalent Fe(II)-NO σ-bond is at the heart of the strong thermodynamic σ-trans effect of NO, which greatly weakens the proximal Fe-NHis (or Fe-SCys) bond in six-coordinate ferrous heme-nitrosyls. In sGC, this causes the dissociation of the proximally bound histidine ligand upon NO binding to the ferrous heme, inducing a significant conformational change that activates the sGC catalytic domain for the production of cGMP. This, in turn, leads to vasodilation and

  7. Accelerating self-consistent field convergence with the augmented Roothaan–Hall energy function

    PubMed Central

    Hu, Xiangqian; Yang, Weitao

    2010-01-01

    Based on Pulay’s direct inversion iterative subspace (DIIS) approach, we present a method to accelerate self-consistent field (SCF) convergence. In this method, the quadratic augmented Roothaan–Hall (ARH) energy function, proposed recently by Høst and co-workers [J. Chem. Phys. 129, 124106 (2008)], is used as the object of minimization for obtaining the linear coefficients of Fock matrices within DIIS. This differs from the traditional DIIS of Pulay, which uses an object function derived from the commutator of the density and Fock matrices. Our results show that the present algorithm, abbreviated ADIIS, is more robust and efficient than the energy-DIIS (EDIIS) approach. In particular, several examples demonstrate that the combination of ADIIS and DIIS (“ADIIS+DIIS”) is highly reliable and efficient in accelerating SCF convergence. PMID:20136307

  8. Lung function, biological monitoring, and biological effect monitoring of gemstone cutters exposed to beryls

    PubMed Central

    Wegner, R.; Heinrich-Ramm, R.; Nowak, D.; Olma, K.; Poschadel, B.; Szadkowski, D.

    2000-01-01

    OBJECTIVES—Gemstone cutters are potentially exposed to various carcinogenic and fibrogenic metals such as chromium, nickel, aluminium, and beryllium, as well as to lead. Increased beryllium concentrations had been reported in the air of workplaces of beryl cutters in Idar-Oberstein, Germany. The aim of the survey was to study the excretion of beryllium in cutters and grinders with occupational exposure to beryls—for example, aquamarines and emeralds—to examine the prevalence of beryllium sensitisation with the beryllium lymphocyte transformation test (BeLT), to examine the prevalence of lung disease induced by beryllium, to describe the internal load of the respective metals relative to work process, and to screen for genotoxic effects in this particular profession.
METHODS—In a cross sectional investigation, 57 out of 100 gemstone cutters working in 12 factories in Idar-Oberstein with occupational exposure to beryls underwent medical examinations, a chest radiograph, lung function testing (spirometry, airway resistance with the interrupter technique), and biological monitoring, including measurements of aluminium, chromium, and nickel in urine as well as lead in blood. Beryllium in urine was measured with a newly developed direct electrothermal atomic absorption spectroscopy technique with a measurement limit of 0.06 µg/l. Also, cytogenetic tests (rates of micronuclei and sister chromatid exchange), and a BeLT were performed. Airborne concentrations of beryllium were measured in three factories. As no adequate local control group was available, the cutters were categorised into those with an exposure to beryls of >4 hours/week (group A) and ⩽4 hours/week (group B).
RESULTS—Clinical, radiological, or spirometric abnormalities indicating pneumoconiosis were detected in none of the gemstone cutters. Metal concentrations in biological material were far below the respective biological limit values, and beryllium in urine was only measurable in

  9. [Experimental studies of the relative biological effectiveness of accelerated charged particles varying in energy].

    PubMed

    Fedorenko, B S; Petrov, V M; Smirnova, O A; Vorozhtsova, S V; Abrosimova, A N

    2006-01-01

    Experimental results and literary data were analyzed for the relative biological effectiveness of heavy charged particles in a broad range of energy and LET to cells of humans and other mammals in culture, whole body of laboratory animals, microorganisms, bacteriophages, and plants. Analyzed were data obtained with the use of a diversity of tests of acute and delayed lesions induced by ionizing radiation, cancers and cataracts, specifically. Non-parametric methods are applied in parallel to the classic method of calculating the coefficients of relative biological effectiveness by correlating the equal-effective doses of the standard and a given radiation. Consideration is given to factors that may modify RBE values estimated for different types of radiation. PMID:17193971

  10. An accelerated framework for the classification of biological targets from solid-state micropore data.

    PubMed

    Hanif, Madiha; Hafeez, Abdul; Suleman, Yusuf; Mustafa Rafique, M; Butt, Ali R; Iqbal, Samir M

    2016-10-01

    Micro- and nanoscale systems have provided means to detect biological targets, such as DNA, proteins, and human cells, at ultrahigh sensitivity. However, these devices suffer from noise in the raw data, which continues to be significant as newer and devices that are more sensitive produce an increasing amount of data that needs to be analyzed. An important dimension that is often discounted in these systems is the ability to quickly process the measured data for an instant feedback. Realizing and developing algorithms for the accurate detection and classification of biological targets in realtime is vital. Toward this end, we describe a supervised machine-learning approach that records single cell events (pulses), computes useful pulse features, and classifies the future patterns into their respective types, such as cancerous/non-cancerous cells based on the training data. The approach detects cells with an accuracy of 70% from the raw data followed by an accurate classification when larger training sets are employed. The parallel implementation of the algorithm on graphics processing unit (GPU) demonstrates a speedup of three to four folds as compared to a serial implementation on an Intel Core i7 processor. This incredibly efficient GPU system is an effort to streamline the analysis of pulse data in an academic setting. This paper presents for the first time ever, a non-commercial technique using a GPU system for realtime analysis, paired with biological cluster targeting analysis. PMID:27480732

  11. Phytochrome from Green Plants: Properties and biological Function

    SciTech Connect

    Quail, Peter H.

    2014-07-25

    Pfr conformer reverses this activity upon initial light exposure, inducing the switch to photomorphogenic development. This reversal involves light-triggered translocation of the photoactivated phy molecule into the nucleus where it interacts with PIF-family members, inducing rapid phosphorylation and degradation of the PIFs via the ubiquitin-proteasome system. This degradation in turn elicits rapid alterations in gene expression that drive the deetiolation transition. This project has made considerable progress in defining phy-PIF signaling activity in controlling the SAR. The biological functions of the multiple PIF-family members in controlling the SAR, including dissection of the relative contributions of the individual PIFs to this process, as well as to diurnal growth-control oscillations, have been investigated using higher-order pif-mutant combinations. Using microarray analysis of a quadruple pif mutant we have defined the shade-induced, PIF-regulated transcriptional network genome-wide. This has revealed that a dynamic antagonism between the phys and PIFs generates selective reciprocal responses during deetiolation and the SAR in a rapidly light-responsive transcriptional network. Using integrated RNA-seq and ChIP-seq analysis of higher order pif-mutant combinations, we have defined the direct gene-targets of PIF transcriptional regulation, and have obtained evidence that this regulation involves differential direct targeting of rapidly light-responsive genes by the individual PIF-family members. This project has provided significant advances in our understanding of the molecular mechanisms by which the phy-PIF photosensory signaling pathway regulates an important bioenergy-related plant response to the light environment. The identification of molecular targets in the primary transcriptional-regulatory circuitry of this pathway has the potential to enable genetic or reverse-genetic manipulation of the partitioning of carbon between reproductive and

  12. Trajectories of Microbial Community Function in Response to Accelerated Remediation of Subsurface Metal Contaminants

    SciTech Connect

    Firestone, Mary

    2015-01-14

    Objectives of proposed research were to; Determine if the trajectories of microbial community composition and function following organic carbon amendment can be related to, and predicted by, key environmental determinants; Assess the relative importance of the characteristics of the indigenous microbial community, sediment, groundwater, and concentration of organic carbon amendment as the major determinants of microbial community functional response and bioremediation capacity; and Provide a fundamental understanding of the microbial community ecology underlying subsurface metal remediation requisite to successful application of accelerated remediation and long-term stewardship of DOE-IFC sites.

  13. Androgen induced acceleration of functional recovery after rat sciatic nerve injury.

    PubMed

    Brown, Todd J.; Khan, Talat; Jones, Kathryn J.

    1999-01-01

    PURPOSE: Testosterone (T) treatment accelerates recovery from facial paralysis after facial nerve crush in hamsters. In this study, we extended those studies to another injury model and asked the following question: Will T treatment accelerate recovery from lower limb paralysis following sciatic nerve crush in the rat? METHODS: Castrated adult male rats received a right side sciatic nerve crush at the level of the sciatic notch, with the left side serving as control. Half the animals received a subcutaneous implant of a propionated form of T (TP), the others were sham-implanted. Weekly testing using the Sciatic Functional Index (SFI), a quantitative measure of locomotion, was done for 7 weeks postoperative (wpo). RESULTS: Between 3 and 5 weeks post-op, the average SFI score of the TP-treated group was higher than controls. This difference was significant at 4 wpo, indicating an accelerated degree of functional recovery. At these timepoints, the differences were attributable to the footprint or paw length and associated with calf muscle reinnervation rather than the toespreading component associated with intrinsic foot muscle rein-nervation. Beyond 5 wpo, there were no differences in the SFI scores. CONCLUSION: The results indicate that, as with facial nerve regeneration in the hamster, testosterone accelerates functional recovery from hind limb paralysis following sciatic nerve injury in the rat. While the responses of spinal motoneurons to injury can differ from those of cranial motoneurons, in this case it appears that they share a similar response to the trophic actions of androgen. This is important in the context of designing therapeutic strategies for dealing with direct trauma to motoneurons resulting from both peripheral and central nervous system trauma, such as spinal cord injury. PMID:12671219

  14. Distribution of computer functionality for accelerator control at the Brookhaven AGS

    SciTech Connect

    Stevens, A.; Clifford, T.; Frankel, R.

    1985-01-01

    A set of physical and functional system components and their interconnection protocols have been established for all controls work at the AGS. Portions of these designs were tested as part of enhanced operation of the AGS as a source of polarized protons and additional segments will be implemented during the continuing construction efforts which are adding heavy ion capability to our facility. Included in our efforts are the following computer and control system elements: a broad band local area network, which embodies MODEMS; transmission systems and branch interface units; a hierarchical layer, which performs certain data base and watchdog/alarm functions; a group of work station processors (Apollo's) which perform the function of traditional minicomputer host(s) and a layer, which provides both real time control and standardization functions for accelerator devices and instrumentation. Data base and other accelerator functionality is assigned to the most correct level within our network for both real time performance, long-term utility, and orderly growth.

  15. Distribution of computer functionality for accelerator control at the Brookhaven AGS

    SciTech Connect

    Stevens, A.; Clifford, T.; Frankel, R.

    1985-10-01

    A set of physical and functional system components and their interconnection protocols have been established for all controls work at the AGS. Portions of these designs were tested as part of enhanced operation of the AGS as a source of polarized protons and additional segments will be implemented during the continuing construction efforts which are adding heavy ion capability to our facility. Included in our efforts are the following computer and control system elements: a broad band local area network, which embodies MODEMS; transmission systems and branch interface units; a hierarchical layer, which performs certain data base and watchdog/alarm functions; a group of work station processors (Apollo's) which perform the function of traditional minicomputer host(s) and a layer, which provides both real time control and standardization functions for accelerator devices and instrumentation. Data base and other accelerator functionality is assigned to the most correct level within our network for both real time performance, long-term utility, and orderly growth.

  16. Biological Manipulation of Migration Rate: The Use of Advanced Photoperiod to Accelerate Smoltification in Yearling Chinook Salmon, Annual Report 1989.

    SciTech Connect

    Giorgi, Albert E.; Muir, William D.; Zaugg, Waldo S.

    1991-01-01

    Research was conducted to assess the feasibility of biologically manipulating physiological development and migratory behavior of yearling spring chinook salmon, Oncorhynchus tshawytscha. At Dworshak National Fish Hatchery, treatment groups were exposed to a variety of advanced photoperiod cycles preceding release to accelerate smolt development. Physiological development and migratory performance were described for all groups. The treatments included a 14-week exposure to a 3-month advanced photoperiod cycle, an 18-week exposure to a 3-month advanced photoperiod cycle, and an 18-week exposure to a 4-month advanced photoperiod cycle. Two additional groups, an 18-week exposure to a 3-month advanced photoperiod and a control equivalent, were reared at an elevated water temperature (11{degrees}C) for 2 weeks prior to release. Results indicated that the treated fish which were the most physiologically advanced at release were detected in the highest proportion at collector dams and also migrated fastest downstream. 26 refs., 10 figs., 5 tabs.

  17. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  18. Correction of dispersion and the betatron functions in the CEBAF accelerator

    SciTech Connect

    Lebedev, V.A.; Bickley, M.; Schaffner, S.; Zeijts, J. van; Krafft, G.A.; Watson, C.

    1996-10-01

    During the commissioning of the CEBAF accelerator, correction of dispersion and momentum compaction, and, to a lesser extent, transverse transfer matrices were essential for robust operation. With changing machine conditions, repeated correction was found necessary. To speed the diagnostic process the authors developed a method which allows one to rapidly track the machine optics. The method is based on measuring the propagation of 30 Hz modulated betatron oscillations downstream of a point of perturbation. Compared to the usual methods of dispersion or difference orbit measurement, synchronous detection of the beam displacement, as measured by beam position monitors, offers significantly improved speed and accuracy of the measurements. The beam optics of the accelerator was altered to decrease lattice sensitivity at critical points and to simplify control of the betatron function match. The calculation of the Courant-Snyder invariant from signals of each pair of nearby beam position monitors has allowed one to perform on-line measurement and correction of the lattice properties.

  19. Discovery of biological networks from diverse functional genomic data

    PubMed Central

    Myers, Chad L; Robson, Drew; Wible, Adam; Hibbs, Matthew A; Chiriac, Camelia; Theesfeld, Chandra L; Dolinski, Kara; Troyanskaya, Olga G

    2005-01-01

    We have developed a general probabilistic system for query-based discovery of pathway-specific networks through integration of diverse genome-wide data. This framework was validated by accurately recovering known networks for 31 biological processes in Saccharomyces cerevisiae and experimentally verifying predictions for the process of chromosomal segregation. Our system, bioPIXIE, a public, comprehensive system for integration, analysis, and visualization of biological network predictions for S. cerevisiae, is freely accessible over the worldwide web. PMID:16420673

  20. Accelerator-Based Biological Irradiation Facility Simulating Neutron Exposure from an Improvised Nuclear Device.

    PubMed

    Xu, Yanping; Randers-Pehrson, Gerhard; Turner, Helen C; Marino, Stephen A; Geard, Charles R; Brenner, David J; Garty, Guy

    2015-10-01

    We describe here an accelerator-based neutron irradiation facility, intended to expose blood or small animals to neutron fields mimicking those from an improvised nuclear device at relevant distances from the epicenter. Neutrons are generated by a mixed proton/deuteron beam on a thick beryllium target, generating a broad spectrum of neutron energies that match those estimated for the Hiroshima bomb at 1.5 km from ground zero. This spectrum, dominated by neutron energies between 0.2 and 9 MeV, is significantly different from the standard reactor fission spectrum, as the initial bomb spectrum changes when the neutrons are transported through air. The neutron and gamma dose rates were measured using a custom tissue-equivalent gas ionization chamber and a compensated Geiger-Mueller dosimeter, respectively. Neutron spectra were evaluated by unfolding measurements using a proton-recoil proportional counter and a liquid scintillator detector. As an illustration of the potential use of this facility we present micronucleus yields in single divided, cytokinesis-blocked human peripheral lymphocytes up to 1.5 Gy demonstrating 3- to 5-fold enhancement over equivalent X-ray doses. This facility is currently in routine use, irradiating both mice and human blood samples for evaluation of neutron-specific biodosimetry assays. Future studies will focus on dose reconstruction in realistic mixed neutron/photon fields. PMID:26414507

  1. Accelerating the Discovery of Biologically Active Small Molecules Using a High-Throughput Yeast Halo Assay#

    PubMed Central

    Gassner, Nadine C.; Tamble, Craig M.; Bock, Jonathan E.; Cotton, Naomi; White, Kimberly N.; Tenney, Karen; St. Onge, Robert P.; Proctor, Michael J.; Giaever, Guri; Davis, Ronald W.; Crews, Phillip; Holman, Theodore R.; Lokey, R. Scott

    2008-01-01

    The budding yeast Saccharomyces cerevisiae, a powerful model system for the study of basic eukaryotic cell biology, has been used increasingly as a screening tool for the identification of bioactive small molecules. We have developed a novel yeast toxicity screen that is easily automated and compatible with high-throughput screening robotics. The new screen is quantitative and allows inhibitory potencies to be determined, since the diffusion of the sample provides a concentration gradient and a corresponding toxicity halo. The efficacy of this new screen was illustrated by testing materials including 3,104 compounds from the NCI libraries, 167 marine sponge crude extracts, and 149 crude marine-derived fungal extracts. There were 46 active compounds among the NCI set. One very active extract was selected for bioactivity-guided fractionation resulting in the identification of crambescidin 800 as a potent antifungal agent. PMID:17291044

  2. Leukocyte Telomere Length in Young Adults Born Preterm: Support for Accelerated Biological Ageing

    PubMed Central

    Smeets, Carolina C. J.; Codd, Veryan; Samani, Nilesh J.; Hokken-Koelega, Anita C. S.

    2015-01-01

    Background Subjects born preterm have an increased risk for age-associated diseases, such as cardiovascular disease in later life, but the underlying causes are largely unknown. Shorter leukocyte telomere length (LTL), a marker of biological age, is associated with increased risk of cardiovascular disease. Objectives To compare LTL between subjects born preterm and at term and to assess if LTL is associated with other putative cardiovascular risk factors at young adult age. Methods We measured mean LTL in 470 young adults. LTL was measured using a quantitative PCR assay and expressed as T/S ratio. We analyzed the influence of gestational age on LTL and compared LTL between subjects born preterm (n = 186) and at term (n = 284). Additionally, we analyzed the correlation between LTL and potential risk factors of cardiovascular disease. Results Gestational age was positively associated with LTL (r = 0.11, p = 0.02). Subjects born preterm had shorter LTL (mean (SD) T/S ratio = 3.12 (0.44)) than subjects born at term (mean (SD) T/S ratio = 3.25 (0.46)), p = 0.003). The difference remained significant after adjustment for gender and size at birth (p = 0.001). There was no association of LTL with any one of the putative risk factors analyzed. Conclusions Young adults born preterm have shorter LTL than young adults born at term. Although we found no correlation between LTL and risk for CVD at this young adult age, this biological ageing indicator may contribute to CVD and other adult onset diseases at a later age in those born preterm. PMID:26619005

  3. Biological soil crusts accelerate the nitrogen cycle through large NO and HONO emissions in drylands

    PubMed Central

    Wu, Dianming; Tamm, Alexandra; Ruckteschler, Nina; Rodríguez-Caballero, Emilio; Meusel, Hannah; Elbert, Wolfgang; Behrendt, Thomas; Sörgel, Matthias; Cheng, Yafang; Crutzen, Paul J.; Su, Hang; Pöschl, Ulrich

    2015-01-01

    Reactive nitrogen species have a strong influence on atmospheric chemistry and climate, tightly coupling the Earth’s nitrogen cycle with microbial activity in the biosphere. Their sources, however, are not well constrained, especially in dryland regions accounting for a major fraction of the global land surface. Here, we show that biological soil crusts (biocrusts) are emitters of nitric oxide (NO) and nitrous acid (HONO). Largest fluxes are obtained by dark cyanobacteria-dominated biocrusts, being ∼20 times higher than those of neighboring uncrusted soils. Based on laboratory, field, and satellite measurement data, we obtain a best estimate of ∼1.7 Tg per year for the global emission of reactive nitrogen from biocrusts (1.1 Tg a−1 of NO-N and 0.6 Tg a−1 of HONO-N), corresponding to ∼20% of global nitrogen oxide emissions from soils under natural vegetation. On continental scales, emissions are highest in Africa and South America and lowest in Europe. Our results suggest that dryland emissions of reactive nitrogen are largely driven by biocrusts rather than the underlying soil. They help to explain enigmatic discrepancies between measurement and modeling approaches of global reactive nitrogen emissions. As the emissions of biocrusts strongly depend on precipitation events, climate change affecting the distribution and frequency of precipitation may have a strong impact on terrestrial emissions of reactive nitrogen and related climate feedback effects. Because biocrusts also account for a large fraction of global terrestrial biological nitrogen fixation, their impacts should be further quantified and included in regional and global models of air chemistry, biogeochemistry, and climate. PMID:26621714

  4. Biological soil crusts accelerate the nitrogen cycle through large NO and HONO emissions in drylands.

    PubMed

    Weber, Bettina; Wu, Dianming; Tamm, Alexandra; Ruckteschler, Nina; Rodríguez-Caballero, Emilio; Steinkamp, Jörg; Meusel, Hannah; Elbert, Wolfgang; Behrendt, Thomas; Sörgel, Matthias; Cheng, Yafang; Crutzen, Paul J; Su, Hang; Pöschl, Ulrich

    2015-12-15

    Reactive nitrogen species have a strong influence on atmospheric chemistry and climate, tightly coupling the Earth's nitrogen cycle with microbial activity in the biosphere. Their sources, however, are not well constrained, especially in dryland regions accounting for a major fraction of the global land surface. Here, we show that biological soil crusts (biocrusts) are emitters of nitric oxide (NO) and nitrous acid (HONO). Largest fluxes are obtained by dark cyanobacteria-dominated biocrusts, being ∼20 times higher than those of neighboring uncrusted soils. Based on laboratory, field, and satellite measurement data, we obtain a best estimate of ∼1.7 Tg per year for the global emission of reactive nitrogen from biocrusts (1.1 Tg a(-1) of NO-N and 0.6 Tg a(-1) of HONO-N), corresponding to ∼20% of global nitrogen oxide emissions from soils under natural vegetation. On continental scales, emissions are highest in Africa and South America and lowest in Europe. Our results suggest that dryland emissions of reactive nitrogen are largely driven by biocrusts rather than the underlying soil. They help to explain enigmatic discrepancies between measurement and modeling approaches of global reactive nitrogen emissions. As the emissions of biocrusts strongly depend on precipitation events, climate change affecting the distribution and frequency of precipitation may have a strong impact on terrestrial emissions of reactive nitrogen and related climate feedback effects. Because biocrusts also account for a large fraction of global terrestrial biological nitrogen fixation, their impacts should be further quantified and included in regional and global models of air chemistry, biogeochemistry, and climate. PMID:26621714

  5. Relative biological effectiveness in canine osteosarcoma cells irradiated with accelerated charged particles

    PubMed Central

    Maeda, Junko; Cartwright, Ian M.; Haskins, Jeremy S.; Fujii, Yoshihiro; Fujisawa, Hiroshi; Hirakawa, Hirokazu; Uesaka, Mitsuru; Kitamura, Hisashi; Fujimori, Akira; Thamm, Douglas H.; Kato, Takamitsu A.

    2016-01-01

    Heavy ions, characterized by high linear energy transfer (LET) radiation, have advantages compared with low LET protons and photons in their biological effects. The application of heavy ions within veterinary clinics requires additional background information to determine heavy ion efficacy. In the present study, comparison of the cell-killing effects of photons, protons and heavy ions was investigated in canine osteosarcoma (OSA) cells in vitro. A total of four canine OSA cell lines with various radiosensitivities were irradiated with 137Cs gamma-rays, monoenergetic proton beams, 50 keV/µm carbon ion spread out Bragg peak beams and 200 keV/µm iron ion monoenergetic beams. Clonogenic survival was examined using colony-forming as says, and relative biological effectiveness (RBE) values were calculated relative to gamma-rays using the D10 value, which is determined as the dose (Gy) resulting in 10% survival. For proton irradiation, the RBE values for all four cell lines were 1.0–1.1. For all four cell lines, exposure to carbon ions yielded a decreased cell survival compared with gamma-rays, with the RBE values ranging from 1.56–2.10. Iron ions yielded the lowest cell survival among tested radiation types, with RBE values ranging from 3.51–3.69 observed in the three radioresistant cell lines. The radiosensitive cell line investigated demonstrated similar cell survival for carbon and iron ion irradiation. The results of the present study suggest that heavy ions are more effective for killing radioresistant canine OSA cells when compared with gamma-rays and protons. This markedly increased efficiency of cell killing is an attractive reason for utilizing heavy ions for radioresistant canine OSA. PMID:27446477

  6. Biological Effects of Particles with Very High Energy Deposition on Mammalian Cells Utilizing the Brookhaven Tandem Van de Graaff Accelerator

    NASA Technical Reports Server (NTRS)

    Saha, Janapriya; Cucinotta, Francis A.; Wang, Minli

    2013-01-01

    High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of high charge and energy (HZE) nuclei and secondary protons and neutrons, and secondaries from protons in SPE (Solar Particle Event) pose a major health risk to astronauts due to induction of DNA damage and oxidative stress. Experiments with high energy particles mimicking the space environment for estimation of radiation risk are being performed at NASA Space Radiation Laboratory at BNL. Experiments with low energy particles comparing to high energy particles of similar LET are of interest for investigation of the role of track structure on biological effects. For this purpose, we report results utilizing the Tandem Van de Graaff accelerator at BNL. The primary objective of our studies is to elucidate the influence of high vs low energy deposition on track structure, delta ray contribution and resulting biological responses. These low energy ions are of special relevance as these energies may occur following absorption through the spacecraft and shielding materials in human tissues and nuclear fragments produced in tissues by high energy protons and neutrons. This study will help to verify the efficiency of these low energy particles and better understand how various cell types respond to them.

  7. Spatio-temporal radiation biology with conventionally or laser-accelerated particles for ELIMED

    SciTech Connect

    Ristić-Fira, A.; Bulat, T.; Keta, O.; Petrović, I.; Romano, F.; Cirrone, P.; Cuttone, G.

    2013-07-26

    The aim of this study is to investigate the behavior of radio-resistant human malignant cells, thus enabling better understanding of radiobiological effects of ions in such a case. Radiation sources such as accelerated continuous ion beams and laser technology-based ultra short radiation sources with energy of around 10 MeV will be used. The HTB140 melanoma cells are chosen since it has been shown that they represent the limit case of cellular radio-resistance among the studied tumor cell lines. These cells are particularly interesting as they provide data on the very edge of inactivation capacity of each beam line that is tested. After exposing the cell monolayers to continuous radiations of low (γ-rays) and high (protons) linear energy transfer, the kinetics of disappearance of the phosphorylated histone H2AX (γ-H2AX) foci per cell will be determined. The same procedure will be performed with the pulsed high dose rate protons. Detection and quantification of γ-H2AX foci will be performed by immunohistochemical 3D time-dependent imaging analyses using laser scanning confocal microscopy. Immunoblotting will enable the follow-up of the relation between γ-H2AX and cell cycle arrest via the p53/p21 pathway. In such a way the spatio-temporal changes on sub-cellular level will be visualized, quantified and compared. These results will show whether there is a difference in the effects on cells between continuous and pulsed irradiation mode. Therefore, they will contribute to the data base that might promote pulsed sources for medical treatments of malignant growths.

  8. Spatio-temporal radiation biology with conventionally or laser-accelerated particles for ELIMED

    NASA Astrophysics Data System (ADS)

    Ristić-Fira, A.; Bulat, T.; Keta, O.; Romano, F.; Cirrone, P.; Cuttone, G.; Petrović, I.

    2013-07-01

    The aim of this study is to investigate the behavior of radio-resistant human malignant cells, thus enabling better understanding of radiobiological effects of ions in such a case. Radiation sources such as accelerated continuous ion beams and laser technology-based ultra short radiation sources with energy of around 10 MeV will be used. The HTB140 melanoma cells are chosen since it has been shown that they represent the limit case of cellular radio-resistance among the studied tumor cell lines. These cells are particularly interesting as they provide data on the very edge of inactivation capacity of each beam line that is tested. After exposing the cell monolayers to continuous radiations of low (γ-rays) and high (protons) linear energy transfer, the kinetics of disappearance of the phosphorylated histone H2AX (γ-H2AX) foci per cell will be determined. The same procedure will be performed with the pulsed high dose rate protons. Detection and quantification of γ-H2AX foci will be performed by immunohistochemical 3D time-dependent imaging analyses using laser scanning confocal microscopy. Immunoblotting will enable the follow-up of the relation between γ-H2AX and cell cycle arrest via the p53/p21 pathway. In such a way the spatio-temporal changes on sub-cellular level will be visualized, quantified and compared. These results will show whether there is a difference in the effects on cells between continuous and pulsed irradiation mode. Therefore, they will contribute to the data base that might promote pulsed sources for medical treatments of malignant growths.

  9. Harmonic oscillators: the quantization of simple systems in the old quantum theory and their functional roles in biology.

    PubMed

    Steele, Richard H

    2008-03-01

    This article introduces quantum physics into biology in an intuitive and non-intimidating manner. It extends the quantum aspects of harmonic oscillators, and electromagnetic fields, to their functional roles in biology. Central to this process are the De Broglie wave-particle duality equation, and the adiabatic invariant parameters, magnetic moment, angular momentum and magnetic flux, determined by Ehrenfest as imposing quantum constraints on the dynamics of charges in motion. In mechanisms designed to explain the generation of low-level light emissions in biology we have adopted a biological analog of the electrical circuitry modeled on the parallel plated capacitor, traversed by helical protein structures, capable of generating electromagnetic radiation in the optical spectral region. The charge carrier required for the emissions is an accelerating electron driven, in a cyclotron-type mechanism, by ATP-induced reverse electron transfer with the radial, emission, components, mediated by coulombic forces within the helical configurations. Adenine, an essential nucleotide constituent of DNA, was examined with its long wavelength absorption maximum determining the energetic parameters for the calculations. The calculations were made for a virtual 5-turn helix where each turn of the helix emits a different frequency, generating a biological quantum series. The components of six adiabatic invariant equations were found to be embedded in Planck's constant rendering them discrete, finite, non-random, non-statistical-Planck's constant precludes probability. A mechanism for drug-induced hallucination is described that might provide insights as to the possible role of electromagnetic fields in consciousness. Sodium acceleration through a proposed nerve membrane helical channel generated electromagnetic emissions in the microwave region in confirmation of reported microwave emission for active nerves and may explain saltatory nerve conduction. Theoretical calculations for a

  10. The IWOP Technique and Wigner-Function Approach to Quantum Effect of Mesoscopic Biological Cell

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Xia

    2014-09-01

    Using the IWOP technique, Wigner function theory and TFD theory, the quantization of a mesoscopic biological cell equivalent circuit is proposed, The quantum fluctuations of the mesoscopic biological cell are researched in thermal vacuum state and vacuum state. It is shown that the IWOP technique, Wigner function theory and Umezawa-Takahashi's TFD theory play the key role in quantizing a mesoscopic biological cell at finite temperature and the fluctuations and uncertainty increase with increasing temperature and decrease with prolonged time.

  11. Origins of Highly Structured Distribution Functions in Magnetic Reconnection Exhausts: Understanding Electron Acceleration and Heating

    NASA Astrophysics Data System (ADS)

    Shuster, J. R.; Wang, S.; Chen, L. J.; Bessho, N.; Guo, R.; Torbert, R. B.; Daughton, W. S.

    2014-12-01

    Electron velocity distribution functions (VDFs) during reconnection with negligible guide field from particle in cell (PIC) simulations and Cluster observations are studied to further understand electron acceleration and heating. Until recently, electrons in the exhaust of reconnection with negligible guide field were thought to be isotropic. PIC simulation results with zero guide field reveal that near the time of peak reconnection, VDFs become highly structured in magnetic islands and open exhausts. Ring, arc, and counterstreaming populations are generic and lasting constituents of exhaust electron VDFs. Analyses of particle trajectories indicate that a number of mechanisms including Fermi acceleration, the parallel potential, and adiabatic heating contribute to the energization of exhaust electrons. Near the electron diffusion region (EDR), exhaust electrons exhibit large Te⊥ due to ring and arc populations of electrons accelerated in the EDR. Farther away from the EDR, the VDFs show a mixture of electrons from the EDR and those crossing the separatrix from the inflow. Pitch angle scattering is effective near the exhaust midplane, away from the EDR and before reaching the magnetic pileup region, producing isotropic, high-energy electrons, while the low energy exhaust electrons exhibit the anisotropy Te// > Te⊥ characteristic of the inflow. The work done on the electrons by the perpendicular electric field between the end of EDR and the magnetic pileup region is due to Fermi acceleration which leads to a net increase in the electron's parallel velocity. For the net increase of electrons' v⊥ beyond the EDR, pitch angle scattering effectively converts v// gained by acceleration from the parallel potential into v⊥. Electron's v⊥ further increases downstream through adiabatic heating from the increasing magnetic field in addition to less efficient pitch angle scattering. The parallel potential and the magnetic bottle together determine the trapped

  12. k-t FASTER: Acceleration of functional MRI data acquisition using low rank constraints

    PubMed Central

    Chiew, Mark; Smith, Stephen M; Koopmans, Peter J; Graedel, Nadine N; Blumensath, Thomas; Miller, Karla L

    2015-01-01

    Purpose In functional MRI (fMRI), faster sampling of data can provide richer temporal information and increase temporal degrees of freedom. However, acceleration is generally performed on a volume-by-volume basis, without consideration of the intrinsic spatio-temporal data structure. We present a novel method for accelerating fMRI data acquisition, k-t FASTER (FMRI Accelerated in Space-time via Truncation of Effective Rank), which exploits the low-rank structure of fMRI data. Theory and Methods Using matrix completion, 4.27× retrospectively and prospectively under-sampled data were reconstructed (coil-independently) using an iterative nonlinear algorithm, and compared with several different reconstruction strategies. Matrix reconstruction error was evaluated; a dual regression analysis was performed to determine fidelity of recovered fMRI resting state networks (RSNs). Results The retrospective sampling data showed that k-t FASTER produced the lowest error, approximately 3–4%, and the highest quality RSNs. These results were validated in prospectively under-sampled experiments, with k-t FASTER producing better identification of RSNs than fully sampled acquisitions of the same duration. Conclusion With k-t FASTER, incoherently under-sampled fMRI data can be robustly recovered using only rank constraints. This technique can be used to improve the speed of fMRI sampling, particularly for multivariate analyses such as temporal independent component analysis. Magn Reson Med 74:353–364, 2015. © 2014 Wiley Periodicals, Inc. PMID:25168207

  13. Ground Test of the Urine Processing Assembly for Accelerations and Transfer Functions

    NASA Technical Reports Server (NTRS)

    Houston, Janice; Almond, Deborah F. (Technical Monitor)

    2001-01-01

    This viewgraph presentation gives an overview of the ground test of the urine processing assembly for accelerations and transfer functions. Details are given on the test setup, test data, data analysis, analytical results, and microgravity assessment. The conclusions of the tests include the following: (1) the single input/multiple output method is useful if the data is acquired by tri-axial accelerometers and inputs can be considered uncorrelated; (2) tying coherence with the matrix yields higher confidence in results; (3) the WRS#2 rack ORUs need to be isolated; (4) and future work includes a plan for characterizing performance of isolation materials.

  14. GPU Accelerated Implementation of Density Functional Theory for Hybrid QM/MM Simulations.

    PubMed

    Nitsche, Matías A; Ferreria, Manuel; Mocskos, Esteban E; González Lebrero, Mariano C

    2014-03-11

    The hybrid simulation tools (QM/MM) evolved into a fundamental methodology for studying chemical reactivity in complex environments. This paper presents an implementation of electronic structure calculations based on density functional theory. This development is optimized for performing hybrid molecular dynamics simulations by making use of graphic processors (GPU) for the most computationally demanding parts (exchange-correlation terms). The proposed implementation is able to take advantage of modern GPUs achieving acceleration in relevant portions between 20 to 30 times faster than the CPU version. The presented code was extensively tested, both in terms of numerical quality and performance over systems of different size and composition. PMID:26580175

  15. Oxidative metabolites of lycopene and their biological functions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To gain a better understanding of the beneficial biological activities of lycopene on cancer prevention, a greater knowledge of the metabolism of lycopene is needed. In particular, the identification of lycopene metabolites and oxidation products in vivo; the importance of tissue specific lycopene c...

  16. [Biological functions and the practical use of chitin].

    PubMed

    Feofilova, E P

    1984-01-01

    The review is dedicated to chitin--a wide-spread in nature polyaminosaccharide. Its main physico-chemical properties and biological role in the cell are analyzed. The review centres round the practical use of chitin and its derivatives. Natural resources, modern modes for production and application of chitin and its derivatives in industry, medicine, biotechnology and agriculture are discussed. PMID:6371781

  17. Cerenkov Radiation: A Multi-functional Approach for Biological Sciences

    NASA Astrophysics Data System (ADS)

    Ma, Xiaowei; Wang, Jing; Cheng, Zhen

    2014-02-01

    Cerenkov radiation (CR) has been used in various biological research fields, which has aroused lots of attention in recent years. Combining optical imaging instruments and most of nuclear medicine imaging or radiotherapy probes, the CR was developed as a new imaging modality for biology studies, called Cerenkov luminescence imaging (CLI). On the other hand, it was novelly used as an internal excitation source to activate some fluorophores for energy transfer imaging. However, it also has some shortages such as relatively weak luminescence intensity and low penetration in tissue. Thus some scientific groups demonstrated to optimize the CLI and demonstrated it to three-dimension tomography. In this article, we elaborate on its principle, history, and applications and discuss a number of directions for technical improvements. Then concluded some advantages and shortages of CR and discuss some prospects of it.

  18. Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers

    PubMed Central

    Siegwart, Daniel J.; Leiendecker, Matthias; Langer, Robert; Anderson, Daniel G.

    2013-01-01

    Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized polymers without the need of an inert gas. Using ARGET ATRP, polymerization conditions were rapidly identified for eight different monomers, including the first ARGET ATRP of 2-(diethylamino)ethyl methacrylate and di(ethylene glycol) methyl ether methacrylate. In addition, butyl acrylate, oligo(ethylene glycol) methacrylate 300 and 475, 2-(dimethylamino)ethyl methacrylate, styrene, and methyl methacrylate were polymerized using bis(2-hydroxyethyl) disulfide bis(2-bromo-2-methylpropionate) as the initiator, tris(2-pyridylmethyl)amine as the ligand, and tin(II) 2-ethylhexanoate as the reducing agent. The catalyst and reducing agent concentration was optimized specifically for each monomer, and then a library of polymers was synthesized systematically using the optimized conditions. The disulfide-functionalized chains could be cleaved to two thiol-terminated chains upon exposure to dithiothreitol, which may have utility for the synthesis of polymer bioconjugates. Finally, we demonstrated that these new conditions translated perfectly to conventional batch polymerization. We believe the methods developed here may prove generally useful to accelerate the systematic optimization of a variety of chemical reactions and polymerizations. PMID:23599541

  19. Tables of phase functions, opacities, albedos, equilibrium temperatures, and radiative accelerations of dust grains in exoplanets

    NASA Astrophysics Data System (ADS)

    Budaj, J.; Kocifaj, M.; Salmeron, R.; Hubeny, I.

    2015-11-01

    There has been growing observational evidence for the presence of condensates in the atmospheres and/or comet-like tails of extrasolar planets. As a result, systematic and homogeneous tables of dust properties are useful in order to facilitate further observational and theoretical studies. In this paper we present calculations and analysis of non-isotropic phase functions, asymmetry parameter (mean cosine of the scattering angle), absorption and scattering opacities, single scattering albedos, equilibrium temperatures, and radiative accelerations of dust grains relevant for extrasolar planets. Our assumptions include spherical grain shape, Deirmendjian particle size distribution, and Mie theory. We consider several species: corundum/alumina, perovskite, olivines with 0 and 50 per cent iron content, pyroxenes with 0, 20, and 60 per cent iron content, pure iron, carbon at two different temperatures, water ice, liquid water, and ammonia. The presented tables cover the wavelength range of 0.2-500 μm and modal particle radii from 0.01 to 100 μm. Equilibrium temperatures and radiative accelerations assume irradiation by a non-blackbody source of light with temperatures from 7000 to 700 K seen at solid angles from 2π to 10-6 sr. The tables are provided to the community together with a simple code which allows for an optional, finite, angular dimension of the source of light (star) in the phase function.

  20. Accelerating the two-point and three-point galaxy correlation functions using Fourier transforms

    NASA Astrophysics Data System (ADS)

    Slepian, Zachary; Eisenstein, Daniel J.

    2016-01-01

    Though Fourier transforms (FTs) are a common technique for finding correlation functions, they are not typically used in computations of the anisotropy of the two-point correlation function (2PCF) about the line of sight in wide-angle surveys because the line-of-sight direction is not constant on the Cartesian grid. Here we show how FTs can be used to compute the multipole moments of the anisotropic 2PCF. We also show how FTs can be used to accelerate the 3PCF algorithm of Slepian & Eisenstein. In both cases, these FT methods allow one to avoid the computational cost of pair counting, which scales as the square of the number density of objects in the survey. With the upcoming large data sets of Dark Energy Spectroscopic Instrument, Euclid, and Large Synoptic Survey Telescope, FT techniques will therefore offer an important complement to simple pair or triplet counts.

  1. Two-axis acceleration of functional connectivity magnetic resonance imaging by parallel excitation of phase-tagged slices and half k-space acceleration.

    PubMed

    Jesmanowicz, Andrzej; Nencka, Andrew S; Li, Shi-Jiang; Hyde, James S

    2011-01-01

    Whole brain functional connectivity magnetic resonance imaging requires acquisition of a time course of gradient-recalled (GR) volumetric images. A method is developed to accelerate this acquisition using GR echo-planar imaging and radio frequency (RF) slice phase tagging. For N-fold acceleration, a tailored RF pulse excites N slices using a uniform-field transmit coil. This pulse is the Fourier transform of the profile for the N slices with a predetermined RF phase tag on each slice. A multichannel RF receive coil is used for detection. For n slices, there are n/N groups of slices. Signal-averaged reference images are created for each slice within each slice group for each member of the coil array and used to separate overlapping images that are simultaneously received. The time-overhead for collection of reference images is small relative to the acquisition time of a complete volumetric time course. A least-squares singular value decomposition method allows image separation on a pixel-by-pixel basis. Twofold slice acceleration is demonstrated using an eight-channel RF receive coil, with application to resting-state functional magnetic resonance imaging in the human brain. Data from six subjects at 3 T are reported. The method has been extended to half k-space acquisition, which not only provides additional acceleration, but also facilitates slice separation because of increased signal intensity of the central lines of k-space coupled with reduced susceptibility effects. PMID:22432957

  2. Association of occupational pesticide exposure with accelerated longitudinal decline in lung function.

    PubMed

    de Jong, Kim; Boezen, H Marike; Kromhout, Hans; Vermeulen, Roel; Postma, Dirkje S; Vonk, Judith M

    2014-06-01

    Cross-sectional studies have shown that occupational exposure to vapors, gases, dusts, and fumes (VGDF) and pesticides is associated with a lower level of lung function. These associations seem to be stronger in ever smokers. In the current study, we aimed to assess whether occupational exposure to VGDF and pesticides is associated with longitudinal decline in lung function. We used 12,772 observations from 2,527 participants in the Vlagtwedde-Vlaardingen Study, a general-population-based cohort study that followed subjects for 25 years, from 1965 to the last survey in 1989/1990. Job-specific exposure was estimated with the ALOHA+ job exposure matrix. Associations between exposures and annual changes in forced expiratory volume in 1 second (FEV1) and FEV1 as a percentage of inspiratory vital capacity (FEV1%VC) were assessed with linear mixed-effect models including sex, age, and level of lung function at the first measurement and pack-years of smoking at the last measurement. We tested for interaction between smoking and occupational exposure and assessed associations separately for never smokers and ever smokers. Exposure to VGDF was not associated with accelerated lung function decline after adjustment for co-exposure to pesticides. Exposure to pesticides, both in the last-held job and as a cumulative measure, was associated with accelerated decline in FEV1 and FEV1%VC, especially among ever smokers, where we found an excess change in FEV1 of -6.9 mL/year (95% confidence interval: -10.2, -3.7) associated with high pesticide exposure. PMID:24780843

  3. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

    PubMed

    Li, Jun; Zhao, Patrick X

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/. PMID:27446133

  4. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach

    PubMed Central

    Li, Jun; Zhao, Patrick X.

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/. PMID:27446133

  5. Muscle mass, structural and functional investigations of senescence-accelerated mouse P8 (SAMP8)

    PubMed Central

    Guo, An Yun; Leung, Kwok Sui; Siu, Parco Ming Fai; Qin, Jiang Hui; Chow, Simon Kwoon Ho; Qin, Ling; Li, Chi Yu; Cheung, Wing Hoi

    2015-01-01

    Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no report on the details such as sarcopenia onset time. Therefore, this study was to investigate the change of muscle mass, structure and functions during the development of sarcopenia. Besides the average life span, muscle mass, structural and functional measurements were also studied. Male SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and tested for ex vivo contractile properties and fatigability while the contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset of contractility decline was observed from month 8. Compared with month 8, most of the functional parameters at month 10 decreased significantly. Structurally, muscle fiber type IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is confirmed that SAMP8 mouse can be used in sarcopenia research with established time line in this study. PMID:26193895

  6. Characterization of a Source Importance Function in an Accelerator-Driven System

    SciTech Connect

    Kim, Yonghee; Park, Won Seok; Park, Chang Kue

    2003-07-15

    An importance function of the external spallation neutrons in an accelerator-driven system (ADS) has been introduced and characterized to address the source multiplication in a subcritical blanket. For a model ADS problem with a central external source, the source importance function is evaluated with a neutron transport code system. For a homogeneous core, essential characteristics of the importance are identified from the viewpoint of spatial distributions and energy dependency, etc. The importance function is evaluated for two different beam tube diameters, and its dependency on the buffer thickness is also addressed. In order to assess the impact of the power distribution on the importance function, a heterogeneous core is considered, and its importance function is evaluated. The analyses show that the peak importance occurs in the inner fuel blanket zone, not in the central source region, and the neutron importance in a high-energy regime, above 7 to 20 MeV, is high and increases with the energy. Also, the effects of a neutron absorber on the source importance are studied, and it is found that the source importance could be drastically reduced by surrounding the source with a strong neutron absorber such as B{sub 4}C. In addition, the source importance function is compared with the conventional {lambda}-mode adjoint flux, which is used as an importance function of fission neutrons in critical reactors. The comparison reveals that the inhomogeneous source importance function could be quite similar to the homogeneous {lambda}-mode adjoint flux in both spatial and spectral distributions for a wide range of subcriticality.

  7. Polymer gel dosimetry for neutron beam in the Neutron Exposure Accelerator System for Biological Effect Experiments (NASBEE)

    NASA Astrophysics Data System (ADS)

    Kawamura, H.; Sato, H.; Hamano, T.; Suda, M.; Yoshii, H.

    2015-01-01

    This study aimed to investigate whether gel dosimetry could be used to measure neutron beams. We irradiated a BANG3-type polymer gel dosimeter using neutron beams in the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) at the National Institute of Radiological Sciences (NIRS) in Japan. First, the polymer gels were irradiated from 0 to 7.0 Gy to investigate the dose-R2 responses. Irradiated gels were evaluated using 1.5-T magnetic resonance R2 images. Second, the polymer gels were irradiated to 1.0, 3.0, and 5.0 Gy to acquire a depth-R2 response curve. The dose-R2 response curve was linear up to approximately 7 Gy, with a slope of 1.25 Gy-1·s-1. Additionally, compared with the photon- irradiated gels, the neutron-irradiated gels had lower R2 values. The acquired depth-R2 curves of the central axis from the 3.0- and 5.0-Gy neutron dose-irradiated gels exhibited an initial build-up. Although, a detailed investigation is needed, polymer gel dosimetry is effective for measuring the dose-related R2 linearity and depth-R2 relationships of neutron beams.

  8. Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing

    PubMed Central

    McGuinness, Dagmara; Leierer, Johannes; Shapter, Olivier; Mohammed, Suhaib; Gingell-Littlejohn, Marc; Kingsmore, David B.; Little, Ann-Margaret; Kerschbaum, Julia; Schneeberger, Stefan; Maglione, Manuel; Nadalin, Silvio; Wagner, Sylvia; Königsrainer, Alfred; Aitken, Emma; Whalen, Henry; Clancy, Marc; McConnachie, Alex; Koppelstaetter, Christian; Stevenson, Karen S.; Shiels, Paul G.

    2016-01-01

    Introduction Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications. Methodology The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts. Results Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation. Conclusion These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia. PMID:26734715

  9. Unexpected functional similarities between gatekeeper tumour suppressor genes and proto-oncogenes revealed by systems biology.

    PubMed

    Zhao, Yongzhong; Epstein, Richard J

    2011-05-01

    Familial tumor suppressor genes comprise two subgroups: caretaker genes (CTs) that repair DNA, and gatekeeper genes (GKs) that trigger cell death. Since GKs may also induce cell cycle delay and thus enhance cell survival by facilitating DNA repair, we hypothesized that the prosurvival phenotype of GKs could be selected during cancer progression, and we used a multivariable systems biology approach to test this. We performed multidimensional data analysis, non-negative matrix factorization and logistic regression to compare the features of GKs with those of their putative antagonists, the proto-oncogenes (POs), as well as with control groups of CTs and functionally unrelated congenital heart disease genes (HDs). GKs and POs closely resemble each other, but not CTs or HDs, in terms of gene structure (P<0.001), expression level and breadth (P<0.01), DNA methylation signature (P<0.001) and evolutionary rate (P<0.001). The similar selection pressures and epigenetic trajectories of GKs and POs so implied suggest a common functional attribute that is strongly negatively selected-that is, a shared phenotype that enhances cell survival. The counterintuitive finding of similar evolutionary pressures affecting GKs and POs raises an intriguing possibility: namely, that cancer microevolution is accelerated by an epistatic cascade in which upstream suppressor gene defects subvert the normal bifunctionality of wild-type GKs by constitutively shifting the phenotype away from apoptosis towards survival. If correct, this interpretation would explain the hitherto unexplained phenomenon of frequent wild-type GK (for example, p53) overexpression in tumors. PMID:21368766

  10. Non-coding RNAs: Classification, Biology and Functioning.

    PubMed

    Hombach, Sonja; Kretz, Markus

    2016-01-01

    One of the long-standing principles of molecular biology is that DNA acts as a template for transcription of messenger RNAs, which serve as blueprints for protein translation. A rapidly growing number of exceptions to this rule have been reported over the past decades: they include long known classes of RNAs involved in translation such as transfer RNAs and ribosomal RNAs, small nuclear RNAs involved in splicing events, and small nucleolar RNAs mainly involved in the modification of other small RNAs, such as ribosomal RNAs and transfer RNAs. More recently, several classes of short regulatory non-coding RNAs, including piwi-associated RNAs, endogenous short-interfering RNAs and microRNAs have been discovered in mammals, which act as key regulators of gene expression in many different cellular pathways and systems. Additionally, the human genome encodes several thousand long non-protein coding RNAs >200 nucleotides in length, some of which play crucial roles in a variety of biological processes such as epigenetic control of chromatin, promoter-specific gene regulation, mRNA stability, X-chromosome inactivation and imprinting. In this chapter, we will introduce several classes of short and long non-coding RNAs, describe their diverse roles in mammalian gene regulation and give examples for known modes of action. PMID:27573892

  11. Water as a green solvent for efficient synthesis of isocoumarins through microwave-accelerated and Rh/Cu-catalyzed C-H/O-H bond functionalization

    SciTech Connect

    Li, Qiu; Yan, Yunnan; Wang, Xiaowei; Gong, Binwei; Tang, Xiaobo; Shi, JingJing; Xu, H. Eric; Yi, Wei

    2014-08-14

    Green chemistry that uses water as a solvent has recently received great attention in organic synthesis. Here we report an efficient synthesis of biologically important isocoumarins through direct cleavage of C–H/O–H bonds by microwave-accelerated and Rh/Cu-catalyzed oxidative annulation of various substituted benzoic acids, where water is used as the only solvent in the reactions. The remarkable features of this “green” methodology include high product yields, wide tolerance of various functional groups as substrates, and excellent region-/site-specificities, thus rendering this methodology a highly versatile and eco-friendly alternative to the existing methods for synthesizing isocoumarins and other biologically important derivatives such as isoquinolones.

  12. [Biological problems of origin and development of various physiological functions (theory and application)].

    PubMed

    Ivanov, K P

    2001-01-01

    The author presents some idea about origin and development of some physiological functions: outer breathing, breath function of blood, blood circulation, thermoregulation, energy supply. The conclusions about main directions of evolution of these functions and duration of their development in phylogeny were drawn. The author gave some examples of abrupt changes of development of these functions in different groups of animals and discussed possible reasons of such changes. General quantitative estimation of the results of evolution of these functions from the position of their summArized efficiency was done. Quantitative characteristics of optimization and efficiency limits of physiological functions were suggested on the base of new data in general biology and comparative physiology. The author put toward the hypothesis about conventional "mistakes" of evolution and showed deep biological reasons of some seriOus illness. The examples of some applied problems in biology, physiology and medicine that can be solved with the data on evolution of physiological functions are presented. PMID:11548400

  13. KEK digital accelerator

    NASA Astrophysics Data System (ADS)

    Iwashita, T.; Adachi, T.; Takayama, K.; Leo, K. W.; Arai, T.; Arakida, Y.; Hashimoto, M.; Kadokura, E.; Kawai, M.; Kawakubo, T.; Kubo, Tomio; Koyama, K.; Nakanishi, H.; Okazaki, K.; Okamura, K.; Someya, H.; Takagi, A.; Tokuchi, A.; Wake, M.

    2011-07-01

    The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA) is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR) ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  14. Commissioning of helium injector for coupled radio frequency quadrupole and separated function radio frequency quadrupole accelerator

    SciTech Connect

    Peng, Shixiang Chen, Jia; Ren, Haitao; Zhao, Jie; Xu, Yuan; Zhang, Tao; Xia, Wenlong; Gao, Shuli; Wang, Zhi; Luo, Yuting; Guo, Zhiyu; Zhang, Ailing; Chen, Jia'er; University of Chinese Academy of Sciences, Beijing 100049

    2014-02-15

    A project to study a new type of acceleration structure has been launched at Peking University, in which a traditional radio frequency quadrupole (RFQ) and a separated function radio frequency quadrupole are coupled in one cavity to accelerate the He+ beam. A helium injector for this project is developed. The injector consists of a 2.45 GHz permanent magnet electron cyclotron resonance ion source and a 1.16 m long low energy beam transport (LEBT). The commissioning of this injector was carried out and an onsite test was held in June 2013. A 14 mA He+ beam with the energy of 30 keV has been delivered to the end of the LEBT, where a diaphragm with the diameter of 7 mm is located. The position of the diaphragm corresponds to the entrance of the RFQ electrodes. The beam emittance and fraction were measured after the 7 mm diaphragm. Its rms emittance is about 0.14 π mm mrad and the fraction of He+ is about 99%.

  15. Study of electron acceleration and x-ray radiation as a function of plasma density in capillary-guided laser wakefield accelerators

    SciTech Connect

    Ju, J.; Döpp, A.; Cros, B.; Svensson, K.; Genoud, G.; Wojda, F.; Burza, M.; Persson, A.; Lundh, O.; Wahlström, C.-G.; Ferrari, H.

    2013-08-15

    Laser wakefield electron acceleration in the blow-out regime and the associated betatron X-ray radiation were investigated experimentally as a function of the plasma density in a configuration where the laser is guided. Dielectric capillary tubes were employed to assist the laser keeping self-focused over a long distance by collecting the laser energy around its central focal spot. With a 40 fs, 16 TW pulsed laser, electron bunches with tens of pC charge were measured to be accelerated to an energy up to 300 MeV, accompanied by X-ray emission with a peak brightness of the order of 10{sup 21} ph/s/mm{sup 2}/mrad{sup 2}/0.1%BW. Electron trapping and acceleration were studied using the emitted X-ray beam distribution to map the acceleration process; the number of betatron oscillations performed by the electrons was inferred from the correlation between measured X-ray fluence and beam charge. A study of the stability of electron and X-ray generation suggests that the fluctuation of X-ray emission can be reduced by stabilizing the beam charge. The experimental results are in good agreement with 3D particle-in-cell (PIC) simulation.

  16. Chemically-functionalized microcantilevers for detection of chemical, biological and explosive material

    DOEpatents

    Pinnaduwage, Lal A [Knoxville, TN; Thundat, Thomas G [Knoxville, TN; Brown, Gilbert M [Knoxville, TN; Hawk, John Eric [Olive Branch, MS; Boiadjiev, Vassil I [Knoxville, TN

    2007-04-24

    A chemically functionalized cantilever system has a cantilever coated on one side thereof with a reagent or biological species which binds to an analyte. The system is of particular value when the analyte is a toxic chemical biological warfare agent or an explosive.

  17. Beyond iron: non-classical biological functions of bacterial siderophores.

    PubMed

    Johnstone, Timothy C; Nolan, Elizabeth M

    2015-04-14

    Bacteria secrete small molecules known as siderophores to acquire iron from their surroundings. For over 60 years, investigations into the bioinorganic chemistry of these molecules, including fundamental coordination chemistry studies, have provided insight into the crucial role that siderophores play in bacterial iron homeostasis. The importance of understanding the fundamental chemistry underlying bacterial life has been highlighted evermore in recent years because of the emergence of antibiotic-resistant bacteria and the need to prevent the global rise of these superbugs. Increasing reports of siderophores functioning in capacities other than iron transport have appeared recently, but reports of "non-classical" siderophore functions have long paralleled those of iron transport. One particular non-classical function of these iron chelators, namely antibiotic activity, was documented before the role of siderophores in iron transport was established. In this Perspective, we present an exposition of past and current work into non-classical functions of siderophores and highlight the directions in which we anticipate that this research is headed. Examples include the ability of siderophores to function as zincophores, chalkophores, and metallophores for a variety of other metals, sequester heavy metal toxins, transport boron, act as signalling molecules, regulate oxidative stress, and provide antibacterial activity. PMID:25764171

  18. Beyond Iron: Non-Classical Biological Functions of Bacterial Siderophores

    PubMed Central

    Johnstone, Timothy C.; Nolan, Elizabeth M.

    2015-01-01

    Bacteria secrete small molecules known as siderophores to acquire iron from their surroundings. For over 60 years, investigations into the bioinorganic chemistry of these molecules, including fundamental coordination chemistry studies, have provided insight into the crucial role that siderophores play in bacterial iron homeostasis. The importance of understanding the fundamental chemistry underlying bacterial life has been highlighted evermore in recent years because of the emergence of antibiotic-resistant bacteria and the need to prevent the global rise of these superbugs. Increasing reports of siderophores functioning in capacities other than iron transport have appeared recently, but reports of “non-classical” siderophore functions have long paralleled those of iron transport. One particular non-classical function of these iron chelators, namely antibiotic activity, was even documented before the role of siderophores in iron transport was established. In this Perspective, we present an exposition of past and current work into non-classical functions of siderophores and highlight the directions in which we anticipate that this research is headed. Examples include the ability of siderophores to function as zincophores, chalkophores, and metallophores for a variety of other metals, sequester heavy metal toxins, transport boron, act as signalling molecules, regulate oxidative stress, and provide antibacterial activity. PMID:25764171

  19. Engineering functional nanostructures for materials and biological applications

    NASA Astrophysics Data System (ADS)

    Subramani, Chandramouleeswaran

    Engineering nanostructures with complete control over the shape, composition, organization of the surface structures, and function remains a major challenge. In my work, I have fabricated nanostructures using functional polymer motifs and nanoparticles (NPs) via supramolecular and non-supramolecular interactions. In one of the approaches to generate nanostructures, I have integrated top-down approaches such as nanoimprint lithography, electron-beam lithography, and photolithography with the self-assembly (bottom-up) of NPs to provide nanostructures with tailored shape and function. In this strategy, I have developed a geometrically assisted orthogonal assembly of nanoparticles onto polymer features at precisely defined locations. This versatile NP functionalization method can be used to fabricate protein resistant patterned surfaces to provide essentially complete control over cellular alignment, making them promising biofunctional structures for cell patterning. In another approach, I have utilized self-assembly of dendrimers and NPs without preformed templates to generate nanostructures that can be used as chemoselective membranes for the separation of small and biomacromolecules.

  20. Exosome Function: From Tumor Immunology to Pathogen Biology

    PubMed Central

    Schorey, Jeffrey S.; Bhatnagar, Sanchita

    2009-01-01

    Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Exosomes are derived from the fusion of multi-vesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell-to-cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intra-cellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates. PMID:18331451

  1. Functionalization of carbon nanotube and nanofiber electrodes with biological macromolecules: Progress toward a nanoscale biosensor

    NASA Astrophysics Data System (ADS)

    Baker, Sarah E.

    The integration of nanoscale carbon-based electrodes with biological recognition and electrical detection promises unparalleled biological detection systems. First, biologically modified carbon-based materials have been shown to have superior long-term chemical stability when compared to other commonly used materials for biological detection such as silicon, gold, and glass surfaces. Functionalizing carbon electrodes for biological recognition and using electrochemical methods to transduce biological binding information will enable real-time, hand-held, lower cost and stable biosensing devices. Nanoscale carbon-based electrodes allow the additional capability of fabricating devices with high densities of sensing elements, enabling multi-analyte detection on a single chip. We have worked toward the integration of these sensor components by first focusing on developing and characterizing the chemistry required to functionalize single-walled carbon nanotubes and vertically aligned carbon nanofibers with oligonucleotides and proteins for specific biological recognition. Chemical, photochemical and electrochemical methods for functionalizing these materials with biological molecules were developed. We determined, using fluorescence and colorimetric techniques, that these biologically modified nanoscale carbon electrodes are biologically active, selective, and stable. A photochemical functionalization method enabled facile functionalization of dense arrays vertically aligned carbon nanofiber forests. We found that much of the vertically aligned carbon nanofiber sidewalls were functionalized and biologically accessible by this method---the absolute number of DNA molecules hybridized to DNA-functionalized nanofiber electrodes was ˜8 times higher than the number of DNA molecules hybridized to flat glassy carbon electrodes and implies that nanofiber forest sensors may facilitate higher sensitivity to target DNA sequences per unit area. We also used the photochemical method

  2. Functional crosstalk between membrane lipids and TLR biology.

    PubMed

    Köberlin, Marielle S; Heinz, Leonhard X; Superti-Furga, Giulio

    2016-04-01

    Toll-like receptors (TLRs) are important transmembrane proteins of the innate immune system that detect invading pathogens and subsequently orchestrate an immune response. The ensuing inflammatory processes are connected to lipid metabolism at multiple levels. Here, we describe different aspects of how membrane lipids can shape the response of TLRs. Recent reports have uncovered the role of individual lipid species on membrane protein function and mouse models have contributed to the understanding of how changes in lipid metabolism alter TLR signaling, endocytosis, and cytokine secretion. Finally, we discuss the importance of systematic approaches to identify the function of individual lipid species or the composition of membrane lipids in TLR-related processes. PMID:26895312

  3. Biological/biomedical accelerator mass spectrometry targets. 1. optimizing the CO2 reduction step using zinc dust.

    PubMed

    Kim, Seung-Hyun; Kelly, Peter B; Clifford, Andrew J

    2008-10-15

    Biological and biomedical applications of accelerator mass spectrometry (AMS) use isotope ratio mass spectrometry to quantify minute amounts of long-lived radioisotopes such as (14)C. AMS target preparation involves first the oxidation of carbon (in sample of interest) to CO 2 and second the reduction of CO 2 to filamentous, fluffy, fuzzy, or firm graphite-like substances that coat a -400-mesh spherical iron powder (-400MSIP) catalyst. Until now, the quality of AMS targets has been variable; consequently, they often failed to produce robust ion currents that are required for reliable, accurate, precise, and high-throughput AMS for biological/biomedical applications. Therefore, we described our optimized method for reduction of CO 2 to high-quality uniform AMS targets whose morphology we visualized using scanning electron microscope pictures. Key features of our optimized method were to reduce CO 2 (from a sample of interest that provided 1 mg of C) using 100 +/- 1.3 mg of Zn dust, 5 +/- 0.4 mg of -400MSIP, and a reduction temperature of 500 degrees C for 3 h. The thermodynamics of our optimized method were more favorable for production of graphite-coated iron powders (GCIP) than those of previous methods. All AMS targets from our optimized method were of 100% GCIP, the graphitization yield exceeded 90%, and delta (13)C was -17.9 +/- 0.3 per thousand. The GCIP reliably produced strong (12)C (-) currents and accurate and precise F m values. The observed F m value for oxalic acid II NIST SRM deviated from its accepted F m value of 1.3407 by only 0.0003 +/- 0.0027 (mean +/- SE, n = 32), limit of detection of (14)C was 0.04 amol, and limit of quantification was 0.07 amol, and a skilled analyst can prepare as many as 270 AMS targets per day. More information on the physical (hardness/color), morphological (SEMs), and structural (FT-IR, Raman, XRD spectra) characteristics of our AMS targets that determine accurate, precise, and high-hroughput AMS measurement are in the

  4. Biological factors of natural and artificial ecosystems stable (unstable) functioning

    NASA Astrophysics Data System (ADS)

    Pechurkin, Nikolai S.

    The problem of sustainable development of humanity on Earth and the problem of supporting human life in space have the same scientific and methodological bases. The key to solve both problems is a long term maintenance of balanced material cycle. As a whole, natural or artificial ecosystems are to be more closed than open, but their elements (links of systems) are to be substantially open in interactions with each other. Prolonged stable interactions of different links have to have unique joint results - closed material cycling or biotic turnover. It is necessary to include, at least, three types of main links into any system to support real material cycling: producers, consumers, reducers. Producer links are now under studies in many laboratories. It is evident that the higher productivity of link, the lower link stability. Especially, it concerns with parasite impact to plants. As usual, artificial ecosystems are more simple (incomplete) than natural ecosystems, sometimes, they have not enough links for prolonged stable functioning. For example, life support system for space flight can be incomplete in consumer link, having only some crew persons, instead of interacting populations of consumers. As for reducer link, it is necessary to "organize" a special coordinated work of microbial biocenoses to fulfill proper cycling. Possible evolution of links, their self development is a matter of special attention for the maintenance of prolonged stable functioning. It's the most danger for systems with populations of quickly reproducing, so-called, R - strategists, according to symbols of logistic equation. From another side, quick reproduction of R - strategists is able to increase artificial ecosystems and their links functioning. After some damages of system, R - strategist's link can be quickly "self repaired" up to level of normal functioning. Some experimental data of this kind and mathematical models are to be discussed in the paper. This work is supported by

  5. Functional Nanostructured Platforms for Chemical and Biological Sensing

    SciTech Connect

    Letant, S E

    2006-03-20

    The central goal of our work is to combine semiconductor nanotechnology and surface functionalization in order to build platforms for the selective detection of bio-organisms ranging in size from bacteria (micron range) down to viruses, as well as for the detection of chemical agents (nanometer range). We will show on three porous silicon platforms how pore geometry and pore wall chemistry can be combined and optimized to capture and detect specific targets. We developed a synthetic route allowing to directly anchor proteins on silicon surfaces and illustrated the relevance of this technique by immobilizing live enzymes onto electrochemically etched luminescent nano-porous silicon. The powerful association of the specific enzymes with the transducing matrix led to a selective hybrid platform for chemical sensing. We also used light-assisted electrochemistry to produce periodic arrays of through pores on pre-patterned silicon membranes with controlled diameters ranging from many microns down to tens of nanometers. We demonstrated the first covalently functionalized silicon membranes and illustrated their selective capture abilities with antibody-coated micro-beads. These engineered membranes are extremely versatile and could be adapted to specifically recognize the external fingerprints (size and coat composition) of target bio-organisms. Finally, we fabricated locally functionalized single nanopores using a combination of focused ion beam drilling and ion beam assisted oxide deposition. We showed how a silicon oxide ring can be grown around a single nanopore and how it can be functionalized with DNA probes to detect single viral-sized beads. The next step for this platform is the detection of whole viruses and bacteria.

  6. Functional nanostructured platforms for chemical and biological sensing

    NASA Astrophysics Data System (ADS)

    Létant, S. E.

    2006-05-01

    The central goal of our work is to combine semiconductor nanotechnology and surface functionalization in order to build platforms for the selective detection of bio-organisms ranging in size from bacteria (micron range) down to viruses, as well as for the detection of chemical agents (nanometer range). We will show on three porous silicon platforms how pore geometry and pore wall chemistry can be combined and optimized to capture and detect specific targets. We developed a synthetic route allowing to directly anchor proteins on silicon surfaces and illustrated the relevance of this technique by immobilizing live enzymes onto electrochemically etched luminescent nano-porous silicon. The powerful association of the specific enzymes with the transducing matrix led to a selective hybrid platform for chemical sensing. We also used light-assisted electrochemistry to produce periodic arrays of through pores on pre-patterned silicon membranes with controlled diameters ranging from many microns down to tens of nanometers. We demonstrated the first covalently functionalized silicon membranes and illustrated their selective capture abilities with antibody-coated micro-beads. These engineered membranes are extremely versatile and could be adapted to specifically recognize the external fingerprints (size and coat composition) of target bio-organisms. Finally, we fabricated locally functionalized single nanopores using a combination of focused ion beam drilling and ion beam assisted oxide deposition. We showed how a silicon oxide ring can be grown around a single nanopore and how it can be functionalized with DNA probes to detect single viral-sized beads. The next step for this platform is the detection of whole viruses and bacteria.

  7. Density functional theory across chemistry, physics and biology

    PubMed Central

    van Mourik, Tanja; Bühl, Michael; Gaigeot, Marie-Pierre

    2014-01-01

    The past decades have seen density functional theory (DFT) evolve from a rising star in computational quantum chemistry to one of its major players. This Theme Issue, which comes half a century after the publication of the Hohenberg–Kohn theorems that laid the foundations of modern DFT, reviews progress and challenges in present-day DFT research. Rather than trying to be comprehensive, this Theme Issue attempts to give a flavour of selected aspects of DFT. PMID:24516181

  8. STRIPAK Complexes: structure, biological function, and involvement in human diseases

    PubMed Central

    Hwang, Juyeon; Pallas, David C.

    2014-01-01

    The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK–like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK or STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we will explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation. PMID:24333164

  9. Density functional theory across chemistry, physics and biology.

    PubMed

    van Mourik, Tanja; Bühl, Michael; Gaigeot, Marie-Pierre

    2014-03-13

    The past decades have seen density functional theory (DFT) evolve from a rising star in computational quantum chemistry to one of its major players. This Theme Issue, which comes half a century after the publication of the Hohenberg-Kohn theorems that laid the foundations of modern DFT, reviews progress and challenges in present-day DFT research. Rather than trying to be comprehensive, this Theme Issue attempts to give a flavour of selected aspects of DFT. PMID:24516181

  10. Electrical stimulation accelerates axonal and functional peripheral nerve regeneration across long gaps.

    PubMed

    Haastert-Talini, Kirsten; Schmitte, Ruth; Korte, Nele; Klode, Dorothee; Ratzka, Andreas; Grothe, Claudia

    2011-04-01

    Short-term low-frequency electrical stimulation (ESTIM) of proximal peripheral nerve stumps prior to end-to-end coaptation or tubular bridging of small distances has been reported to increase preferential motor reinnervation and functional motor recovery in animal models and human patients undergoing carpal tunnel release surgery. We investigated the effects of ESTIM on regeneration across rat sciatic nerve gaps, which exceed distances that allow spontaneous regeneration. Three different reconstruction approaches were combined with ESTIM in the experimental groups. Nerve gaps (13 mm) were bridged using (I) nerve autotransplantation, (II) transplantation of differentially filled silicone tubes, or (III) transplantation of tubular grafts containing fibroblast growth factor-2 overexpressing Schwann cells (SCs) for gene therapy. The regeneration outcome was followed for up to 8 weeks, and functionally as well as histomorphometrically analyzed in comparison to non-stimulated control groups. Combining ESTIM with nerve autotransplantation significantly increased the nerve fiber density in the regenerated nerve, and the grade of functional recovery as detected by electrodiagnostic recordings from the gastrocnemius muscle. The combination of ESTIM with transplantation of naïve SCs increased the regeneration of gap-bridging nerve tissue. Although macroscopic tissue regeneration was not further improved after combining ESTIM with FGF-2(21/23-kD) gene therapy, the latter resulted in a high rate of regenerated nerves that functionally reconnected to the target muscle. Based on our results, brief ESTIM shows high potential to accelerate axonal as well as functional (motor and sensory) outcomes in the clinical setting of peripheral nerve gap reconstruction in human patients. PMID:21265597

  11. Effects of mechanical ventilation on diaphragm function and biology.

    PubMed

    Gayan-Ramirez, G; Decramer, M

    2002-12-01

    The pathophysiological mechanisms of weaning from mechanical ventilation are not fully known, but there is accumulating evidence that mechanical ventilation induces inspiratory muscle dysfunction. Recently, several animal models have provided potential mechanisms for mechanical ventilation-induced effects on muscle function. In patients, weaning difficulties are associated with inspiratory muscle weakness and reduced endurance capacity. Animal studies demonstrated that diaphragm force was already decreased after 12 h of controlled mechanical ventilation and this worsened with time spent on the ventilator. Diaphragmatic myofibril damage observed after 3-days controlled mechanical ventilation was inversely correlated with maximal diaphragmatic force. Downregulation of the diaphragm insulin-like growth factor-I and MyoD/myogenin messenger ribonucleic acid occurred after 24 h and diaphragmatic oxidative stress and increased protease activity after 18 h. In keeping with these findings, diaphragm fibre atrophy was shown after 12 h and reduced diaphragm mass was reported after 48 h of controlled mechanical ventilation. These animal studies show that early alterations in diaphragm function develop after short-term mechanical ventilation. These alterations may contribute to the difficulties in weaning from mechanical ventilation seen in patients. Strategies to preserve respiratory muscle mass and function during mechanical ventilation should be developed. These may include: adaptation of medication, training of the diaphragm, stabilisation of the catabolic state and pharmacotherapy. PMID:12503720

  12. Oxygen flux analysis to understand the biological function of sirtuins.

    PubMed

    Wang, Dongning; Green, Michelle F; McDonnell, Eoin; Hirschey, Matthew D

    2013-01-01

    The sirtuins are a family of highly conserved NAD(+)-dependent lysine deacylases with important roles in metabolic regulation. Of the seven mammalian sirtuins, three localize to the mitochondria: SIRT3, SIRT4, and SIRT5. Mitochondrial sirtuins are crucial regulators of the metabolic network that controls energy homeostasis and impacts cancer, obesity, diabetes, mitochondrial diseases, metabolic disorders, and many other human diseases of aging. To best study the mitochondrial function of the sirtuins, we have employed an oxygen flux analyzer as a tool to track and record the extracellular oxygen consumption rate and acidification rate that reflects mitochondrial respiration and glycolysis, respectfully. Here we described the methods using this assay to study the substrate utilization and mitochondrial function in a human hepatocellular carcinoma cell line, Huh7. Additionally, we have generated a stable SIRT4 knocked-down Huh7 cell line. With this cell line, we evaluated how the absence of SIRT4 affects mitochondrial function, glucose utilization, glutamine oxidation, and fatty acid oxidation in these cells. PMID:24014411

  13. Resilin-Like Polypeptide Hydrogels Engineered for Versatile Biological Functions.

    PubMed

    Li, Linqing; Tong, Zhixiang; Jia, Xinqiao; Kiick, Kristi L

    2013-01-01

    Natural resilin, the rubber-like protein that exists in specialized compartments of most arthropods, possesses excellent mechanical properties such as low stiffness, high resilience and effective energy storage. Recombinantly-engineered resilin-like polypeptides (RLPs) that possess the favorable attributes of native resilin would be attractive candidates for the modular design of biomaterials for engineering mechanically active tissues. Based on our previous success in creating a novel RLP-based hydrogel and demonstrating useful mechanical and cell-adhesive properties, we have produced a suite of new RLP-based constructs, each equipped with 12 repeats of the putative resilin consensus sequence and a single, distinct biologically active domain. This approach allows independent control over the concentrations of cell-binding, MMP-sensitive, and polysaccharide-sequestration domains in hydrogels comprising mixtures of the various RLPs. The high purity, molecular weight and correct compositions of each new polypeptide have been confirmed via high performance liquid chromatography (HPLC), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), and amino acid analysis. These RLP-based polypeptides exhibit largely random-coil conformation, both in solution and in the cross-linked hydrogels, as indicated by circular dichroic and infrared spectroscopic analyses. Hydrogels of various compositions, with a range of elastic moduli (1kPa to 25kPa) can be produced from these polypeptides, and the activity of the cell-binding and matrix metalloproteinase (MMP) sensitive domains was confirmed. Tris(hydroxymethyl phosphine) cross-linked RLP hydrogels were able to maintain their mechanical integrity as well as the viability of encapsulated primary human mesenchymal stem cells (MSCs). These results validate the promising properties of these RLP-based elastomeric biomaterials. PMID:23505396

  14. Rapidly restoring biological soil crusts and ecosystem functions in a severely disturbed desert ecosystem.

    PubMed

    Chiquoine, Lindsay P; Abella, Scott R; Bowker, Matthew A

    2016-06-01

    Restoring biological soil crusts (biocrusts) in degraded drylands can contribute to recovery of ecosystem functions that have global implications, including erosion resistance and nutrient cycling. To examine techniques for restoring biocrusts, we conducted a replicated, factorial experiment on recently abandoned road surfaces by applying biocrust inoculation (salvaged and stored dry for two years), salvaged topsoil, an abiotic soil amendment (wood shavings), and planting of a dominant perennial shrub (Ambrosia dumosa). Eighteen months after treatments, we measured biocrust abundance and species composition, soil chlorophyll a content and fertility, and soil resistance to erosion. Biocrust addition significantly accelerated biocrust recovery on disturbed soils, including increasing lichen and moss cover and cyanobacteria colonization. Compared to undisturbed controls, inoculated plots had similar lichen and moss composition, recovered 43% of total cyanobacteria density, had similar soil chlorophyll content, and exhibited recovery of soil fertility and soil stability. Inoculation was the only treatment that generated lichen and moss cover. Topsoil application resulted in partial recovery of the cyanobacteria community and soil properties. Compared to untreated disturbed plots, topsoil application without inoculum increased cyanobacteria density by 186% and moderately improved soil chlorophyll and ammonium content and soil stability. Topsoil application produced 22% and 51% of the cyanobacteria density g⁻¹ soil compared to undisturbed and inoculated plots, respectively. Plots not treated with either topsoil or inoculum had significantly lower cyanobacteria density, soil chlorophyll and ammonium concentrations, and significantly higher soil nitrate concentration. Wood shavings and Ambrosia had no influence on biocrust lichen and moss species recovery but did affect cyanobacteria composition and soil fertility. Inoculation of severely disturbed soil with native

  15. [Dialectic of the interrelationship between structure and function in biology and medicine].

    PubMed

    Strukov, A I; Kakturskiĭ, L V

    1977-01-01

    The paper deals with some aspects of the dialectics of structure and function relationships in biological objects normally and pathologically. Idealistic and metaphysical concepts of the structure-function relationships (morphological idealism, holism, physiological idealism, functionalism) are critisized, and historical premises of these concepts are characterized. The principle of indissoluble unity and interconnection of changes in structure and function is emphasized, while the thesis of the primacy of function in the shaping of the form and the concept of functional diseases are rejected. Much attention is paid to the methodological principles of the study of structure and function based on the systemic approach to the investigation of biological objects from the point of view of structural levels and integratism. The groundlessness of the principles of reductionism and organicism in the solution of this problem is indicated. The connection of the concepts of structure and function with categories and laws of materialistic dialectics is dwelt on. PMID:880057

  16. Spruce Budworm (Lepidoptera: Tortricidae) Oral Secretions I: Biology and Function.

    PubMed

    Eveleigh, Eldon; Silk, Peter; Leclair, Gaëtan; Mayo, Peter; Francis, Brittany; Williams, Martin

    2015-12-01

    The potential roles of the oral secretions (OS) of spruce budworm (SBW; Choristoneura fumiferana Clemens) larvae and factors that may affect the volume of OS disgorged were investigated in the laboratory. Experiments revealed that diet-fed SBW larvae readily disgorge OS when induced ("milked"), with minimal overall cost to their development and eventual pupal weight. Exposure of conspecific larvae to OS throughout larval development negatively affected survival and male pupal weight; however, male development time was faster when exposed to OS. Female pupal weight and development time were not affected. Preliminary experiments suggested that OS had a repellent effect on a co-occurring herbivore, the false hemlock looper, Nepytia canosaria (Walker). OS produced by larvae that fed on three host tree species and on artificial diet significantly increased the grooming time of ants (Camponotus sp.), indicating that SBW OS have an anti-predator function. The volume of OS is significantly greater in L6 than in L4 or L5, with the volume produced by L6 depending on weight and age as well as feeding history at time of milking. These findings indicate that SBW OS function as both an intra- and interspecific epideictic pheromone and as an anti-predator defensive mechanism, while incurring minimal metabolic costs. PMID:26454475

  17. Estrogen Biology: New Insights into GPER Function and Clinical Opportunities

    PubMed Central

    Prossnitz, Eric R.; Barton, Matthias

    2014-01-01

    Estrogens play an important role in the regulation of normal physiology, aging and many disease states. Although the nuclear estrogen receptors have classically been described to function as ligand-activated transcription factors mediating genomic effects in hormonally regulated tissues, more recent studies reveal that estrogens also mediate rapid signaling events traditionally associated with G protein-coupled receptors. The G protein-coupled estrogen receptor GPER (formerly GPR30) has now become recognized as a major mediator of estrogen’s rapid cellular effects throughout the body. With the discovery of selective synthetic ligands for GPER, both agonists and antagonists, as well as the use of GPER knockout mice, significant advances have been made in our understanding of GPER function at the cellular, tissue and organismal levels. In many instances, the protective/beneficial effects of estrogen are mimicked by selective GPER agonism and are absent or reduced in GPER knockout mice, suggesting an essential or at least parallel role for GPER in the actions of estrogen. In this review, we will discuss recent advances and our current understanding of the role of GPER and certain drugs such as SERMs and SERDs in physiology and disease. We will also highlight novel opportunities for clinical development towards GPER-targeted therapeutics, for molecular imaging, as well as for theranostic approaches and personalized medicine. PMID:24530924

  18. The biomolecule ubiquinone exerts a variety of biological functions.

    PubMed

    Nohl, Hans; Staniek, Katrin; Kozlov, Andrey V; Gille, Lars

    2003-01-01

    The chemistry of ubiquinone allows reversible addition of single electrons and protons. This unique property is used in nature for aerobic energy gain, for unilateral proton accumulation, for the generation of reactive oxygen species involved in physiological signaling and a variety of pathophysiological events. Since several years ubiquinone is also considered to play a major role in the control of lipid peroxidation, since this lipophilic biomolecule was recognized to recycle alpha-tocopherol radicals back to the chain-breaking form, vitamin E. Ubiquinone is therefore a biomolecule which has increasingly focused the interest of many research groups due to its alternative pro- and antioxidant activity. We have intensively investigated the role of ubiquinone as prooxidant in mitochondria and will present experimental evidences on conditions required for this function, we will also show that lysosomal ubiquinone has a double function as proton translocator and radical source under certain metabolic conditions. Furthermore, we have addressed the antioxidant role of ubiquinone and found that the efficiency of this activity is widely dependent on the type of biomembrane where ubiquinone exerts its chain-breaking activity. PMID:14695917

  19. Assessment of the setup dependence of detector response functions for mega-voltage linear accelerators

    SciTech Connect

    Fox, Christopher; Simon, Tom; Simon, Bill; Dempsey, James F.; Kahler, Darren; Palta, Jatinder R.; Liu Chihray; Yan Guanghua

    2010-02-15

    Purpose: Accurate modeling of beam profiles is important for precise treatment planning dosimetry. Calculated beam profiles need to precisely replicate profiles measured during machine commissioning. Finite detector size introduces perturbations into the measured profiles, which, in turn, impact the resulting modeled profiles. The authors investigate a method for extracting the unperturbed beam profiles from those measured during linear accelerator commissioning. Methods: In-plane and cross-plane data were collected for an Elekta Synergy linac at 6 MV using ionization chambers of volume 0.01, 0.04, 0.13, and 0.65 cm{sup 3} and a diode of surface area 0.64 mm{sup 2}. The detectors were orientated with the stem perpendicular to the beam and pointing away from the gantry. Profiles were measured for a 10x10 cm{sup 2} field at depths ranging from 0.8 to 25.0 cm and SSDs from 90 to 110 cm. Shaping parameters of a Gaussian response function were obtained relative to the Edge detector. The Gaussian function was deconvolved from the measured ionization chamber data. The Edge detector profile was taken as an approximation to the true profile, to which deconvolved data were compared. Data were also collected with CC13 and Edge detectors for additional fields and energies on an Elekta Synergy, Varian Trilogy, and Siemens Oncor linear accelerator and response functions obtained. Response functions were compared as a function of depth, SSD, and detector scan direction. Variations in the shaping parameter were introduced and the effect on the resulting deconvolution profiles assessed. Results: Up to 10% setup dependence in the Gaussian shaping parameter occurred, for each detector for a particular plane. This translated to less than a {+-}0.7 mm variation in the 80%-20% penumbral width. For large volume ionization chambers such as the FC65 Farmer type, where the cavity length to diameter ratio is far from 1, the scan direction produced up to a 40% difference in the shaping

  20. Impaired motor function in senescence-accelerated mouse prone 1 (SAMP1).

    PubMed

    Aoyama, Yo; Kim, Tae Yeon; Yoshimoto, Takuro; Niimi, Kimie; Takahashi, Eiki; Itakura, Chitoshi

    2013-06-17

    Senescence-accelerated mouse prone (SAMP) strains of mice show early onset of senescence, whereas senescence-accelerated mouse resistant (SAMR) strains are resistant to early senescence and serve as controls. Although SAMP6 and SAMP8 are established models of central nervous system alterations, it is unclear whether SAMP1/Sku (SAMP1) is characterized by brain alterations and dysfunction related to behavioral functioning. In the present study, behavioral tests (i.e., locomotor activity, Y-maze, rotating rod, hind-limb extension, and traction), histochemistry, and Western blot analyses were employed to study this mouse model using 2- and 4-month-old SAMP1 and age-matched control SAMR1. Although 2-month-old SAMP1 and SAMR1 showed similar activity, 4-month-old SAMP1 exhibited less activity than age-matched SAMR1 in locomotor activity and Y-maze tests. In rotating rod test, 2- and 4-month-old SAMP1 showed motor-coordination dysfunction. An abnormal extension reflex in the hind-limb test was observed in 2- and 4-month-old SAMP1. There were no significant differences between SAMP1 and SAMR1 with respect to grip strength in the traction test or alternation behavior in the Y-maze test. Histochemistry and Western blot analyses exhibited that cerebellar Purkinje cells in 4-month-old SAMP1 mice persistently expressed tyrosine hydroxylase. These results suggest that SAMP1 is a useful model for examining mechanisms underlying motor dysfunction. PMID:23583482

  1. Solar wind acceleration obtained from kinetic models based on electron velocity distribution functions with suprathermal particles

    NASA Astrophysics Data System (ADS)

    Pierrard, V.; Pieters, M.; Lazar, M.; Voitenko, Y.; Lamy, H.; Echim, M.

    2014-12-01

    Astrophysical and space plasmas are commonly found to be out ofthermal equilibrium, i.e., the velocity distribution functions (VDF)of plasma particles cannot be described well enough by Maxwelliandistribution functions. The suprathermal populations are ubiquitousenhancing the high-energy tail of the distribution. A kinetic model has been developed to successfullydescribe such plasmas with tails decreasing as a power law of thevelocity. In the present work, we show that a natural heating ofsolar and stellar coronas automatically appears when an enhancedpopulation of suprathermal particles is present at low altitude inthe solar (or stellar) atmosphere. This is true not only forelectrons and protons, but also for the minor ions which exhibit atemperature increase proportional to their mass. Moreover,suprathermal electrons contribute to the acceleration of stellarwinds to high bulk velocities when Coulomb collisions are neglected.These results are illustrated by using a global model of the solarcorona and solar wind based on VDF with suprathermal tails for thedifferent particle species. The energetic particles are non-collisional (without Coulomb collisions) even when thermalparticles are submitted to collisions. In the presence of long-rangecorrelations supplied by the fields and plasma instabilities,turbulence can play a role in the generation of such suprathermaltails. Solar wind observations are used as boundary conditions to determine the VDF in the other regions of the heliosphere. Consequences of suprathermal particles are also illustratedfor other space plasmas like the plasmasphere and the polar wind ofthe Earth and other planets.

  2. Structure determination of chemisorbed chirality transfer complexes: Accelerated STM analysis and exchange-correlation functional sensitivity

    NASA Astrophysics Data System (ADS)

    Groves, M. N.; Goubert, G.; Rasmussen, A. M. H.; Dong, Y.; Lemay, J.-C.; Demers-Carpentier, V.; McBreen, P. H.; Hammer, B.

    2014-11-01

    Linking STM images to atomic positions determined by DFT calculations is an important step in characterizing the intermolecular interactions at play in many surface processes including asymmetric hydrogenation on heterogeneous catalysts. An accelerated data extraction method is used to collect STM information on the geometry of complexes formed between the two substrates, 2,2,2-trifluoroacetophenone (TFAP) and 3,3,3-methyltrifluoropyruvate (MTFP), and the chiral modifier (R)-(+)-1-(1-naphthyl)ethylamine ((R)-NEA) on Pt(111). We present new experimental data for complexes formed by MTFP and the (R)-NEA-1 conformer along with a new and enlarged set of reformulated STM data that extends what was reported in previously published studies of complexed MTFP and TFAP. Atomic geometries based on DFT calculations using PBE, M06-L, and optB88-vdW exchange-correlation functionals will also be presented. It will be shown that both substrates have well-defined complexation geometries when interacting with the modifier and that the relative complexation energies are not markedly sensitive to the functional employed.

  3. The functions of biological diversity in an age of extinction.

    PubMed

    Naeem, Shahid; Duffy, J Emmett; Zavaleta, Erika

    2012-06-15

    Ecosystems worldwide are rapidly losing taxonomic, phylogenetic, genetic, and functional diversity as a result of human appropriation of natural resources, modification of habitats and climate, and the spread of pathogenic, exotic, and domestic plants and animals. Twenty years of intense theoretical and empirical research have shown that such biotic impoverishment can markedly alter the biogeochemical and dynamic properties of ecosystems, but frontiers remain in linking this research to the complexity of wild nature, and in applying it to pressing environmental issues such as food, water, energy, and biosecurity. The question before us is whether these advances can take us beyond merely invoking the precautionary principle of conserving biodiversity to a predictive science that informs practical and specific solutions to mitigate and adapt to its loss. PMID:22700920

  4. Structure and biological functions of keratan sulfate proteoglycans.

    PubMed

    Greiling, H

    1994-01-01

    The skeletal and corneal keratan sulfate proteoglycans show a different metabolic and structural heterogeneity. The domain structure of the carbohydrate chain has been shown to be different in various animal species. There are two major types of skeletal keratan sulfate proteoglycans with and without fucose. The protein cores of the corneal chicken keratan sulfate proteoglycan (lumican) and those of another small keratan sulfate proteoglycan (fibromodulin) have been sequenced. Keratan sulfate oligosaccharides belong to the members of an antigen family of the poly-N-acetyllactosamine series. Monoclonal antibodies and immunoassay procedures for keratan sulfate proteoglycans have been prepared. In osteoarthritis, no significant specific increase of keratan sulfate has been found. Keratan sulfate is a functional substitute for chondroitin sulfate in O2-deficient tissues. PMID:8298243

  5. The biology and function of exosomes in cancer.

    PubMed

    Kalluri, Raghu

    2016-04-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients. PMID:27035812

  6. Re-Annotation Is an Essential Step in Systems Biology Modeling of Functional Genomics Data

    PubMed Central

    van den Berg, Bart H. J.; McCarthy, Fiona M.; Lamont, Susan J.; Burgess, Shane C.

    2010-01-01

    One motivation of systems biology research is to understand gene functions and interactions from functional genomics data such as that derived from microarrays. Up-to-date structural and functional annotations of genes are an essential foundation of systems biology modeling. We propose that the first essential step in any systems biology modeling of functional genomics data, especially for species with recently sequenced genomes, is gene structural and functional re-annotation. To demonstrate the impact of such re-annotation, we structurally and functionally re-annotated a microarray developed, and previously used, as a tool for disease research. We quantified the impact of this re-annotation on the array based on the total numbers of structural- and functional-annotations, the Gene Annotation Quality (GAQ) score, and canonical pathway coverage. We next quantified the impact of re-annotation on systems biology modeling using a previously published experiment that used this microarray. We show that re-annotation improves the quantity and quality of structural- and functional-annotations, allows a more comprehensive Gene Ontology based modeling, and improves pathway coverage for both the whole array and a differentially expressed mRNA subset. Our results also demonstrate that re-annotation can result in a different knowledge outcome derived from previous published research findings. We propose that, because of this, re-annotation should be considered to be an essential first step for deriving value from functional genomics data. PMID:20498845

  7. Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair.

    PubMed

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2014-06-27

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: (1) scleraxis-expressing cells; (2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and (3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. PMID:24200342

  8. Functional Tissue Engineering of Tendon: Establishing Biological Success Criteria for Improving Tendon Repair

    PubMed Central

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2013-01-01

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: 1) scleraxis-expressing cells; 2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and 3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. PMID:24200342

  9. Biological Functions of the Genes in the Mammaprint Breast Cancer Profile Reflect the Hallmarks of Cancer

    PubMed Central

    Tian, Sun; Roepman, Paul; van’t Veer, Laura J; Bernards, Rene; de Snoo, Femke; Glas, Annuska M

    2010-01-01

    Background: MammaPrint was developed as a diagnostic tool to predict risk of breast cancer metastasis using the expression of 70 genes. To better understand the tumor biology assessed by MammaPrint, we interpreted the biological functions of the 70-genes and showed how the genes reflect the six hallmarks of cancer as defined by Hanahan and Weinberg. Results: We used a bottom-up system biology approach to elucidate how the cellular processes reflected by the 70-genes work together to regulate tumor activities and progression. The biological functions of the genes were analyzed using literature research and several bioinformatics tools. Protein-protein interaction network analyses indicated that the 70-genes form highly interconnected networks and that their expression levels are regulated by key tumorigenesis related genes such as TP53, RB1, MYC, JUN and CDKN2A. The biological functions of the genes could be associated with the essential steps necessary for tumor progression and metastasis, and cover the six well-defined hallmarks of cancer, reflecting the acquired malignant characteristics of a cancer cell along with tumor progression and metastasis-related biological activities. Conclusion: Genes in the MammaPrint gene signature comprehensively measure the six hallmarks of cancer-related biology. This finding establishes a link between a molecular signature and the underlying molecular mechanisms of tumor cell progression and metastasis. PMID:21151591

  10. Selenium and arsenic in biology: their chemical forms and biological functions.

    PubMed

    Shibata, Y; Morita, M; Fuwa, K

    1992-01-01

    Based on the recent development of analytical methods, sensitive systems for the analysis and speciation of selenium and arsenic have been established. A palladium addition technique was developed for the accurate determination of selenium in biological samples using graphite furnace atomic absorption analysis. For the speciation of the elements, combined methods of HPLC either with ICP-AES or with ICP-MS were found to work well. These systems were applied to the elucidation of the chemical form of the elements in natural samples. Some chemical properties of the selenium-mercury complex in dolphin liver were elucidated: i.e., it was a cationic, water-soluble, low molecular weight compound containing selenium and mercury in a 1:1 molar ratio, and was shown to be different from a known selenium-mercury complex, bis(methylmercuric)selenide. The major selenium compound excreted in human urine was revealed to be other than any of those previously identified (TMSe, selenate, and selenite). TMSe, a suspected major metabolite in urine, was found, if at all, in low levels. The major water-soluble, and lipid-soluble arsenic compounds in a brown seaweed, U. pinnatifida (WAKAME), were rigorously identified, and the results were compared with other data on marine algae and animals. The major organic arsenic compounds (termed "arseno-sugars") in marine algae commonly contain 5-deoxy-5-dimethylarsinyl-ribofuranoside moiety. There are various kinds of arseno-sugar derivatives containing different side-chains attached to the anomeric position of the sugar, and the distribution of each arsenic species seems to be related to algal species. The arseno-sugar (A-XI) is present in every alga so far examined, is metabolized to lipids, and possibly may play some specific role in the algal cells. On the other hand, the major arsenic compound in fish, crustacea and molluscs has been identified as arsenobetaine, which is an arseno-analog of glycinebetaine, a very common osmo-regulator in