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Sample records for biologically relevant metal-based

  1. Making Plant Biology Curricula Relevant.

    ERIC Educational Resources Information Center

    Hershey, David R.

    1992-01-01

    Reviews rationale, purposes, challenges, and relevance of hands-on, plant biology curricula that have been developed in response to the limited use of plants in biology education. Discusses methods to maintain both instructional rigor and student interest in the following topics: cut flowers, container-growing media, fertilizers, hydroponics,…

  2. Biology relevant to space radiation

    SciTech Connect

    Fry, R.J.M.

    1996-08-01

    The biological effects of the radiations to which mankind on earth are exposed are becoming known with an increasing degree of detail. This knowledge is the basis of the estimates of risk that, in turn, fosters a comprehensive and evolving radiation protection system. The substantial body of information has been, and is being, applied to questions about the biological effects of radiation is space and the associated risk estimates. The purpose of this paper is not to recount all the biological effect of radiation but to concentrate on those that may occur as a result from exposure to the radiations encountered in space. In general, the biological effects of radiation in space are the same as those on earth. However, the evidence that the effects on certain tissues by the heaviest-charged particles can be interpreted on the basis of our knowledge about other high-LET radiation is equivocal. This specific question will be discussed in greater detail later. It is important to point out the that there are only limited data about the effects on humans of two components of the radiations in space, namely protons and heavy ions. Thus predictions of effects on space crews are based on experimental systems exposed on earth at rates and fluences that are higher than those in space and one the effects of gamma or x rays with estimates of the equivalent doses using quality factors.

  3. Biology relevant to space radiation

    SciTech Connect

    Fry, R.J.M.

    1997-04-30

    There are only very limited data on the health effects to humans from the two major components of the radiations in space, namely protons and heavy ions. As a result, predictions of the accompanying effects must be based either on (1) data generated through studies of experimental systems exposed on earth at rates and fluences higher than those in space, or (2) extrapolations from studies of gamma and x rays. Better information is needed about the doses, dose rates, and the energy and LET spectra of the radiations at the organ level that are anticipated to be encountered during extended space missions. In particular, there is a need for better estimates of the relationship between radiation quality and biological effects. In the case of deterministic effects, it is the threshold that is important. The possibility of the occurrence of a large solar particle event (SPE) requires that such effects be considered during extended space missions. Analyses suggest, however, that it is feasible to provide sufficient shielding so as to reduce such effects to acceptable levels, particularly if the dose rates can be limited. If these analyses prove correct, the primary biological risks will be the stochastic effects (latent cancer induction). The contribution of one large SPE to the risk of stochastic effects while undesirable will not be large in comparison to the potential total dose on a mission of long duration.

  4. Biologically Relevant Glycopeptides: Synthesis and Applications

    NASA Astrophysics Data System (ADS)

    Bennett, Clay S.; Payne, Richard J.; Koeller, Kathryn M.; Wong, Chi-Huey

    Over the past two decades interest in glycopeptides and glycoproteins has intensified, due in part to the development of new and efficient methods for the synthesis of these compounds. This includes a number of chemical and enzymatic techniques for incorporating glycosylation onto the peptide backbone as well as the introduction of powerful peptide ligation methods for the construction of glycoproteins. This review discusses these methods with a special emphasis on biologically relevant glycopeptides and glycoproteins. This includes the development of a number of antigens which hold promise as potential vaccines for HIV, cancer, or a host of other clinically important diseases. In addition the development of new antibiotics aimed at overcoming the problem of resistance will be discussed. Finally, chemical and enzymatic methods for the construction of glycopeptide mimetics will be described.

  5. Mammalian lipoxygenases and their biological relevance

    PubMed Central

    Kuhn, Hartmut; Banthiya, Swathi; van Leyen, Klaus

    2015-01-01

    Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. PMID:25316652

  6. Capillary electrochromatography of biologically relevant flavonoids.

    PubMed

    Stöggl, Wolfgang M; Huck, Christian W; Stecher, Günther; Bonn, Günther K

    2006-02-01

    Flavonoids were separated utilizing CEC technique. Baseline separation of biologically relevant flavonoids was obtained using a 100 microm ID fused-silica capillary filled with 3 microm Silica-C18 material and an optimized mobile phase comprising of 20 mM Tris-HCl (pH 6.5), ACN and water at a ratio of 10/40/50 v/v/v. Separations were carried out at 25 kV and a column temperature of 25 degrees C. The influence of relevant parameters for the CEC separation, such as buffer concentration, pH, separation voltage, and ACN concentration, was investigated and optimized. Dependencies of the electroendoosmotic flow (EOF) on these parameters and effects on the resolution of the analytes were studied. During analyses the solvents used for dissolving the samples turned out to have significant effects on the separation of flavonoids. The optimized system was then successfully used for the separation of the flavonoids epicatechin, myricetin, quercetin, naringenin, and hesperetin. CEC turned out to be a useful complementary tool for the economic analysis of flavonoids in addition to common HPLC, muHPLC, and CE methodologies. This method can be used for real applications in phytomics. PMID:16411273

  7. Teaching Secondary School Biology for Social Relevance.

    ERIC Educational Resources Information Center

    Meyer, G. Rex; And Others

    Since the 1960's biology teaching in secondary schools has been transformed from a formal approach reflecting the structure of the discipline and mirroring the concerns of the scientific community to a broad-based approach reflecting the concerns of society as a whole. The aim of biology education today is to heighten awareness, improve students'…

  8. Future development of biologically relevant dosimetry.

    PubMed

    Palmans, H; Rabus, H; Belchior, A L; Bug, M U; Galer, S; Giesen, U; Gonon, G; Gruel, G; Hilgers, G; Moro, D; Nettelbeck, H; Pinto, M; Pola, A; Pszona, S; Schettino, G; Sharpe, P H G; Teles, P; Villagrasa, C; Wilkens, J J

    2015-01-01

    Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented. PMID:25257709

  9. The Biological Relevance of Artificial Life: Lessons from Artificial Intelligence

    NASA Technical Reports Server (NTRS)

    Colombano, Silvano

    2000-01-01

    There is no fundamental reason why A-life couldn't simply be a branch of computer science that deals with algorithms that are inspired by, or emulate biological phenomena. However, if these are the limits we place on this field, we miss the opportunity to help advance Theoretical Biology and to contribute to a deeper understanding of the nature of life. The history of Artificial Intelligence provides a good example, in that early interest in the nature of cognition quickly was lost to the process of building tools, such as "expert systems" that, were certainly useful, but provided little insight in the nature of cognition. Based on this lesson, I will discuss criteria for increasing the biological relevance of A-life and the probability that this field may provide a theoretical foundation for Biology.

  10. Behavior of nanoceria in biologically-relevant environments

    SciTech Connect

    Kumar, Amit; Das, Soumen; Munusamy, Prabhakaran; Self, William; Baer, Donald R.; Sayle, Dean C.; Seal, Sudipta

    2014-09-08

    Cerium oxide nanoparticles (CNPs) have gained a considerable attention in biological research due to their anti-oxidant like behaviour and regenerative nature. The current literature on CNPs reports many successful attempts on harnessing the beneficial therapeutic properties in biology. However studies have also shown toxicity effect with some types of CNPs. This review discusses issues associated with the behaviours of CNPs in biological systems and identifies key knowledge gaps. We explore how salient physicochemical properties (size, surface chemistry, surface stabilizers) contribute to the potential positive and negative aspects of nanoceria in biological systems. Based on variations of results reported in the literature, important issues need to be addressed. Are we really studying the same particles with slight variations in size and physicochemical properties or do the particles being examined have fundamentally different behaviours? Are the variations observed in the result of differences in the initial properties of the particles or the results of downstream effects that emerge as the particles are prepared for specific studies and they interact with biological or other environmental moieties? How should particles be appropriately prepared for relevant environmental/toxicology/safety studies? It is useful to recognize that nanoparticles encompass some of the same complexities and variability associated with biological components

  11. Hands-on-Entropy, Energy Balance with Biological Relevance

    NASA Astrophysics Data System (ADS)

    Reeves, Mark

    2015-03-01

    Entropy changes underlie the physics that dominates biological interactions. Indeed, introductory biology courses often begin with an exploration of the qualities of water that are important to living systems. However, one idea that is not explicitly addressed in most introductory physics or biology textbooks is important contribution of the entropy in driving fundamental biological processes towards equilibrium. From diffusion to cell-membrane formation, to electrostatic binding in protein folding, to the functioning of nerve cells, entropic effects often act to counterbalance deterministic forces such as electrostatic attraction and in so doing, allow for effective molecular signaling. A small group of biology, biophysics and computer science faculty have worked together for the past five years to develop curricular modules (based on SCALEUP pedagogy). This has enabled students to create models of stochastic and deterministic processes. Our students are first-year engineering and science students in the calculus-based physics course and they are not expected to know biology beyond the high-school level. In our class, they learn to reduce complex biological processes and structures in order model them mathematically to account for both deterministic and probabilistic processes. The students test these models in simulations and in laboratory experiments that are biologically relevant such as diffusion, ionic transport, and ligand-receptor binding. Moreover, the students confront random forces and traditional forces in problems, simulations, and in laboratory exploration throughout the year-long course as they move from traditional kinematics through thermodynamics to electrostatic interactions. This talk will present a number of these exercises, with particular focus on the hands-on experiments done by the students, and will give examples of the tangible material that our students work with throughout the two-semester sequence of their course on introductory

  12. The allosteric modulation of lipases and its possible biological relevance

    PubMed Central

    Köhler, Jens; Wünsch, Bernhard

    2007-01-01

    Background During the development of an enantioselective synthesis using the lipase from Mucor miehei an unusual reaction course was observed, which was analyzed precisely. For the first time an allosteric modulation of a lipase changing its selectivity was shown. Theory Considering the biological relevance of the discovered regulation mechanism we developed a theory that describes the regulation of energy homeostasis and fat metabolism. Conclusion This theory represents a new approach to explain the cause of the metabolic syndrome and provides an innovative basis for further research activity. PMID:17825093

  13. 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.

  14. Behavioural biology: an effective and relevant conservation tool.

    PubMed

    Buchholz, Richard

    2007-08-01

    'Conservation behaviour' is a young discipline that investigates how proximate and ultimate aspects of the behaviour of an animal can be of value in preventing the loss of biodiversity. Rumours of its demise are unfounded. Conservation behaviour is quickly building a capacity to positively influence environmental decision making. The theoretical framework used by animal behaviourists is uniquely valuable to elucidating integrative solutions to human-wildlife conflicts, efforts to reintroduce endangered species and reducing the deleterious effects of ecotourism. Conservation behaviourists must join with other scientists under the multidisciplinary umbrella of conservation biology without giving up on their focus: the mechanisms, development, function and evolutionary history of individual differences in behaviour. Conservation behaviour is an increasingly relevant tool in the preservation of nature. PMID:17590477

  15. Biclustering Methods: Biological Relevance and Application in Gene Expression Analysis

    PubMed Central

    Oghabian, Ali; Kilpinen, Sami; Hautaniemi, Sampsa; Czeizler, Elena

    2014-01-01

    DNA microarray technologies are used extensively to profile the expression levels of thousands of genes under various conditions, yielding extremely large data-matrices. Thus, analyzing this information and extracting biologically relevant knowledge becomes a considerable challenge. A classical approach for tackling this challenge is to use clustering (also known as one-way clustering) methods where genes (or respectively samples) are grouped together based on the similarity of their expression profiles across the set of all samples (or respectively genes). An alternative approach is to develop biclustering methods to identify local patterns in the data. These methods extract subgroups of genes that are co-expressed across only a subset of samples and may feature important biological or medical implications. In this study we evaluate 13 biclustering and 2 clustering (k-means and hierarchical) methods. We use several approaches to compare their performance on two real gene expression data sets. For this purpose we apply four evaluation measures in our analysis: (1) we examine how well the considered (bi)clustering methods differentiate various sample types; (2) we evaluate how well the groups of genes discovered by the (bi)clustering methods are annotated with similar Gene Ontology categories; (3) we evaluate the capability of the methods to differentiate genes that are known to be specific to the particular sample types we study and (4) we compare the running time of the algorithms. In the end, we conclude that as long as the samples are well defined and annotated, the contamination of the samples is limited, and the samples are well replicated, biclustering methods such as Plaid and SAMBA are useful for discovering relevant subsets of genes and samples. PMID:24651574

  16. Biclustering methods: biological relevance and application in gene expression analysis.

    PubMed

    Oghabian, Ali; Kilpinen, Sami; Hautaniemi, Sampsa; Czeizler, Elena

    2014-01-01

    DNA microarray technologies are used extensively to profile the expression levels of thousands of genes under various conditions, yielding extremely large data-matrices. Thus, analyzing this information and extracting biologically relevant knowledge becomes a considerable challenge. A classical approach for tackling this challenge is to use clustering (also known as one-way clustering) methods where genes (or respectively samples) are grouped together based on the similarity of their expression profiles across the set of all samples (or respectively genes). An alternative approach is to develop biclustering methods to identify local patterns in the data. These methods extract subgroups of genes that are co-expressed across only a subset of samples and may feature important biological or medical implications. In this study we evaluate 13 biclustering and 2 clustering (k-means and hierarchical) methods. We use several approaches to compare their performance on two real gene expression data sets. For this purpose we apply four evaluation measures in our analysis: (1) we examine how well the considered (bi)clustering methods differentiate various sample types; (2) we evaluate how well the groups of genes discovered by the (bi)clustering methods are annotated with similar Gene Ontology categories; (3) we evaluate the capability of the methods to differentiate genes that are known to be specific to the particular sample types we study and (4) we compare the running time of the algorithms. In the end, we conclude that as long as the samples are well defined and annotated, the contamination of the samples is limited, and the samples are well replicated, biclustering methods such as Plaid and SAMBA are useful for discovering relevant subsets of genes and samples. PMID:24651574

  17. Identifying Biologically Relevant Cues in the Hydrologic Regime

    NASA Astrophysics Data System (ADS)

    Lovellford, R. M.; Flitcroft, R.; Santelmann, M. V.; Grant, G. E.; Safeeq, M.; Lewis, S.

    2012-12-01

    Seasonal variation in hydrologic discharge and temperature defines the availability, connectivity, and quality of lentic habitats. Native aquatic species are adapted to local hydrologic regimes , eg. magnitudes and rates of change . In recent decades, biologically relevant hydrologic conditions have been identified that are necessary to maintain habitat conditions for aquatic obligate species. Another element of hydrologic regimes important to aquatic species are the cues that inform individuals of seasonal changes that precipitate important physiological or behavioral alterations. There is a need for hydrologists, biologists, and ecologists, to define biologically significant cues within the hydrologic regime. Coho salmon (Onchorhynchus kisutch), an anadromous species of Pacific salmon, offers an example of sensitivity to environmental cues. Examinations of the run-timing of mature adult coho salmon on the North Umpqua River, OR, indicate that migration timing coincides with decreasing fall water temperatures prior to increasing winter discharge. For this species, adults leave the ocean ready to spawn. Adults need to spawn in small headwater streams prior to the onset of intense storm conditions that prohibit effective deposition or fertilization of eggs in redds (salmon nests).Therefore, the timing of spawning must be carefully executed. Understanding the cues that trigger specific behaviors gives insight to the processes that provide ecosystem stability and flexibility over time. Improved understanding of these cues may help us protect freshwater ecosystems and improve management for endangered species.

  18. Biological and clinical relevance of stem cells in pancreatic adenocarcinoma

    PubMed Central

    Rasheed, Zeshaan A; Matsui, William

    2013-01-01

    Cancer stem cells (CSC) have been identified in a growing number of human malignancies. CSC are functionally defined by their ability to self-renew and recapitulate tumors in the ectopic setting, and a growing number of studies have shown that they display other functional characteristics, such as invasion and drug resistance. These unique functional properties implicate a role for CSC in clinical consequences, such as initial tumor formation, relapse following treatment, metastasis, and resistance, suggesting they are a major factor in directing clinical outcomes. Pancreatic adenocarcinoma is a highly-aggressive disease with a propensity for early metastasis and drug resistance. Tumorigenic pancreatic cancer cells have been identified using the cell surface antigens CD44, CD24, and CD133, as well as the high expression of aldehyde dehydrogenase (ALDH). In vitro and in vivo studies have shown that ALDH- and CD133-expressing pancreatic CSC have a greater propensity for metastasis, and ALDH-expressing CSC have been shown to be resistant to conventional chemotherapy. In clinical samples from patients with resected pancreatic adenocarcinoma, the presence of ALDH-expressing CSC was associated with worse overall survival. The development of CSC-targeting therapies might be important in changing the clinical outcomes of patients with this disease, and others and we have begun to identify novel compounds that block CSC function. This review will discuss the biological and clinical relevance of CSC in pancreatic cancer, and will discuss novel therapeutic strategies to target them. PMID:22320910

  19. Characterization of Nanoparticle Aggregation in Biologically Relevant Fluids

    NASA Astrophysics Data System (ADS)

    McEnnis, Kathleen; Lahann, Joerg

    Nanoparticles (NPs) are often studied as drug delivery vehicles, but little is known about their behavior in blood once injected into animal models. If the NPs aggregate in blood, they will be shunted to the liver or spleen instead of reaching the intended target. The use of animals for these experiments is costly and raises ethical questions. Typically dynamic light scattering (DLS) is used to analyze aggregation behavior, but DLS cannot be used because the components of blood also scatter light. As an alternative, a method of analyzing NPs in biologically relevant fluids such as blood plasma has been developed using nanoparticle tracking analysis (NTA) with fluorescent filters. In this work, NTA was used to analyze the aggregation behavior of fluorescent polystyrene NPs with different surface modifications in blood plasma. It was expected that different surface chemistries on the particles will change the aggregation behavior. The effect of the surface modifications was investigated by quantifying the percentage of NPs in aggregates after addition to blood plasma. The use of this characterization method will allow for better understanding of particle behavior in the body, and potential problems, specifically aggregation, can be addressed before investing in in vivo studies.

  20. Reviewing the relevance of fluorescence in biological systems.

    PubMed

    Lagorio, M Gabriela; Cordon, Gabriela B; Iriel, Analia

    2015-09-26

    Fluorescence is emitted by diverse living organisms. The analysis and interpretation of these signals may give information about their physiological state, ways of communication among species and the presence of specific chemicals. In this manuscript we review the state of the art in the research on the fluorescence emitted by plant leaves, fruits, flowers, avians, butterflies, beetles, dragonflies, millipedes, cockroaches, bees, spiders, scorpions and sea organisms and discuss its relevance in nature. PMID:26103563

  1. Streptococcus pyogenes biofilms—formation, biology, and clinical relevance

    PubMed Central

    Fiedler, Tomas; Köller, Thomas; Kreikemeyer, Bernd

    2015-01-01

    Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options. PMID:25717441

  2. Student perception of relevance of biology content to everyday life: A study in higher education biology courses

    NASA Astrophysics Data System (ADS)

    Himschoot, Agnes Rose

    The purpose of this mixed method case study was to examine the effects of methods of instruction on students' perception of relevance in higher education non-biology majors' courses. Nearly ninety percent of all students in a liberal arts college are required to take a general biology course. It is proposed that for many of those students, this is the last science course they will take for life. General biology courses are suspected of discouraging student interest in biology with large enrollment, didactic instruction, covering a huge amount of content in one semester, and are charged with promoting student disengagement with biology by the end of the course. Previous research has been aimed at increasing student motivation and interest in biology as measured by surveys and test results. Various methods of instruction have been tested and show evidence of improved learning gains. This study focused on students' perception of relevance of biology content to everyday life and the methods of instruction that increase it. A quantitative survey was administered to assess perception of relevance pre and post instruction over three topics typically taught in a general biology course. A second quantitative survey of student experiences during instruction was administered to identify methods of instruction used in the course lecture and lab. While perception of relevance dropped in the study, qualitative focus groups provided insight into the surprising results by identifying topics that are more relevant than the ones chosen for the study, conveying the affects of the instructor's personal and instructional skills on student engagement, explanation of how active engagement during instruction promotes understanding of relevance, the roll of laboratory in promoting students' understanding of relevance as well as identifying external factors that affect student engagement. The study also investigated the extent to which gender affected changes in students' perception of

  3. Biologically relevant neural network architectures for support vector machines.

    PubMed

    Jändel, Magnus

    2014-01-01

    Neural network architectures that implement support vector machines (SVM) are investigated for the purpose of modeling perceptual one-shot learning in biological organisms. A family of SVM algorithms including variants of maximum margin, 1-norm, 2-norm and ν-SVM is considered. SVM training rules adapted for neural computation are derived. It is found that competitive queuing memory (CQM) is ideal for storing and retrieving support vectors. Several different CQM-based neural architectures are examined for each SVM algorithm. Although most of the sixty-four scanned architectures are unconvincing for biological modeling four feasible candidates are found. The seemingly complex learning rule of a full ν-SVM implementation finds a particularly simple and natural implementation in bisymmetric architectures. Since CQM-like neural structures are thought to encode skilled action sequences and bisymmetry is ubiquitous in motor systems it is speculated that trainable pattern recognition in low-level perception has evolved as an internalized motor programme. PMID:24126252

  4. Relevance of ammonium oxidation within biological soil crust communities

    USGS Publications Warehouse

    Johnson, S.L.; Budinoff, C.R.; Belnap, J.; Garcia-Pichel, F.

    2005-01-01

    Thin, vertically structured topsoil communities that become ecologically important in arid regions (biological soil crusts or BSCs) are responsible for much of the nitrogen inputs into pristine arid lands. We studied N2 fixation and ammonium oxidation (AO) at subcentimetre resolution within BSCs from the Colorado Plateau. Pools of dissolved porewater nitrate/ nitrite, ammonium and organic nitrogen in wetted BSCs were high in comparison with those typical of aridosoils. They remained stable during incubations, indicating that input and output processes were of similar magnitude. Areal N2 fixation rates (6.5-48 ??mol C2H2 m-2 h -1) were high, the vertical distribution of N2 fixation peaking close to the surface if populations of heterocystous cyanobacteria were present, but in the subsurface if they were absent. Areal AO rates (19-46 ??mol N m-2 h-1) were commensurate with N2 fixation inputs. When considering oxygen availability, AO activity invariably peaked 2-3 mm deep and was limited by oxygen (not ammonium) supply. Most probable number (MPN)-enumerated ammonia-oxidizing bacteria (6.7-7.9 ?? 103 cells g-1 on average) clearly peaked at 2-3 mm depth. Thus, AO (hence nitrification) is a spatially restricted but important process in the nitrogen cycling of BSC, turning much of the biologically fixed nitrogen into oxidized forms, the fate of which remains to be determined.

  5. What Is the Biological and Clinical Relevance of Fibrin?

    PubMed

    Litvinov, Rustem I; Weisel, John W

    2016-06-01

    As our knowledge of the structure and functions of fibrinogen and fibrin has increased tremendously, several key findings have given some people a superficial impression that the biological and clinical significance of these clotting proteins may be less than earlier thought. Most strikingly, studies of fibrinogen knockout mice demonstrated that many of these mice survive to weaning and beyond, suggesting that fibrin(ogen) may not be entirely necessary. Humans with afibrinogenemia also survive. Furthermore, in recent years, the major emphasis in the treatment of arterial thrombosis has been on inhibition of platelets, rather than fibrin. In contrast to the initially apparent conclusions from these results, it has become increasingly clear that fibrin is essential for hemostasis; is a key factor in thrombosis; and plays an important biological role in infection, inflammation, immunology, and wound healing. In addition, fibrinogen replacement therapy has become a preferred, major treatment for severe bleeding in trauma and surgery. Finally, fibrin is a unique biomaterial and is used as a sealant or glue, a matrix for cells, a scaffold for tissue engineering, and a carrier and/or a vector for targeted drug delivery. PMID:27056152

  6. Student Perception of Relevance of Biology Content to Everyday Life: A Study in Higher Education Biology Courses

    ERIC Educational Resources Information Center

    Himschoot, Agnes Rose

    2012-01-01

    The purpose of this mixed method case study was to examine the effects of methods of instruction on students' perception of relevance in higher education non-biology majors' courses. Nearly ninety percent of all students in a liberal arts college are required to take a general biology course. It is proposed that for many of those students, this is…

  7. Terahertz vibrational properties of water nanoclusters relevant to biology.

    PubMed

    Johnson, Keith

    2012-01-01

    Water nanoclusters are shown from first-principles calculations to possess unique terahertz-frequency vibrational modes in the 1-6 THz range, corresponding to O-O-O "bending," "squashing," and "twisting" "surface" distortions of the clusters. The cluster molecular-orbital LUMOs are huge Rydberg-like "S," "P," "D," and "F" orbitals that accept an extra electron via optical excitation, ionization, or electron donation from interacting biomolecules. Dynamic Jahn-Teller coupling of these "hydrated-electron" orbitals to the THz vibrations promotes such water clusters as vibronically active "structured water" essential to biomolecular function such as protein folding. In biological microtubules, confined water-cluster THz vibrations may induce their "quantum coherence" communicated by Jahn-Teller phonons via coupling of the THz electromagnetic field to the water clusters' large electric dipole moments. PMID:23277672

  8. Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study

    PubMed Central

    Zaborowski, MikoŁaj P.; Balaj, Leonora; Breakefield, Xandra O.; Lai, Charles P.

    2015-01-01

    The release of extracellular vesicles (EVs), including exosomes and microvesicles, is a phenomenon shared by many cell types as a means of communicating with other cells and also potentially removing cell contents. The cargo of EVs includes the proteins, lipids, nucleic acids, and membrane receptors of the cells from which they originate. EVs released into the extracellular space can enter body fluids and potentially reach distant tissues. Once taken up by neighboring and/or distal cells, EVs can transfer functional cargo that may alter the status of recipient cells, thereby contributing to both physiological and pathological processes. In this article, we will focus on EV composition, mechanisms of uptake, and their biological effects on recipient cells. We will also discuss established and recently developed methods used to study EVs, including isolation, quantification, labeling and imaging protocols, as well as RNA analysis. PMID:26955082

  9. Chiral alkynylcarbinols from marine sponges: asymmetric synthesis and biological relevance.

    PubMed

    Listunov, Dymytrii; Maraval, Valérie; Chauvin, Remi; Génisson, Yves

    2015-01-01

    Covering: up to March 2014. Previous review on the topic: B. W. Gung, C. R. Chim., 2009, 12, 489-505. Chiral α-functional lipidic propargylic alcohols extracted from marine sponges, in particular of the pacific genus Petrosia, constitute a class of acetylenic natural products exhibiting remarkable in vitro biological activities, especially anti-tumoral cytotoxicity. These properties, associated to functionalities that are uncommon among natural products, have prompted recent projects on asymmetric total synthesis. On the basis of a three-sector structural typology, three main sub-types of secondary alkynylcarbinols (with either alkyl, alkenyl, or alkynyl as the second substituent) can be identified as the minimal pharmacophoric units. Selected natural products containing these functionalities have been targeted using previously known or on purpose-designed procedures, where the stereo-determining step can be: (i) a C-C bond forming reaction (e.g. the Zn-mediated addition of alkynyl nucleophiles to aldehydes in the presence of chiral aminoalcohols), (ii) a functional layout (e.g. the asymmetric organo- or metallo-catalytic reduction of ynones), or (iii) an enantiomeric resolution (e.g. a lipase-mediated kinetic resolution via acetylation). The promising medicinal importance of these targets is finally surveyed, and future investigation prospects are proposed, such as: (i) further total synthesis of known or future extraction products; (ii) the synthesis of non-natural analogues, with simpler lipophilic environments of the alkynylcarbinol-based pharmacophoric units; (iii) the variation and optimization of both the pharmacophoric units and their lipophilic environment; and (iv) investigations into the biological mode of action of these unique structures. PMID:25275665

  10. Encoding and processing biologically relevant temporal information in electrosensory systems.

    PubMed

    Fortune, E S; Rose, G J; Kawasaki, M

    2006-06-01

    Wave-type weakly electric fish are specialists in time-domain processing: behaviors in these animals are often tightly correlated with the temporal structure of electrosensory signals. Behavioral responses in these fish can be dependent on differences in the temporal structure of electrosensory signals alone. This feature has facilitated the study of temporal codes and processing in central nervous system circuits of these animals. The temporal encoding and mechanisms used to transform temporal codes in the brain have been identified and characterized in several species, including South American gymnotid species and in the African mormyrid genus Gymnarchus. These distantly related groups use similar strategies for neural computations of information on the order of microseconds, milliseconds, and seconds. Here, we describe a suite of mechanisms for behaviorally relevant computations of temporal information that have been elucidated in these systems. These results show the critical role that behavioral experiments continue to have in the study of the neural control of behavior and its evolution. PMID:16450118

  11. IDENTIFICATION OF BIOLOGICALLY RELEVANT GENES USING A DATABASE OF RAT LIVER AND KIDNEY BASELINE GENE EXPRESSION

    EPA Science Inventory

    Microarray data from independent labs and studies can be compared to potentially identify toxicologically and biologically relevant genes. The Baseline Animal Database working group of HESI was formed to assess baseline gene expression from microarray data derived from control or...

  12. FireDB: a compendium of biological and pharmacologically relevant ligands.

    PubMed

    Maietta, Paolo; Lopez, Gonzalo; Carro, Angel; Pingilley, Benjamin J; Leon, Leticia G; Valencia, Alfonso; Tress, Michael L

    2014-01-01

    FireDB (http://firedb.bioinfo.cnio.es) is a curated inventory of catalytic and biologically relevant small ligand-binding residues culled from the protein structures in the Protein Data Bank. Here we present the important new additions since the publication of FireDB in 2007. The database now contains an extensive list of manually curated biologically relevant compounds. Biologically relevant compounds are informative because of their role in protein function, but they are only a small fraction of the entire ligand set. For the remaining ligands, the FireDB provides cross-references to the annotations from publicly available biological, chemical and pharmacological compound databases. FireDB now has external references for 95% of contacting small ligands, making FireDB a more complete database and providing the scientific community with easy access to the pharmacological annotations of PDB ligands. In addition to the manual curation of ligands, FireDB also provides insights into the biological relevance of individual binding sites. Here, biological relevance is calculated from the multiple sequence alignments of related binding sites that are generated from all-against-all comparison of each FireDB binding site. The database can be accessed by RESTful web services and is available for download via MySQL. PMID:24243844

  13. Making Biology Learning Relevant to Students: Integrating People, History, and Context into College Biology Teaching

    ERIC Educational Resources Information Center

    Chamany, Katayoun; Allen, Deborah; Tanner, Kimberly

    2008-01-01

    Teaching students to make connections between what they learn in the classroom and what they see in everyday life is imperative. As biology instructors, they may choose to teach biology devoid of social context, believing that students can make these connections on their own. However, students model their instructors' behaviors, and follow their…

  14. Beyond arousal and valence: The importance of the biological versus social relevance of emotional stimuli

    PubMed Central

    Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

    2012-01-01

    The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention; memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that: a) biologically emotional images hold attention more strongly than socially emotional images, b) memory for biologically emotional images was enhanced even with limited cognitive resources, but c) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images’ subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in visual cortex and greater functional connectivity between amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between amygdala and MPFC than biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity. PMID:21964552

  15. Biological relevance of decamethylcyclopentasiloxane (D5) induced rat uterine endometrial adenocarcinoma tumorigenesis: Mode of action and relevance to humans.

    PubMed

    Klaunig, James E; Dekant, Wolfgang; Plotzke, Kathy; Scialli, Anthony R

    2016-02-01

    Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production and formulation of consumer products with potential exposure to manufacturing workers, consumer, and the general public. Following a combined 2-year inhalation chronic bioassay performed in Fischer 344 (F344) rats, an increase in uterine endometrial adenocarcinomas was noted at the highest concentration to which animals were exposed. No other neoplasms were detected. In this study, a dose of 160 ppm produced an incidence of 8% endometrial adenocarcinomas. Based on a number of experimental studies with D5, the current manuscript examines the biological relevance and possible modes of action for the uterine endometrial adenocarcinomas observed in the rat following chronic exposure to D5. Variable rates of spontaneous uterine endometrial adenocarcinomas have been reported for untreated F344 CrlBr rats. As such, we concluded that the slight increase in uterine endometrial adenocarcinomas observed in the D5 chronic bioassay might not be the result of D5 exposure but may be related to variability of the spontaneous tumor incidence in this strain of rat. However, if the uterine endometrial adenocarcinomas are related to D5-exposure, alteration in the estrous cycle in the aging F344 rat is the most likely mode of action. D5 is not genotoxic or estrogenic. The alteration in the estrous cycle is caused by a decrease in progesterone with an increase in the estrogen:progesterone ratio most likely induced by a decrease in prolactin concentration. Available data support that exposure to D5 influences prolactin concentration. Although the effects on prolactin concentrations in a number of experiments were not always consistent, the available data support the conclusion that D5 is acting via a dopamine receptor agonist-like mechanism to alter the pituitary control of the estrous cycle. In further support of this mode of action, studies in F344 aged animals showed that the effects of D5 on estrous

  16. Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia.

    PubMed

    Key, Brian; Nurcombe, Victor

    2003-01-01

    This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was "student-oriented," ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experiencefirst-hand work in a research laboratory. Our philosophy is a "cradle-to-grave" approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research. PMID:12705657

  17. Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors

    PubMed Central

    Veschi, V; Petroni, M; Bartolazzi, A; Altavista, P; Dominici, C; Capalbo, C; Boldrini, R; Castellano, A; McDowell, H P; Pizer, B; Frati, L; Screpanti, I; Gulino, A; Giannini, G

    2014-01-01

    Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting. PMID:24603328

  18. Population distribution models: species distributions are better modeled using biologically relevant data partitions

    PubMed Central

    2011-01-01

    Background Predicting the geographic distribution of widespread species through modeling is problematic for several reasons including high rates of omission errors. One potential source of error for modeling widespread species is that subspecies and/or races of species are frequently pooled for analyses, which may mask biologically relevant spatial variation within the distribution of a single widespread species. We contrast a presence-only maximum entropy model for the widely distributed oldfield mouse (Peromyscus polionotus) that includes all available presence locations for this species, with two composite maximum entropy models. The composite models either subdivided the total species distribution into four geographic quadrants or by fifteen subspecies to capture spatially relevant variation in P. polionotus distributions. Results Despite high Area Under the ROC Curve (AUC) values for all models, the composite species distribution model of P. polionotus generated from individual subspecies models represented the known distribution of the species much better than did the models produced by partitioning data into geographic quadrants or modeling the whole species as a single unit. Conclusions Because the AUC values failed to describe the differences in the predictability of the three modeling strategies, we suggest using omission curves in addition to AUC values to assess model performance. Dividing the data of a widespread species into biologically relevant partitions greatly increased the performance of our distribution model; therefore, this approach may prove to be quite practical and informative for a wide range of modeling applications. PMID:21929792

  19. Unaffected features of BSA stabilized Ag nanoparticles after storage and reconstitution in biological relevant media.

    PubMed

    Valenti, Laura E; Giacomelli, Carla E

    2015-08-01

    Silver-coated orthopedic implants and silver composite materials have been proposed to produce local biocidal activity at low dose to reduce post-surgery infection that remains one of the major contributions to the patient morbidity. This work presents the synthesis combined with the characterization, colloidal stability in biological relevant media, antimicrobial activity and handling properties of silver nanoparticles (Ag-NP) before and after freeze dry and storage. The nanomaterial was synthesized in aqueous solution with simple, reproducible and low-cost strategies using bovine serum albumin (BSA) as the stabilizing agent. Ag-NP were characterized by means of the size distribution and morphology (UV-vis spectra, dynamic light scattering measurements and TEM images), charge as a function of the pH (zeta potential measurements) and colloidal stability in biological relevant media (UV-vis spectra and dynamic light scattering measurements). Further, the interactions between the protein and Ag-NP were evaluated by surface enhanced Raman spectroscopy (SERS) and the antimicrobial activity was tested with two bacteria strains (namely Staphylococcus aureus and Staphylococcus epidermidis) mainly present in the infections caused by implants and prosthesis in orthopedic surgery. Finally, the Ag-NP dispersed in aqueous solution were dried and stored as long-lasting powders that were easily reconstituted without losing their stability and antimicrobial properties. The proposed methods to stabilize Ag-NP not only produce stable dispersions in media of biological relevance but also long-lasting powders with optimal antimicrobial activity in the nanomolar range. This level is much lower than the cytotoxicity determined in vitro on osteoblasts, osteoclasts and osteoarthritic chondrocytes. The synthesized Ag-NP can be incorporated as additive of biomaterials or pharmaceutical products to confer antimicrobial activity in a powdered form in different formulations, dispersed in

  20. Nuclear Quantum Effects in the Dynamics of Biologically Relevant Systems from First Principles

    NASA Astrophysics Data System (ADS)

    Rossi, Mariana; Fang, Wei; Michaelides, Angelos

    Understanding the structure and dynamics of biomolecules is crucial for unveiling the physics behind biology-related processes. These molecules are very flexible and stabilized by a delicate balance of weak (quantum) interactions, thus requiring the inclusion of anharmonic entropic contributions and an accurate description of the electronic and nuclear structure from quantum mechanics. We here join state of the art density-functional theory (DFT) and path integral molecular dynamics (PIMD) to gain quantitative insight into biologically relevant systems. Our design of a better and more efficient approximation to quantum time correlation functions based on PIMD (TRPMD) enables the calculation of ab initio TCFs with which we calculate IR/vibrational spectra and diffusion coefficients. In stacked polyglutamine strands (structures often related to amyloid diseases) a combination of NQE and H-bond cooperativity provides a small free energy stabilization that we connect to a softening of high frequency modes, enhanced by nuclear quantum anharmonicity [3].

  1. [Microbiological and biological methods of the European Pharmacopoeia. Relevant for each medicinal product].

    PubMed

    Norwig, J

    2014-10-01

    According to the EU Directive 2001/83 the European Pharmacopoeia is the official Pharmacopoeia of the European Union. Therefore the European Pharmacopoeia is one of the legal pharmacopoeial compendia in Germany. Any licensed medicinal product on the German market complies with the requirements of the compendial monographs, if applicable. Because the general monographs of the European Pharmacopoeia on Dosage Forms, Substances for Pharmaceutical Use and Pharmaceutical Preparations refer to the microbiological and biological methods of the Pharmacopoeia, the methods are relevant for medicinal products, too. This article presents a rough summary of the microbiological and biological methods of the European Pharmacopoeia and is intended to be a stimulus for the reader to better understand the original compendia. The short description of the methods mentioned, here, is a summary from the Pharmacopoeia and the non-official collection of comments on the texts of the European Pharmacopoeia. PMID:25200487

  2. KDAC8 substrate specificity quantified by a biologically relevant, label-free deacetylation assay.

    PubMed

    Toro, Tasha B; Watt, Terry J

    2015-12-01

    Analysis of the human proteome has identified thousands of unique protein sequences that contain acetylated lysine residues in vivo. These modifications regulate a variety of biological processes and are reversed by the lysine deacetylase (KDAC) family of enzymes. Despite the known prevalence and importance of acetylation, the details of KDAC substrate recognition are not well understood. While several methods have been developed to monitor protein deacetylation, none are particularly suited for identifying enzyme-substrate pairs of label-free substrates across the entire family of lysine deacetylases. Here, we present a fluorescamine-based assay which is more biologically relevant than existing methods and amenable to probing substrate specificity. Using this assay, we evaluated the activity of KDAC8 and other lysine deacetylases, including a sirtuin, for several peptides derived from known acetylated proteins. KDAC8 showed clear preferences for some peptides over others, indicating that the residues immediately surrounding the acetylated lysine play an important role in substrate specificity. Steady-state kinetics suggest that the sequence surrounding the acetylated lysine affects binding affinity and catalytic rate independently. Our results provide direct evidence that potential KDAC8 substrates previously identified through cell based experiments can be directly deacetylated by KDAC8. Conversely, the data from this assay did not correlate well with predictions from previous screens for KDAC8 substrates using less biologically relevant substrates and assay conditions. Combining results from our assay with mass spectrometry-based experiments and cell-based experiments will allow the identification of specific KDAC-substrate pairs and lead to a better understanding of the biological consequences of these interactions. PMID:26402585

  3. Metal based biologically active compounds: design, synthesis, and antibacterial/antifungal/cytotoxic properties of triazole-derived Schiff bases and their oxovanadium(IV) complexes.

    PubMed

    Chohan, Zahid H; Sumrra, Sajjad H; Youssoufi, Moulay H; Hadda, Taibi B

    2010-07-01

    A new series of oxovanadium(IV) complexes have been designed and synthesized with a new class of triazole Schiff bases derived from the reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde and acetyl pyridine-2-carboxaldehyde, respectively. Physical (magnetic susceptibility, molar conductance), spectral (IR, (1)H NMR, (13)C NMR, mass and electronic) and analytical data have established the structures of these synthesized Schiff bases and their oxovanadium(IV) complexes. The Schiff bases, predominantly act as bidentate and coordinate with the vanadium(IV) metal to give a stoichiometric ratio of 1:2 [M:L], forming a general formulae, [M(L-H)(2)] and [M(L)(2)]SO(4) where L = (L(1))-(L(4)) and M = VO(IV) of these complexes in a square-pyramidal geometry. In order to evaluate the biological activity of Schiff bases and to assess the role of vanadium(IV) metal on biological activity, the triazole Schiff bases and their oxovanadium(IV) complexes have been studied for in vitro antibacterial activity against four Gram-negative (Escherichia coli, Shigella flexenari, Pseudomonas aeruginosa, Salmonella typhi) and two Gram-positive (Staphylococcus aureus, Bacillus subtilis) bacterial strains, in vitro antifungal activity against Trichophyton longifucus, Candida albican, Aspergillus flavus, Microscopum canis, Fusarium solani and Candida glaberata. The simple Schiff bases showed weaker to significant activity against one or more bacterial and fungal strains. In most of the cases higher activity was exhibited upon coordination with vanadium(IV) metal. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina. PMID:20338672

  4. Inactivation of the antibacterial and cytotoxic properties of silver ions by biologically relevant compounds.

    PubMed

    Mulley, Geraldine; Jenkins, A Tobias A; Waterfield, Nicholas R

    2014-01-01

    There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are affected by the assay conditions, particularly the type of growth media used in vitro. The toxicity of Ag+ to bacterial cells is comparable to that of human cells. We demonstrate that biologically relevant compounds such as glutathione, cysteine and human blood components significantly reduce the toxicity of silver ions to clinically relevant pathogenic bacteria and primary human dermal fibroblasts (skin cells). Bacteria are able to grow normally in the presence of silver nitrate at >20-fold the minimum inhibitory concentration (MIC) if Ag+ and thiols are added in a 1:1 ratio because the reaction of Ag+ with extracellular thiols prevents silver ions from interacting with cells. Extracellular thiols and human serum also significantly reduce the antimicrobial activity of silver wound dressings Aquacel-Ag (Convatec) and Acticoat (Smith & Nephew) to Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro. These results have important implications for the deployment of silver as an antimicrobial agent in environments exposed to biological tissue or secretions. Significant amounts of money and effort have been directed at the development of silver-coated medical devices (e.g. dressings, catheters, implants). We believe our findings are essential for the effective design and testing of antimicrobial silver coatings. PMID:24728271

  5. Inactivation of the Antibacterial and Cytotoxic Properties of Silver Ions by Biologically Relevant Compounds

    PubMed Central

    Mulley, Geraldine; Jenkins, A. Tobias A.; Waterfield, Nicholas R.

    2014-01-01

    There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are affected by the assay conditions, particularly the type of growth media used in vitro. The toxicity of Ag+ to bacterial cells is comparable to that of human cells. We demonstrate that biologically relevant compounds such as glutathione, cysteine and human blood components significantly reduce the toxicity of silver ions to clinically relevant pathogenic bacteria and primary human dermal fibroblasts (skin cells). Bacteria are able to grow normally in the presence of silver nitrate at >20-fold the minimum inhibitory concentration (MIC) if Ag+ and thiols are added in a 1∶1 ratio because the reaction of Ag+ with extracellular thiols prevents silver ions from interacting with cells. Extracellular thiols and human serum also significantly reduce the antimicrobial activity of silver wound dressings Aquacel-Ag (Convatec) and Acticoat (Smith & Nephew) to Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro. These results have important implications for the deployment of silver as an antimicrobial agent in environments exposed to biological tissue or secretions. Significant amounts of money and effort have been directed at the development of silver-coated medical devices (e.g. dressings, catheters, implants). We believe our findings are essential for the effective design and testing of antimicrobial silver coatings. PMID:24728271

  6. DNA Hypomethylation Affects Cancer-Related Biological Functions and Genes Relevant in Neuroblastoma Pathogenesis

    PubMed Central

    Mayol, Gemma; Martín-Subero, José I.; Ríos, José; Queiros, Ana; Kulis, Marta; Suñol, Mariona; Esteller, Manel; Gómez, Soledad; Garcia, Idoia; de Torres, Carmen; Rodríguez, Eva; Galván, Patricia; Mora, Jaume; Lavarino, Cinzia

    2012-01-01

    Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Remarkably, such hypomethylation affected cancer-related biological functions and genes relevant to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular, differential methylation in CCND1 affected mostly an evolutionary conserved functionally relevant 3′ untranslated region, suggesting that hypomethylation outside promoter regions may play a role in NB pathogenesis. Hypermethylation targeted genes involved in cell development and proliferation such as RASSF1A, POU2F2 or HOXD3, among others. The results derived from this study provide new candidate epigenetic biomarkers associated with NB as well as insights into the molecular pathogenesis of this tumor, which involves a marked gene-specific hypomethylation. PMID:23144874

  7. Lack of [3H]quinuclidinyl benzylate binding to biologically relevant binding sites on mononuclear cells.

    PubMed

    Adams, E M; Lubrano, T M; Gordon, J; Fields, J Z

    1992-09-01

    We analyzed the binding characteristics of [3H]quinuclidinyl benzylate ([3H]QNB), a muscarinic cholinergic ligand, to rat and human mononuclear cells (MNC). Under various assay conditions, atropine-sensitive, saturable binding occurred with an apparent Kd of 10 nM. Conditions which disrupted the MNC membrane reduced total binding and eliminated specific binding. Muscarinic agonists were unable to inhibit [3H]QNB binding to MNC at concentrations up to 10(-2) M. Stereoisomers dexetimide and levetimide were equipotent inhibitors of binding (IC50 2 x 10(-5) M). We conclude that, although atropine-sensitive binding of [3H]QNB to MNC occurs, the binding is not consistent with the presence of a biologically relevant muscarinic cholinergic receptor. PMID:1392105

  8. Biologically relevant molecular transducer with increased computing power and iterative abilities.

    PubMed

    Ratner, Tamar; Piran, Ron; Jonoska, Natasha; Keinan, Ehud

    2013-05-23

    As computing devices, which process data and interconvert information, transducers can encode new information and use their output for subsequent computing, offering high computational power that may be equivalent to a universal Turing machine. We report on an experimental DNA-based molecular transducer that computes iteratively and produces biologically relevant outputs. As a proof of concept, the transducer accomplished division of numbers by 3. The iterative power was demonstrated by a recursive application on an obtained output. This device reads plasmids as input and processes the information according to a predetermined algorithm, which is represented by molecular software. The device writes new information on the plasmid using hardware that comprises DNA-manipulating enzymes. The computation produces dual output: a quotient, represented by newly encoded DNA, and a remainder, represented by E. coli phenotypes. This device algorithmically manipulates genetic codes. PMID:23706637

  9. Biologically relevant photoacoustic imaging phantoms with tunable optical and acoustic properties.

    PubMed

    Vogt, William C; Jia, Congxian; Wear, Keith A; Garra, Brian S; Joshua Pfefer, T

    2016-10-01

    Established medical imaging technologies such as magnetic resonance imaging and computed tomography rely on well-validated tissue-simulating phantoms for standardized testing of device image quality. The availability of high-quality phantoms for optical-acoustic diagnostics such as photoacoustic tomography (PAT) will facilitate standardization and clinical translation of these emerging approaches. Materials used in prior PAT phantoms do not provide a suitable combination of long-term stability and realistic acoustic and optical properties. Therefore, we have investigated the use of custom polyvinyl chloride plastisol (PVCP) formulations for imaging phantoms and identified a dual-plasticizer approach that provides biologically relevant ranges of relevant properties. Speed of sound and acoustic attenuation were determined over a frequency range of 4 to 9 MHz and optical absorption and scattering over a wavelength range of 400 to 1100 nm. We present characterization of several PVCP formulations, including one designed to mimic breast tissue. This material is used to construct a phantom comprised of an array of cylindrical, hemoglobin-filled inclusions for evaluation of penetration depth. Measurements with a custom near-infrared PAT imager provide quantitative and qualitative comparisons of phantom and tissue images. Results indicate that our PVCP material is uniquely suitable for PAT system image quality evaluation and may provide a practical tool for device validation and intercomparison. PMID:26886681

  10. Enhancement in dentin collagen’s biological stability after proanthocyanidins treatment in clinically relevant time periods

    PubMed Central

    Liu, Yi; Chen, Mingsheng; Yao, Xiaomei; Xu, Changqi; Zhang, Ying; Wang, Yong

    2013-01-01

    Objective To investigate whether proanthocyanidins (PA) is capable of improving dentin collagen’s biological stability through cross-linking within time periods that are clinically relevant. Materials and methods Demineralized dentin collagen slabs were treated with 3.75 wt% PA solution for 10 s, 1 min, 30 min, 60 min, 120 min, 360 min, and 720 min, respectively. The resultant cross-linked collagen samples were subject to digestion with 0.1% collagenase at 37 °C for 2 h, 6 h, 12 h, 24 h, 36 h, and 48 h. The percentage of weight loss after digestion was calculated to evaluate PA-treated collagen’s resistance toward enzymatic degradation. Fourier-Transformed Infrared (FTIR) spectroscopy was used to probe evidences of PA-collagen interactions after various periods of PA treatment. Results The collagenase digestion assay suggests that PA treatment as short as 10 s can enhance collagen’s resistance toward enzymatic challenge. The FTIR spectroscopy further verifies that PA is indeed incorporated into collagen regardless of treatment time, possibly via a mechanism involving the chemical interactions between PA and collagen. Significance This study confirmed that PA can effectively cross-link collagen and improve its biological stability in time periods as short as 10 s. The use of PA as a priming agent is therefore clinically feasible and is a promising approach to improving the durability of current dentin bonding systems. PMID:23434233

  11. Modelling low energy electron and positron tracks in biologically relevant media

    NASA Astrophysics Data System (ADS)

    Blanco, Francisco; Muñoz, Antonio; Almeida, Diogo; Ferreira da Silva, Filipe; Limão-Vieira, Paulo; Fuss, Martina C.; Sanz, Ana G.; García, Gustavo

    2013-09-01

    This colloquium describes an approach to incorporate into radiation damage models the effect of low and intermediate energy (0-100 eV) electrons and positrons, slowing down in biologically relevant materials (water and representative biomolecules). The core of the modelling procedure is a C++ computing programme named “Low Energy Particle Track Simulation (LEPTS)”, which is compatible with available general purpose Monte Carlo packages. Input parameters are carefully selected from theoretical and experimental cross section data and energy loss distribution functions. Data sources used for this purpose are reviewed showing examples of electron and positron cross section and energy loss data for interactions with different media of increasing complexity: atoms, molecules, clusters and condense matter. Finally, we show how such a model can be used to develop an effective dosimetric tool at the molecular level (i.e. nanodosimetry). Recent experimental developments to study the fragmentation induced in biologically material by charge transfer from neutrals and negative ions are also included.

  12. Comparative Analysis of Biologically Relevant Response Curves in Gene Expression Experiments: Heteromorphy, Heterochrony, and Heterometry

    PubMed Central

    Baker, Stuart G.

    2014-01-01

    To gain biological insights, investigators sometimes compare sequences of gene expression measurements under two scenarios (such as two drugs or species). For this situation, we developed an algorithm to fit, identify, and compare biologically relevant response curves in terms of heteromorphy (different curves), heterochrony (different transition times), and heterometry (different magnitudes). The curves are flat, linear, sigmoid, hockey-stick (sigmoid missing a steady state), transient (sigmoid missing two steady states), impulse (with peak or trough), step (with intermediate-level plateau), impulse+ (impulse with an extra parameter), step+ (step with an extra parameter), further characterized by upward or downward trend. To reduce overfitting, we fit the curves to every other response, evaluated the fit in the remaining responses, and identified the most parsimonious curves that yielded a good fit. We measured goodness of fit using a statistic comparable over different genes, namely the square root of the mean squared prediction error as a percentage of the range of responses, which we call the relative prediction error (RPE). We illustrated the algorithm using data on gene expression at 14 times in the embryonic development in two species of frogs. Software written in Mathematica is freely available.

  13. The ChEBI reference database and ontology for biologically relevant chemistry: enhancements for 2013.

    PubMed

    Hastings, Janna; de Matos, Paula; Dekker, Adriano; Ennis, Marcus; Harsha, Bhavana; Kale, Namrata; Muthukrishnan, Venkatesh; Owen, Gareth; Turner, Steve; Williams, Mark; Steinbeck, Christoph

    2013-01-01

    ChEBI (http://www.ebi.ac.uk/chebi) is a database and ontology of chemical entities of biological interest. Over the past few years, ChEBI has continued to grow steadily in content, and has added several new features. In addition to incorporating all user-requested compounds, our annotation efforts have emphasized immunology, natural products and metabolites in many species. All database entries are now 'is_a' classified within the ontology, meaning that all of the chemicals are available to semantic reasoning tools that harness the classification hierarchy. We have completely aligned the ontology with the Open Biomedical Ontologies (OBO) Foundry-recommended upper level Basic Formal Ontology. Furthermore, we have aligned our chemical classification with the classification of chemical-involving processes in the Gene Ontology (GO), and as a result of this effort, the majority of chemical-involving processes in GO are now defined in terms of the ChEBI entities that participate in them. This effort necessitated incorporating many additional biologically relevant compounds. We have incorporated additional data types including reference citations, and the species and component for metabolites. Finally, our website and web services have had several enhancements, most notably the provision of a dynamic new interactive graph-based ontology visualization. PMID:23180789

  14. Design and synthesis of artificial glycopolypeptides as mediators of biologically relevant binding events

    NASA Astrophysics Data System (ADS)

    Polizzotti, Brian D.

    Toxins and pathogens achieve highly efficient and selective binding through multivalent interactions between relevant oligosaccharides and saccharide receptors on each toxin/pathogen subunit. Because of the important role played by protein-carbohydrate interactions in these pathogenic events and in other human diseases, considerable effort has been devoted toward the development of high-affinity ligands for carbohydrate binding proteins. Multivalent ligands synthesized via traditional polymer techniques have provided valuable insight as to the general guidelines that govern these multivalent interactions, but are inherently limited by an inability to effectively control the molecular weight, polydispersity, sequence, and/or geometrical placement of the saccharide moiety on the glycopolymer. This lack of control makes it virtually impossible to determine the origins of increased binding activity. The synthesis of polymers via protein engineering methods allows control over the molecular weight, as well as the number and spacing of saccharides on a scaffold, which permits the structure-based design of polypeptide-based polymers for inhibition of such multivalent binding events. As such, we have employed a combination of protein engineering techniques and chemical methods to produce a family of galactose-functionalized glycopolymers with different backbone compositions and architectures in which the density, saccharide spacing, and linker length of the pendent carbohydrate moieties have been varied. Such ligands may disrupt pathological carbohydrate-mediated recognition and act as a fundamentally new class of noncytotoxic therapeutic agents with broad applicability to a wide range of human disease; in addition, investigations like these will aid in the deconvolution of the impact of multivalency, spacing, and backbone rigidity in a variety of biologically relevant binding events.

  15. Investigation of some biologically relevant redox reactions using electrochemical mass spectrometry interfaced by desorption electrospray ionization

    PubMed Central

    Lu, Mei; Wolff, Chloe; Cui, Weidong

    2013-01-01

    Recently we have shown that, as a versatile ionization technique, desorption electrospray ionization (DESI) can serve as a useful interface to combine electrochemistry (EC) with mass spectrometry (MS). In this study, the EC/DESI-MS method has been further applied to investigate some aqueous phase redox reactions of biological significance, including the reduction of peptide disulfide bonds and nitroaromatics as well as the oxidation of phenothiazines. It was found that knotted/enclosed disulfide bonds in the peptides apamin and endothelin could be electrochemically cleaved. Subsequent tandem MS analysis of the resulting reduced peptide ions using collision-induced dissociation (CID) and electron-capture dissociation (ECD) gave rise to extensive fragment ions, providing a fast protocol for sequencing peptides with complicated disulfide bond linkages. Flunitrazepam and clonazepam, a class of nitroaromatic drugs, are known to undergo reduction into amines which was proposed to involve nitroso and N-hydroxyl intermediates. Now in this study, these corresponding intermediate ions were successfully intercepted and their structures were confirmed by CID. This provides mass spectrometric evidence for the mechanism of the nitro to amine conversion process during nitroreduction, an important redox reaction involved in carcinogenesis. In addition, the well-known oxidation reaction of chlorpromazine was also examined. The putative transient one-electron transfer product, the chlorpromazine radical cation (m/z 318), was captured by MS, for the first time, and its structure was also verified by CID. In addition to these observations, some features of the DESI-interfaced electrochemical mass spectrometry were discussed, such as simple instrumentation and the lack of background signal. These results further demonstrate the feasibility of EC/DESI-MS for the study of the biology-relevant redox chemistry and would find applications in proteomics and drug development research. PMID

  16. Semi-supervised multimodal relevance vector regression improves cognitive performance estimation from imaging and biological biomarkers.

    PubMed

    Cheng, Bo; Zhang, Daoqiang; Chen, Songcan; Kaufer, Daniel I; Shen, Dinggang

    2013-07-01

    Accurate estimation of cognitive scores for patients can help track the progress of neurological diseases. In this paper, we present a novel semi-supervised multimodal relevance vector regression (SM-RVR) method for predicting clinical scores of neurological diseases from multimodal imaging and biological biomarker, to help evaluate pathological stage and predict progression of diseases, e.g., Alzheimer's diseases (AD). Unlike most existing methods, we predict clinical scores from multimodal (imaging and biological) biomarkers, including MRI, FDG-PET, and CSF. Considering that the clinical scores of mild cognitive impairment (MCI) subjects are often less stable compared to those of AD and normal control (NC) subjects due to the heterogeneity of MCI, we use only the multimodal data of MCI subjects, but no corresponding clinical scores, to train a semi-supervised model for enhancing the estimation of clinical scores for AD and NC subjects. We also develop a new strategy for selecting the most informative MCI subjects. We evaluate the performance of our approach on 202 subjects with all three modalities of data (MRI, FDG-PET and CSF) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our SM-RVR method achieves a root-mean-square error (RMSE) of 1.91 and a correlation coefficient (CORR) of 0.80 for estimating the MMSE scores, and also a RMSE of 4.45 and a CORR of 0.78 for estimating the ADAS-Cog scores, demonstrating very promising performances in AD studies. PMID:23504659

  17. Semi-Supervised Multimodal Relevance Vector Regression Improves Cognitive Performance Estimation from Imaging and Biological Biomarkers

    PubMed Central

    Cheng, Bo; Chen, Songcan; Kaufer, Daniel I.

    2013-01-01

    Accurate estimation of cognitive scores for patients can help track the progress of neurological diseases. In this paper, we present a novel semi-supervised multimodal relevance vector regression (SM-RVR) method for predicting clinical scores of neurological diseases from multimodal imaging and biological biomarker, to help evaluate pathological stage and predict progression of diseases, e.g., Alzheimer’s diseases (AD). Unlike most existing methods, we predict clinical scores from multimodal (imaging and biological) biomarkers, including MRI, FDG-PET, and CSF. Considering that the clinical scores of mild cognitive impairment (MCI) subjects are often less stable compared to those of AD and normal control (NC) subjects due to the heterogeneity of MCI, we use only the multimodal data of MCI subjects, but no corresponding clinical scores, to train a semi-supervised model for enhancing the estimation of clinical scores for AD and NC subjects. We also develop a new strategy for selecting the most informative MCI subjects. We evaluate the performance of our approach on 202 subjects with all three modalities of data (MRI, FDG-PET and CSF) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our SM-RVR method achieves a root-mean-square error (RMSE) of 1.91 and a correlation coefficient (CORR) of 0.80 for estimating the MMSE scores, and also a RMSE of 4.45 and a CORR of 0.78 for estimating the ADAS-Cog scores, demonstrating very promising performances in AD studies. PMID:23504659

  18. A Comparison of Biological and Adoptive Mothers and Fathers: The Relevance of Biological Kinship and Gendered Constructs of Parenthood.

    ERIC Educational Resources Information Center

    Miall, Charlene E.; March, Karen

    2003-01-01

    Used qualitative interviews to examine beliefs and values about biological and adoptive parents. Considered how biological kinship, gender, and actual parenting behavior affect the assessments respondents made of the emotional bonding between parents and children. Found that biological and adoptive parents viewed motherhood as instinctive and…

  19. Relevant uses of surface proteins – display on self‐organized biological structures

    PubMed Central

    Jahns, Anika C.; Rehm, Bernd H. A.

    2012-01-01

    Summary Proteins are often found attached to surfaces of self‐assembling biological units such as whole microbial cells or subcellular structures, e.g. intracellular inclusions. In the last two decades surface proteins were identified that could serve as anchors for the display of foreign protein functions. Extensive protein engineering based on structure–function data enabled efficient display of technically and/or medically relevant protein functions. Small size, diversity of the anchor protein as well as support structure, genetic manipulability and controlled cultivation of phages, bacterial cells and yeasts contributed to the establishment of designed and specifically functionalized tools for applications as sensors, catalysis, biomedicine, vaccine development and library‐based screening technologies. Traditionally, phage display is employed for library screening but applications in biomedicine and vaccine development are also perceived. For some diagnostic purposes phages are even too small in size so other carrier materials where needed and gave way for cell and yeast display. Only recently, intracellular inclusions such as magnetosomes, polyhydroxyalkanoate granules and lipid bodies were conceived as stable subcellular structures enabling the display of foreign protein functions and showing potential as specific and tailor‐made devices for medical and biotechnological applications. PMID:21906264

  20. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

    PubMed

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  1. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

    PubMed Central

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  2. Discrimination between biologically relevant calcium phosphate phases by surface-analytical techniques

    NASA Astrophysics Data System (ADS)

    Kleine-Boymann, Matthias; Rohnke, Marcus; Henss, Anja; Peppler, Klaus; Sann, Joachim; Janek, Juergen

    2014-08-01

    The spatially resolved phase identification of biologically relevant calcium phosphate phases (CPPs) in bone tissue is essential for the elucidation of bone remodeling mechanisms and for the diagnosis of bone diseases. Analytical methods with high spatial resolution for the discrimination between chemically quite close phases are rare. Therefore the applicability of state-of-the-art ToF-SIMS, XPS and EDX as chemically specific techniques was investigated. The eight CPPs hydroxyapatite (HAP), β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), octacalcium phosphate (OCP), dicalcium phosphate dihydrate (DCPD), dicalcium phosphate (DCP), monocalcium phosphate (MCP) and amorphous calcium phosphate (ACP) were either commercial materials in high purity or synthesized by ourselves. The phase purity was proven by XRD analysis. All of the eight CPPs show different mass spectra and the phases can be discriminated by applying the principal component analysis method to the mass spectrometric data. The Ca/P ratios of all phosphates were determined by XPS and EDX. With both methods some CPPs can be distinguished, but the obtained Ca/P ratios deviate systematically from their theoretical values. It is necessary in any case to determine a calibration curve, respectively the ZAF values, from appropriate standards. In XPS also the O(1s)-satellite signals are correlated to the CPPs composition. Angle resolved and long-term XPS measurements of HAP clearly prove that there is no phosphate excess at the surface. Decomposition due to X-ray irradiation has not been observed.

  3. Multiple mechanisms for critical behavior in the biologically relevant phase of lecithin bilayers

    NASA Astrophysics Data System (ADS)

    Nagle, John F.; Petrache, Horia I.; Gouliaev, Nikolai; Tristram-Nagle, Stephanie; Liu, Yufeng; Suter, Robert M.; Gawrisch, Klaus

    1998-12-01

    Lipid bilayer membranes manifest critical behavior in the lamellar D spacing observed by x-ray and neutron diffraction as the main phase transition is approached from the biologically relevant high temperature phase. The freezing out of conformational disorder of the hydrocarbon chains drives the main transition, but how this causes critical behavior of D(T) has been an interesting puzzle and various models are under investigation. This paper presents x-ray scattering and NMR data to test the various models. One model involves the straightforward lengthening of hydrocarbon chains as TM is approached, but it is shown that this accounts only for about half the anomalous increase in D. Another model of fluctuation induced expansion of the water region is shown to be inconsistent with two kinds of data. The first inconsistency is the lack of an increase in the Caillé fluctuation parameter η1. The second inconsistency is with D(T) data taken under osmotic pressure. Accurate simulations are employed to predict the theoretical values. A third model considers that the water spacing could expand because other interactions between bilayers may change as TM is approached, but there is no quantitative support for this model at present. A fourth model involving expansion of the headgroup region is tested with NMR data; results are qualitatively consistent but quantitatively inconclusive. While the precise mixture of models is still unresolved, it is concluded that multiple mechanisms must be operating in this critical regime.

  4. Action video game players' visual search advantage extends to biologically relevant stimuli.

    PubMed

    Chisholm, Joseph D; Kingstone, Alan

    2015-07-01

    Research investigating the effects of action video game experience on cognition has demonstrated a host of performance improvements on a variety of basic tasks. Given the prevailing evidence that these benefits result from efficient control of attentional processes, there has been growing interest in using action video games as a general tool to enhance everyday attentional control. However, to date, there is little evidence indicating that the benefits of action video game playing scale up to complex settings with socially meaningful stimuli - one of the fundamental components of our natural environment. The present experiment compared action video game player (AVGP) and non-video game player (NVGP) performance on an oculomotor capture task that presented participants with face stimuli. In addition, the expression of a distractor face was manipulated to assess if action video game experience modulated the effect of emotion. Results indicate that AVGPs experience less oculomotor capture than NVGPs; an effect that was not influenced by the emotional content depicted by distractor faces. It is noteworthy that this AVGP advantage emerged despite participants being unaware that the investigation had to do with video game playing, and participants being equivalent in their motivation and treatment of the task as a game. The results align with the notion that action video game experience is associated with superior attentional and oculomotor control, and provides evidence that these benefits can generalize to more complex and biologically relevant stimuli. PMID:26071923

  5. Development of a biologically relevant calcium phosphate substrate for sum frequency generation vibrational spectroscopy.

    PubMed

    McGall, Sarah J; Davies, Paul B; Neivandt, David J

    2005-10-01

    A novel biologically relevant composite substrate has been prepared consisting of a calcium phosphate (CaP) layer formed by magnetron sputter-coating from a hydroxyapatite (HA) target onto a gold-coated silicon substrate. The CaP layer is intended to mimic tooth and bone surfaces and allows polymers used in oral care to be deposited in a procedure analogous to that used for dental surfaces. The polymer cetyl dimethicone copolyol (CDC) was deposited onto the CaP surface of the substrate by Langmuir Blodgett deposition, and the structure of the adsorbed layer was investigated by the surface specific technique of sum frequency generation (SFG) vibrational spectroscopy. The gold sublayer provides enhancement of the SFG signal arising from the polymer but plays no part in the adsorption of the polymer. The surface morphology of the substrate was investigated using SEM and AFM. The surface roughness was commensurate with that of the thermally evaporated gold sublayer and uniform over areas of at least 36 mum(2). The chemical composition of the CaP-coated surface was determined by FTIR and TOF-SIMS. It was concluded that the surface is primarily calcium phosphate present as a mixture of amorphous, non-hydroxylated phases rather than solely stoichiometric hydroxyapatite. The SFG spectra from CDC on CaP were closely similar, both in resonance wavenumbers and in their relative intensities, with spectra of thin films of CDC recorded directly on gold. Application of previous analysis of the spectra of CDC on gold therefore enabled interpretation of the polymer orientation and conformation on the CaP substrate. PMID:16834276

  6. Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential

    PubMed Central

    Almeida, Mafalda; Costa, Vera L; Costa, Natália R; Ramalho-Carvalho, João; Baptista, Tiago; Ribeiro, Franclim R; Paulo, Paula; Teixeira, Manuel R; Oliveira, Jorge; Lothe, Ragnhild A; Lind, Guro E; Henrique, Rui; Jerónimo, Carmen

    2014-01-01

    Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non-invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of EFEMP1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP1’s role in PCa development. EFEMP1 methylation assay discriminated PCa from normal prostate tissue (NPT; P < 0.001, Kruskall–Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP1 transcription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP1 de novo expression reduces malignant phenotype of PCa cells. EFEMP1 promoter methylation is prevalent in PCa and accurately discriminates PCa from non-cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down-regulation, fostering cell proliferation, invasion and evasion of apoptosis. PMID:25211630

  7. Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble.

    PubMed

    Yongye, Austin B; Bender, Andreas; Martínez-Mayorga, Karina

    2010-08-01

    Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged-RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged-RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 A). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1-4), medium (5-9) and high (10-15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments

  8. Solid-supported cross-metathesis and a formal alkane metathesis for the generation of biologically relevant molecules.

    PubMed

    Méndez, Luciana; Mata, Ernesto G

    2015-02-01

    Solid-phase synthetic strategies toward the generation of libraries of biologically relevant molecules were developed using olefin cross-metathesis as a key step. It is remarkably the formal alkane metathesis based on a one-pot, microwave-assisted, ruthenium-catalyzed cross-metathesis and reduction to obtain Csp3-Csp3 linkages. PMID:25569690

  9. Enhanced stability and local structure in biologically relevant amorphous materials containing pyrophosphate

    SciTech Connect

    Slater, Colin; Laurencin, Danielle; Burnell, Victoria; Smith, Mark E.; Grover, Liam M.; Hriljac, Joseph A.; Wright, Adrian J.

    2012-10-25

    There is increasing evidence that amorphous inorganic materials play a key role in biomineralisation in many organisms, however the inherent instability of synthetic analogues in the absence of the complex in vivo matrix limits their study and clinical exploitation. To address this, we report here an approach that enhances long-term stability to >1 year of biologically relevant amorphous metal phosphates, in the absence of any complex stabilizers, by utilizing pyrophosphates (P{sub 2}O{sub 7}{sup 4-}); species themselves ubiquitous in vivo. Ambient temperature precipitation reactions were employed to synthesise amorphous Ca{sub 2}P{sub 2}O{sub 7}.nH{sub 2}O and Sr{sub 2}P{sub 2}O{sub 7}.nH{sub 2}O (3.8 < n < 4.2) and their stability and structure were investigated. Pair distribution functions (PDF) derived from synchrotron X-ray data indicated a lack of structural order beyond 8 {angstrom} in both phases, with this local order found to resemble crystalline analogues. Further studies, including {sup 1}H and {sup 31}P solid state NMR, suggest the unusually high stability of these purely inorganic amorphous phases is partly due to disorder in the P-O-P bond angles within the P{sub 2}O{sub 7} units, which impede crystallization, and to water molecules, which are involved in H-bonds of various strengths within the structures and hamper the formation of an ordered network. In situ high temperature powder X-ray diffraction data indicated that the amorphous nature of both phases surprisingly persisted to 450 C. Further NMR and TGA studies found that above ambient temperature some water molecules reacted with P{sub 2}O{sub 7} anions, leading to the hydrolysis of some P-O-P linkages and the formation of HPO{sub 4}{sup 2-} anions within the amorphous matrix. The latter anions then recombined into P{sub 2}O{sub 7} ions at higher temperatures prior to crystallization. Together, these findings provide important new materials with unexplored potential for enzyme

  10. "Evo in the News:" Understanding Evolution and Students' Attitudes toward the Relevance of Evolutionary Biology

    ERIC Educational Resources Information Center

    Infanti, Lynn M.; Wiles, Jason R.

    2014-01-01

    This investigation evaluated the effects of exposure to the "Evo in the News" section of the "Understanding Evolution" website on students' attitudes toward biological evolution in undergraduates in a mixed-majors introductory biology course at Syracuse University. Students' attitudes toward evolution and changes therein were…

  11. CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources

    PubMed Central

    Bleda, Marta; Tarraga, Joaquin; de Maria, Alejandro; Salavert, Francisco; Garcia-Alonso, Luz; Celma, Matilde; Martin, Ainoha; Dopazo, Joaquin; Medina, Ignacio

    2012-01-01

    During the past years, the advances in high-throughput technologies have produced an unprecedented growth in the number and size of repositories and databases storing relevant biological data. Today, there is more biological information than ever but, unfortunately, the current status of many of these repositories is far from being optimal. Some of the most common problems are that the information is spread out in many small databases; frequently there are different standards among repositories and some databases are no longer supported or they contain too specific and unconnected information. In addition, data size is increasingly becoming an obstacle when accessing or storing biological data. All these issues make very difficult to extract and integrate information from different sources, to analyze experiments or to access and query this information in a programmatic way. CellBase provides a solution to the growing necessity of integration by easing the access to biological data. CellBase implements a set of RESTful web services that query a centralized database containing the most relevant biological data sources. The database is hosted in our servers and is regularly updated. CellBase documentation can be found at http://docs.bioinfo.cipf.es/projects/cellbase. PMID:22693220

  12. Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless of the Caloric Content or Biological Relevance of the Consumed Stimuli.

    PubMed

    Navarro, Montserrat; Olney, Jeffrey J; Burnham, Nathan W; Mazzone, Christopher M; Lowery-Gionta, Emily G; Pleil, Kristen E; Kash, Thomas L; Thiele, Todd E

    2016-05-01

    It was recently reported that activation of a subset of lateral hypothalamus (LH) GABAergic neurons induced both appetitive (food-seeking) and consummatory (eating) behaviors in vGat-ires-cre mice, while inhibition or deletion of GABAergic neurons blunted these behaviors. As food and caloric-dense liquid solutions were used, the data reported suggest that these LH GABAergic neurons may modulate behaviors that function to maintain homeostatic caloric balance. Here we report that chemogenetic activation of this GABAergic population in vGat-ires-cre mice increased consummatory behavior directed at any available stimulus, including those entailing calories (food, sucrose, and ethanol), those that do not (saccharin and water), and those lacking biological relevance (wood). Chemogenetic inhibition of these neurons attenuated consummatory behaviors. These data indicate that LH GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli. PMID:26442599

  13. Enhanced surface functionality via plasma modification and plasma deposition techniques to create more biologically relevant materials

    NASA Astrophysics Data System (ADS)

    Shearer, Jeffrey C.

    Functionalizing nanoparticles and other unusually shaped substrates to create more biologically relevant materials has become central to a wide range of research programs. One of the primary challenges in this field is creating highly functionalized surfaces without modifying the underlying bulk material. Traditional wet chemistry techniques utilize thin film depositions to functionalize nanomaterials with oxygen and nitrogen containing functional groups, such as --OH and --NHx. These functional groups can serve to create surfaces that are amenable to cell adhesion or can act as reactive groups for further attachment of larger structures, such as macromolecules or antiviral agents. Additional layers, such as SiO2, are often added between the nanomaterial and the functionalized coating to act as a barrier films, adhesion layers, and to increase overall hydrophilicity. However, some wet chemistry techniques can damage the bulk material during processing. This dissertation examines the use of plasma processing as an alternative method for producing these highly functionalized surfaces on nanoparticles and polymeric scaffolds through the use of plasma modification and plasma enhanced chemical vapor deposition techniques. Specifically, this dissertation will focus on (1) plasma deposition of SiO2 barrier films on nanoparticle substrates; (2) surface functionalization of amine and alcohol groups through (a) plasma co-polymerization and (b) plasma modification; and (3) the design and construction of plasma hardware to facilitate plasma processing of nanoparticles and polymeric scaffolds. The body of work presented herein first examines the fabrication of composite nanoparticles by plasma processing. SiOxC y and hexylamine films were coated onto TiO2 nanoparticles to demonstrate enhanced water dispersion properties. Continuous wave and pulsed allyl alcohol plasmas were used to produce highly functionalized Fe2 O3 supported nanoparticles. Specifically, film composition was

  14. Carboxylate-Assisted Iridium-Catalyzed C-H Amination of Arenes with Biologically Relevant Alkyl Azides.

    PubMed

    Zhang, Tao; Hu, Xuejiao; Wang, Zhen; Yang, Tiantian; Sun, Hao; Li, Guigen; Lu, Hongjian

    2016-02-24

    An iridium-catalyzed C-H amination of arenes with a wide substrate scope is reported. Benzamides with electron-donating and -withdrawing groups and linear, branched, and cyclic alkyl azides are all applicable. Cesium carboxylate is crucial for both reactivity and regioselectivity of the reactions. Many biologically relevant molecules, such as amino acid, peptide, steroid, sugar, and thymidine derivatives can be introduced to arenes with high yields and 100 % chiral retention. PMID:26712274

  15. Teleology then and now: the question of Kant's relevance for contemporary controversies over function in biology.

    PubMed

    Zammito, John

    2006-12-01

    'Naturalism' is the aspiration of contemporary philosophy of biology, and Kant simply cannot be refashioned into a naturalist. Instead, epistemological 'deflation' was the decisive feature of Kant's treatment of the 'biomedical' science in his day, so it is not surprising that this might attract some philosophers of science to him today. A certain sense of impasse in the contemporary 'function talk' seems to motivate renewed interest in Kant. Kant--drawing on his eighteenth-century predecessors-provided a discerning and powerful characterization of what biologists had to explain in organic form. His difference from the rest is that he opined that it was impossible to explain it. Its 'inscrutability' was intrinsic. The third Critique essentially proposed the reduction of biology to a kind of pre-scientific descriptivism, doomed never to attain authentic scientificity, to have its 'Newton of the blade of grass'. By contrast, for Locke, and a fortiori for Buffon and his followers, 'intrinsic purposiveness' was a fact of the matter about concrete biological phenomena; the features of internal self-regulation were hypotheses arising out of actual research practice. The difference comes most vividly to light once we recognize Kant's distinction of the concept of organism from the concept of life. If biology must conceptualize self-organization as actual in the world, Kant's regulative/constitutive distinction is pointless in practice and the (naturalist) philosophy of biology has urgent work to undertake for which Kant turns out not to be very helpful. PMID:17157770

  16. COMPARISON OF QUANTUM MECHANICAL METHODS TO COMPUTE THE BIOLOGICALLY RELEVANT REACTIVITIES OF CYCLOPENTA POLYCYCLIC AROMATIC HYDROCARBONS

    EPA Science Inventory

    In computational studies to understand the interaction of polycyclic aromatic hydrocarbons (PAHS) with biomolecular systems, the semi-empirical method AM1 has been used to determine the geometry of the PAH, its metabolites and relevant intermediates. umber of studies have shown t...

  17. Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments (Final Report)

    EPA Science Inventory

    This technical paper provides defensible approximations for what the depth of the biologically active zone, or “biotic zone” is within certain environments. The methods used in this study differ somewhat between Part 1 (Terrestrial Biotic Zone) and Part 2 (Aquatic Biotic Zone). ...

  18. Soluble Epidermal Growth Factor Receptors (sEGFRs) in Cancer: Biological Aspects and Clinical Relevance

    PubMed Central

    Maramotti, Sally; Paci, Massimiliano; Manzotti, Gloria; Rapicetta, Cristian; Gugnoni, Mila; Galeone, Carla; Cesario, Alfredo; Lococo, Filippo

    2016-01-01

    The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers. But what are the origins of circulating sGFRs? Are they naturally occurring molecules or tumor-derived products? Among these, the epidermal growth factor receptor (EGFR) is a cell-surface molecule significantly involved in cancer development and progression; it can be processed into biological active soluble isoforms (sEGFR). We have carried out an extensive review of the currently available literature on the sEGFRs and their mechanisms of regulation and biological function, with the intent to clarify the role of these molecules in cancer (and other pathological conditions) and, on the basis of the retrieved evidences, speculate about their potential use in the clinical setting. PMID:27104520

  19. Soluble Epidermal Growth Factor Receptors (sEGFRs) in Cancer: Biological Aspects and Clinical Relevance.

    PubMed

    Maramotti, Sally; Paci, Massimiliano; Manzotti, Gloria; Rapicetta, Cristian; Gugnoni, Mila; Galeone, Carla; Cesario, Alfredo; Lococo, Filippo

    2016-01-01

    The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers. But what are the origins of circulating sGFRs? Are they naturally occurring molecules or tumor-derived products? Among these, the epidermal growth factor receptor (EGFR) is a cell-surface molecule significantly involved in cancer development and progression; it can be processed into biological active soluble isoforms (sEGFR). We have carried out an extensive review of the currently available literature on the sEGFRs and their mechanisms of regulation and biological function, with the intent to clarify the role of these molecules in cancer (and other pathological conditions) and, on the basis of the retrieved evidences, speculate about their potential use in the clinical setting. PMID:27104520

  20. Biologically relevant oxidants cause bound proteins to readily oxidatively cross-link at Guanine.

    PubMed

    Solivio, Morwena J; Nemera, Dessalegn B; Sallans, Larry; Merino, Edward J

    2012-02-20

    Oxidative DNA-protein cross-links have received less attention than other types of DNA damage and remain as one of the least understood types of oxidative lesion. A model system using ribonuclease A and a 27-nucleotide DNA was used to determine the propensity of oxidative cross-linking to occur in the presence of oxidants. Cross-link formation was examined using four different oxidation systems that generate singlet oxygen, superoxide, and metal-based Fenton reactions. It is shown that oxidative cross-linking occurs in yields ranging from 14% to a maximal yield of 61% in all oxidative systems when equivalent concentrations of DNA and protein are present. Because singlet oxygen is the most efficient oxidation system in generating DNA-protein cross-links, it was chosen for further analyses. Cross-linking occurred with single-stranded DNA binding protein and not with bovine serum albumin. Addition of salt lowered nonspecific binding affinity and lowered cross-link yield by up to 59%. The yield of cross-linking increased with increased ratios of protein compared with DNA. Cross-linking was highly dependent on the number of guanines in a DNA sequence. Loss of guanine content on the 27-nucleotide DNA led to nearly complete loss in cross-linking, while primer extension studies showed cross-links to predominantly occur at guanine base on a 100-nucleotide DNA. The chemical species generated were examined using two peptides derived from the ribonuclease A sequence, N-acetyl-AAAKF and N-acetyl-AYKTT, which were cross-linked to 2'-deoxyguanosine. The cross-link products were spiroiminodihydantoin, guanidinohydantoin, and tyrosyl-based adducts. Formation of tyrosine-based adducts may be competitive with the more well-studied lysine-based cross-links. We conclude that oxidative cross-links may be present at high levels in cells since the propensity to oxidatively cross-link is high and so much of the genomic DNA is coated with protein. PMID:22216745

  1. multiClust: An R-package for Identifying Biologically Relevant Clusters in Cancer Transcriptome Profiles

    PubMed Central

    Lawlor, Nathan; Fabbri, Alec; Guan, Peiyong; George, Joshy; Karuturi, R. Krishna Murthy

    2016-01-01

    Clustering is carried out to identify patterns in transcriptomics profiles to determine clinically relevant subgroups of patients. Feature (gene) selection is a critical and an integral part of the process. Currently, there are many feature selection and clustering methods to identify the relevant genes and perform clustering of samples. However, choosing an appropriate methodology is difficult. In addition, extensive feature selection methods have not been supported by the available packages. Hence, we developed an integrative R-package called multiClust that allows researchers to experiment with the choice of combination of methods for gene selection and clustering with ease. Using multiClust, we identified the best performing clustering methodology in the context of clinical outcome. Our observations demonstrate that simple methods such as variance-based ranking perform well on the majority of data sets, provided that the appropriate number of genes is selected. However, different gene ranking and selection methods remain relevant as no methodology works for all studies. PMID:27330269

  2. Biologically Relevant Mechanism For Catalytic Removal of Superoxide by Simple Manganese Compounds

    SciTech Connect

    Barnese K.; Cabelli D.; Gralla, E.B.; Valentine, J.S.

    2012-05-01

    Nonenzymatic manganese was first shown to provide protection against superoxide toxicity in vivo in 1981, but the chemical mechanism responsible for this protection subsequently became controversial due to conflicting reports concerning the ability of Mn to catalyze superoxide disproportionation in vitro. In a recent communication, we reported that low concentrations of a simple Mn phosphate salt under physiologically relevant conditions will indeed catalyze superoxide disproportionation in vitro. We report now that two of the four Mn complexes that are expected to be most abundant in vivo, Mn phosphate and Mn carbonate, can catalyze superoxide disproportionation at physiologically relevant concentrations and pH, whereas Mn pyrophosphate and citrate complexes cannot. Additionally, the chemical mechanisms of these reactions have been studied in detail, and the rates of reactions of the catalytic removal of superoxide by Mn phosphate and carbonate have been modeled. Physiologically relevant concentrations of these compounds were found to be sufficient to mimic an effective concentration of enzymatic superoxide dismutase found in vivo. This mechanism provides a likely explanation as to how Mn combats superoxide stress in cellular systems.

  3. Relevance of Crop Biology for Environmental Risk Assessment of Genetically Modified Crops in Africa.

    PubMed

    Akinbo, Olalekan; Hancock, James F; Makinde, Diran

    2015-01-01

    Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERAs). This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for ERA include growth habit, center of origin, center of genetic diversity, proximity of wild relatives, inter-fertility, mode of pollen dispersal, length of pollen viability, mating system, invasiveness, weediness, mode of propagation, mode of seed dispersal, and length of seed dormancy. In this paper, we discuss the crops being genetic engineered in Africa and describe the crop biology of those with native relatives. PMID:26501055

  4. Relevance of Crop Biology for Environmental Risk Assessment of Genetically Modified Crops in Africa

    PubMed Central

    Akinbo, Olalekan; Hancock, James F.; Makinde, Diran

    2015-01-01

    Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERAs). This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for ERA include growth habit, center of origin, center of genetic diversity, proximity of wild relatives, inter-fertility, mode of pollen dispersal, length of pollen viability, mating system, invasiveness, weediness, mode of propagation, mode of seed dispersal, and length of seed dormancy. In this paper, we discuss the crops being genetic engineered in Africa and describe the crop biology of those with native relatives. PMID:26501055

  5. Inorganic concepts relevant to metal binding, activity, and toxicity in a biological system

    SciTech Connect

    Hoeschele, J.D. . Parke-Davis Pharmaceutical Research Div.); Turner, J.E.; England, M.W. )

    1990-01-01

    The purpose of this paper is to review selected physical and inorganic concepts and factors which might be important in assessing and/or understanding the fact and disposition of a metal system in a biological environment. Hopefully, such inquiries will ultimately permit us to understand, rationalize, and predict differences and trends in biological effects as a function of the basic nature of a metal system and, in optimal cases, serve as input to a system of guidelines for the notion of Chemical Dosimetry.'' The plan of this paper is to first review, in general terms, the basic principles of the Crystal Field Theory (CFT), a unifying theory of bonding in metal complexes. This will provide the necessary theoretical background for the subsequent discussion of selected concepts and factors. 21 refs., 7 figs., 6 tabs.

  6. Consistent Robustness Analysis (CRA) Identifies Biologically Relevant Properties of Regulatory Network Models

    PubMed Central

    Saithong, Treenut; Painter, Kevin J.; Millar, Andrew J.

    2010-01-01

    Background A number of studies have previously demonstrated that “goodness of fit” is insufficient in reliably classifying the credibility of a biological model. Robustness and/or sensitivity analysis is commonly employed as a secondary method for evaluating the suitability of a particular model. The results of such analyses invariably depend on the particular parameter set tested, yet many parameter values for biological models are uncertain. Results Here, we propose a novel robustness analysis that aims to determine the “common robustness” of the model with multiple, biologically plausible parameter sets, rather than the local robustness for a particular parameter set. Our method is applied to two published models of the Arabidopsis circadian clock (the one-loop [1] and two-loop [2] models). The results reinforce current findings suggesting the greater reliability of the two-loop model and pinpoint the crucial role of TOC1 in the circadian network. Conclusions Consistent Robustness Analysis can indicate both the relative plausibility of different models and also the critical components and processes controlling each model. PMID:21179566

  7. The relevance and potential roles of microphysiological systems in biology and medicine

    PubMed Central

    Wikswo, John P.

    2014-01-01

    Microphysiological systems (MPS), consisting of interacting organs-on-chips or tissue-engineered, 3D organ constructs that use human cells, present an opportunity to bring new tools to biology, medicine, pharmacology, physiology, and toxicology. This issue of Experimental Biology and Medicine describes the ongoing development of MPS that can serve as in vitro models for bone and cartilage, brain, gastrointestinal tract, lung, liver, microvasculature, reproductive tract, skeletal muscle, and skin. Related topics addressed here are the interconnection of organs-on-chips to support physiologically based pharmacokinetics and drug discovery and screening, and the microscale technologies that regulate stem cell differentiation. The initial motivation for creating MPS was to increase the speed, efficiency, and safety of pharmaceutical development and testing, paying particular regard to the fact that neither monolayer monocultures of immortal or primary cell lines nor animal studies can adequately recapitulate the dynamics of drug-organ, drug-drug, and drug-organ-organ interactions in humans. Other applications include studies of the effect of environmental toxins on humans, identification, characterization, and neutralization of chemical and biological weapons, controlled studies of the microbiome and infectious disease that cannot be conducted in humans, controlled differentiation of induced pluripotent stem cells into specific adult cellular phenotypes, and studies of the dynamics of metabolism and signaling within and between human organs. The technical challenges are being addressed by many investigators, and in the process, it seems highly likely that significant progress will be made toward providing more physiologically realistic alternatives to monolayer monocultures or whole animal studies. The effectiveness of this effort will be determined in part by how easy the constructs are to use, how well they function, how accurately they recapitulate and report human

  8. Biologically relevant 3D tumor arrays: treatment response and the importance of stromal partners

    NASA Astrophysics Data System (ADS)

    Rizvi, Imran; Celli, Jonathan P.; Xu, Feng; Evans, Conor L.; Abu-Yousif, Adnan O.; Muzikansky, Alona; Elrington, Stefan A.; Pogue, Brian W.; Finkelstein, Dianne M.; Demirci, Utkan; Hasan, Tayyaba

    2011-02-01

    The development and translational potential of therapeutic strategies for cancer is limited, in part, by a lack of biological models that capture important aspects of tumor growth and treatment response. It is also becoming increasingly evident that no single treatment will be curative for this complex disease. Rationally-designed combination regimens that impact multiple targets provide the best hope of significantly improving clinical outcomes for cancer patients. Rapidly identifying treatments that cooperatively enhance treatment efficacy from the vast library of candidate interventions is not feasible, however, with current systems. There is a vital, unmet need to create cell-based research platforms that more accurately mimic the complex biology of human tumors than monolayer cultures, while providing the ability to screen therapeutic combinations more rapidly than animal models. We have developed a highly reproducible in vitro three-dimensional (3D) tumor model for micrometastatic ovarian cancer (OvCa), which in conjunction with quantitative image analysis routines to batch-process large datasets, serves as a high throughput reporter to screen rationally-designed combination regimens. We use this system to assess mechanism-based combination regimens with photodynamic therapy (PDT), which sensitizes OvCa to chemo and biologic agents, and has shown promise in clinic trials. We show that PDT synergistically enhances carboplatin efficacy in a sequence dependent manner. In printed heterocellular cultures we demonstrate that proximity of fibroblasts enhances 3D tumor growth and investigate co-cultures with endothelial cells. The principles described here could inform the design and evaluation of mechanism-based therapeutic options for a broad spectrum of metastatic solid tumors.

  9. Solid State Structures of Alkali Metal Ion Complexes Formed by Low-Molecular-Weight Ligands of Biological Relevance.

    PubMed

    Aoki, Katsuyuki; Murayama, Kazutaka; Hu, Ning-Hai

    2016-01-01

    This chapter provides structural data, mainly metal binding sites/modes, observed in crystal structures of alkali metal ion complexes containing low-molecular-weight ligands of biological relevance, mostly obtained from the Cambridge Structural Database (the CSD version 5.35 updated to February 2014). These ligands include (i) amino acids and small peptides, (ii) nucleic acid constituents (excluding quadruplexes and other oligonucleotides), (iii) simple carbohydrates, and (iv) naturally occurring antibiotic ionophores. For some representative complexes of these ligands, some details on the environment of the metal coordination and structural characteristics are described. PMID:26860299

  10. [Biological agents in animal breeding: an ancient but still relevant risk].

    PubMed

    Vellere, F; Cucchi, I; Somaruga, C; Brambilla, G; Colosio, C

    2012-01-01

    Agricultural activities expose workers to biological risk, due to the close contact that could occur with pathogens' reservoirs, such as soil, animals, manure and animal products. The paper describes factors that have contributed on the reduction or eradication of zoonoses, such as brucellosis, salmonellosis and bovine tuberculosis (monitoring and prevention of animal infectious diseases, industrialization and mechanization of agricultural activities), and on the other hand the emergence of new risks and new diseases (adaptability of microorganisms, generation of new strains, antibiotic resistance, dissemination of vectors). The role of Occupational Medicine in the prevention of zoonoses is discussed. PMID:23405674

  11. The relevance of nanoscale biological fragments for ice nucleation in clouds

    PubMed Central

    O′Sullivan, D.; Murray, B. J.; Ross, J. F.; Whale, T. F.; Price, H. C.; Atkinson, J. D.; Umo, N. S.; Webb, M. E.

    2015-01-01

    Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles. PMID:25626414

  12. What Is Stochastic Resonance? Definitions, Misconceptions, Debates, and Its Relevance to Biology

    PubMed Central

    McDonnell, Mark D.; Abbott, Derek

    2009-01-01

    Stochastic resonance is said to be observed when increases in levels of unpredictable fluctuations—e.g., random noise—cause an increase in a metric of the quality of signal transmission or detection performance, rather than a decrease. This counterintuitive effect relies on system nonlinearities and on some parameter ranges being “suboptimal”. Stochastic resonance has been observed, quantified, and described in a plethora of physical and biological systems, including neurons. Being a topic of widespread multidisciplinary interest, the definition of stochastic resonance has evolved significantly over the last decade or so, leading to a number of debates, misunderstandings, and controversies. Perhaps the most important debate is whether the brain has evolved to utilize random noise in vivo, as part of the “neural code”. Surprisingly, this debate has been for the most part ignored by neuroscientists, despite much indirect evidence of a positive role for noise in the brain. We explore some of the reasons for this and argue why it would be more surprising if the brain did not exploit randomness provided by noise—via stochastic resonance or otherwise—than if it did. We also challenge neuroscientists and biologists, both computational and experimental, to embrace a very broad definition of stochastic resonance in terms of signal-processing “noise benefits”, and to devise experiments aimed at verifying that random variability can play a functional role in the brain, nervous system, or other areas of biology. PMID:19562010

  13. The relevance of nanoscale biological fragments for ice nucleation in clouds

    NASA Astrophysics Data System (ADS)

    O‧Sullivan, D.; Murray, B. J.; Ross, J. F.; Whale, T. F.; Price, H. C.; Atkinson, J. D.; Umo, N. S.; Webb, M. E.

    2015-01-01

    Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles.

  14. Advances in clarifying the phylogenetic relationships of acacias: Relevance for biological control

    NASA Astrophysics Data System (ADS)

    Kleinjan, C. A.; Hoffmann, J. H.

    2013-04-01

    Biological control of invasive Australian acacias will benefit from recent advances in resolving the phylogenetic relationships of Acacia s.l. and Acacia s.s. ("Australian acacias") within the subfamily Mimosoideae. Some of the phytophage taxa associated with Acacia s.s. display fidelity to a derived clade within the genus. This derived clade contains most of the Acacia s.s. species that have become problematic around the world. Phytophages that are demonstrably restricted to species within the derived clade pose essentially no risk to species outside Acacia s.s.. In contrast, prospective agents able to develop on species in the basal lineages of Acacia s.s. would require more-expansive testing because Acacia s.s. is closely related to the Ingeae, and then sequentially to the genera Acaciella, Mariosousa and Senegalia. Importantly, Vachellia is distantly related to Acacia s.s., being nested in basal Mimoseae lineages, and is thus less likely to be at risk than previously envisaged. Elucidation of these trends shows the benefits of having a comprehensive knowledge of the phylogeny of plants and phytophages under consideration for biological control.

  15. Mammary Carcinogen-Protein Binding Potentials: Novel and Biologically Relevant Structure-Activity Relationship Model Descriptors

    PubMed Central

    Cunningham, A.R.; Qamar, S.; Carrasquer, C.A.; Holt, P.A.; Maguire, J.M.; Cunningham, S.L.; Trent, J.O.

    2010-01-01

    Previously, SAR models for carcinogenesis used descriptors that are essentially chemical descriptors. Herein we report the development of models with the cat-SAR expert system using biological descriptors (i.e., ligand-receptor interactions) rat mammary carcinogens. These new descriptors are derived from the virtual screening for ligand-receptor interactions of carcinogens, non-carcinogens, and mammary carcinogens to a set of 5494 target proteins. Leave-one-out validations of the ligand mammary carcinogen non-carcinogen model had a concordance between experimental and predicted results of 71% and the mammary carcinogen non-mammary carcinogen model was 72% concordant. The development of a hybrid fragment-ligand model improved the concordances to 85 and 83%, respectively. In a separate external validation exercise, hybrid fragment-ligand models had concordances of 81 and 76%. Analyses of example rat mammary carcinogens including the food mutagen and estrogenic compound PhIP, the herbicide atrazine, and the drug indomethacin, the ligand model identified a number of proteins associated with each compound that had previously been referenced in Medline in conjunction with the test chemical and separately with association to breast cancer. This new modelling approach can enhance model predictivity and help bridge the gap between chemical structure and carcinogenic activity by descriptors that are related to biological targets. PMID:20818582

  16. Recent advances in superhydrophobic surfaces and their relevance to biology and medicine.

    PubMed

    Ciasca, G; Papi, M; Businaro, L; Campi, G; Ortolani, M; Palmieri, V; Cedola, A; De Ninno, A; Gerardino, A; Maulucci, G; De Spirito, M

    2016-02-01

    By mimicking naturally occurring superhydrophobic surfaces, scientists can now realize artificial surfaces on which droplets of a few microliters of water are forced to assume an almost spherical shape and an extremely high contact angle. In recent decades, these surfaces have attracted much attention due to their technological applications for anti-wetting and self-cleaning materials. Very recently, researchers have shifted their interest to investigate whether superhydrophobic surfaces can be exploited to study biological systems. This research effort has stimulated the design and realization of new devices that allow us to actively organize, visualize and manipulate matter at both the microscale and nanoscale levels. Such precise control opens up wide applications in biomedicine, as it allows us to directly manipulate objects at the typical length scale of cells and macromolecules. This progress report focuses on recent biological and medical applications of superhydrophobicity. Particular regard is paid to those applications that involve the detection, manipulation and study of extremely small quantities of molecules, and to those that allow high throughput cell and biomaterial screening. PMID:26844980

  17. Collisions between low-energy electrons and small polyatomic targets of biological relevance

    NASA Astrophysics Data System (ADS)

    Hargreaves, Leigh

    2016-05-01

    Over the last decade, cross section measurements and calculations for DNA prototype molecules have received significant attention from the collisions community, due to the potential applications of this data in modelling electron transport through biological matter with a view to improving radiation dosimetry. Such data are additionally interesting from a fundamental aspect, as small carbon-based molecules are ideal targets for considering effects including target conformation, long-range dynamical interactions and coupling effects between the various degrees of freedom on the scattering properties of the target. At the California State University Fullerton, we have made a series of measurements of the elastic, vibrationally inelastic and electronically inelastic cross sections for a variety of small polyatomic targets, including water and the basic alcohols, ethylene, toluene and several fluorinated alkanes. These processes are important in a range of applications, primarily for modelling electron transport and thermalization, and energy deposition to a biological media. The data were obtained using a high resolution electron energy-loss spectrometer, operating in a crossed beam configuration with a moveable aperture gas source. The gas source design facilitates both an expedient and highly accurate method of removing background signal, and removes uncertainties from the data due to uncertainties in the beam profile. We have also performed scattering calculations employing the Schwinger Multichannel method, in collaboration with the California institute of technology, to compare with our measurements. In this talk, I will present an overview of our recent data and future research plans.

  18. Rapid generation of biologically relevant hydrogels containing long-range chemical gradients **

    PubMed Central

    He, Jiankang; Du, Yanan; Villa-Uribe, Jose L; Hwang, Changmo; Li, Dichen

    2010-01-01

    Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue-mimetic constructs. Here we describe a simple and versatile method to rapidly generate materials containing centimeter-long gradients of chemical properties in a microfluidic channel. The formation of chemical gradient was initiated by a passive-pump-induced forward flow and further developed during an evaporation-induced backward flow. The gradient was spatially controlled by the backward flow time and the hydrogel material containing the gradient was synthesized via photopolymerization. Gradients of a cell-adhesion ligand, Arg-Gly-Asp-Ser (RGDS), was incorporated in the poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels to test the response of endothelial cells. The cells attached and spread along the hydrogel material in a manner consistent with the RGDS gradient profile. A hydrogel containing PEG-DA concentration gradient and constant RGDS concentration was also generated. The morphology of cells cultured on such hydrogel changed from round in the lower PEG-DA concentration regions to well-spread in the higher PEG-DA concentration regions. This approach is expected to be a valuable tool to investigate the cell-material interactions in a simple and high-throughput manner and to design graded biomimetic materials for tissue engineering applications. PMID:20216924

  19. Catch bonds: physical models, structural bases, biological function and rheological relevance.

    PubMed

    Zhu, Cheng; Lou, Jizhong; McEver, Rodger P

    2005-01-01

    Force can shorten the lifetimes of macromolecular complexes (e.g., 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, possible structural bases, their relation to flow-enhanced adhesion, and the potential biorheological relevance. PMID:16369083

  20. New Insights on the Biophysical Interaction of Resveratrol with Biomembrane Models: Relevance for Its Biological Effects.

    PubMed

    Neves, Ana Rute; Nunes, Cláudia; Reis, Salette

    2015-09-01

    Resveratrol has been widely studied because of its pleiotropic effects in cancer therapy, neuroprotection, and cardioprotection. It is believed that the interaction of resveratrol with biological membranes may play a key role in its therapeutic activity. The capacity of resveratrol to partition into lipid bilayers, its possible location within the membrane, and the influence of this compound on the membrane fluidity were investigated using membrane mimetic systems composed of egg l-α-phosphatidylcholine (EPC), cholesterol (CHOL), and sphingomyelin (SM). The results showed that resveratrol has greater affinity for the EPC bilayers than for EPC:CHOL [4:1] and EPC:CHOL:SM [1:1:1] membrane models. The increased difficulty in penetrating tight packed membranes is also demonstrated by fluorescence quenching of probes and by fluorescence anisotropy measurements. Resveratrol may be involved in the regulation of cell membrane fluidity, thereby contributing for cell homeostasis. PMID:26237152

  1. Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations

    PubMed Central

    Lynch, Maureen; Fischbach, Claudia

    2014-01-01

    Bone metastasis represents the leading cause of breast cancer related-deaths. However, the effect of skeleton-associated biomechanical signals on the initiation, progression, and therapy response of breast cancer bone metastasis is largely unknown. This review seeks to highlight possible functional connections between skeletal mechanical signals and breast cancer bone metastasis and their contribution to clinical outcome. It provides an introduction to the physical and biological signals underlying bone functional adaptation and discusses the modulatory roles of mechanical loading and breast cancer metastasis in this process. Following a definition of biophysical design criteria, in vitro and in vivo approaches from the fields of bone biomechanics and tissue engineering will be reviewed that may be suitable to investigate breast cancer bone metastasis as a function of varied mechano-signaling. Finally, an outlook of future opportunities and challenges associated with this newly emerging field will be provided. PMID:25174311

  2. Solid state structures of cadmium complexes with relevance for biological systems.

    PubMed

    Carballo, Rosa; Castiñeiras, Alfonso; Domínguez-Martín, Alicia; García-Santos, Isabel; Niclós-Gutiérrez, Juan

    2013-01-01

    This chapter provides a review of the literature on structural information from crystal structures determined by X-ray diffractometry of cadmium(II) complexes containing ligands of potential biological interest. These ligands fall into three broad classes, (i) those containing N-donors such as purine or pyrimidine bases and derivatives of adenine, guanine or cytosine, (ii) those containing carboxylate groups such as α-amino acids, in particular the twenty essential ones, the water soluble vitamins (B-complex) or the polycarboxylates of EDTA type ligands, and (iii) S-donors such as thiols/thiolates or dithiocarbamates. A crystal and molecular structural analysis has been carried out for some representative complexes of these ligands, specifically addressing the coordination mode of ligands, the coordination environment of cadmium and, in some significant cases, the intermolecular interactions. PMID:23430774

  3. Biological relevance of oxidative debris present in as-prepared graphene oxide

    PubMed Central

    Pattammattel, Ajith; Williams, Christina L.; Pande, Paritosh; Tsui, William G.; Basu, Ashis K.

    2015-01-01

    The influence of oxidative debris (OD) present in as-prepared graphene oxide (GO) suspensions on proteins and its toxicity to human embryonic kidney cells (HEK-293T) are reported here. The OD was removed by repeated washing with aqueous ammonia to produce the corresponding base-washed GO (bwGO). The loading (w/w) of bovine serum albumin (BSA) was increased by 85% after base washing, whereas the loading of hemoglobin (Hb) and lysozyme (Lyz), respectively, was decreased by 160% and 100%. The secondary structures of 13 different proteins bound to bwGO were compared with the corresponding proteins bound to GO using the UV circular dichroism spectroscopy. There was a consistent loss of protein secondary structure with bwGO when compared with proteins bound to GO, but no correlation between either the isoelectric point or hydrophobicity of the protein and the extent of structure loss was observed. All enzymes bound to bwGO and GO indicated significant activities, and a strong correlation between the enzymatic activity and the extent of structure retention was noted, regardless of the presence or absence of OD. At low loadings (<100 μg/mL) both GO and bwGO showed excellent cell viability but substantial cytotoxicity (~40% cell death) was observed at high loadings (>100 μg/mL). In control studies, OD by itself did not alter the growth rate even after a 48-h incubation. Thus, the presence of OD in GO played a very important role in controlling the chemical and biological nature of the protein-GO interface and the presence of OD in GO improved its biological compatibility when compared to bwGO. PMID:26257893

  4. Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection.

    PubMed

    Pan, Tianhong; Xie, Wenjie; Jankovic, Joseph; Le, Weidong

    2005-03-29

    Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson's disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10 microM significantly increased DAT mRNA levels by 54-130% in 4-8 h, VMAT2 mRNA levels by 34% in 4 h, and Nurr1 mRNA levels by 31-39% in 2-4 h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2 h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA receptor antagonist, didn't show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D3 DA receptor. PMID:15740846

  5. TaBoo SeArch Algorithm with a Modified Inverse Histogram for Reproducing Biologically Relevant Rare Events of Proteins.

    PubMed

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2016-05-10

    The TaBoo SeArch (TBSA) algorithm [ Harada et al. J. Comput. Chem. 2015 , 36 , 763 - 772 and Harada et al. Chem. Phys. Lett. 2015 , 630 , 68 - 75 ] was recently proposed as an enhanced conformational sampling method for reproducing biologically relevant rare events of a given protein. In TBSA, an inverse histogram of the original distribution, mapped onto a set of reaction coordinates, is constructed from trajectories obtained by multiple short-time molecular dynamics (MD) simulations. Rarely occurring states of a given protein are statistically selected as new initial states based on the inverse histogram, and resampling is performed by restarting the MD simulations from the new initial states to promote the conformational transition. In this process, the definition of the inverse histogram, which characterizes the rarely occurring states, is crucial for the efficiency of TBSA. In this study, we propose a simple modification of the inverse histogram to further accelerate the convergence of TBSA. As demonstrations of the modified TBSA, we applied it to (a) hydrogen bonding rearrangements of Met-enkephalin, (b) large-amplitude domain motions of Glutamine-Binding Protein, and (c) folding processes of the B domain of Staphylococcus aureus Protein A. All demonstrations numerically proved that the modified TBSA reproduced these biologically relevant rare events with nanosecond-order simulation times, although a set of microsecond-order, canonical MD simulations failed to reproduce the rare events, indicating the high efficiency of the modified TBSA. PMID:27070761

  6. Biological Production of a Hydrocarbon Fuel Intermediate Polyhydroxybutyrate (Phb) from a Process Relevant Lignocellulosic Derived Sugar

    SciTech Connect

    Wang, Wei; Mohagheghi, Ali; Mittal, Ashutosh; Pilath, Heidi; Johnson, David K.

    2015-03-22

    PHAs are synthesized by many microorganisms to serve as intracellular carbon storage molecules. In some bacterial strains, PHB can account for up to 80% of cell mass. In addition to its application in the packaging sector, PHB also has great potential as an intermediate in the production of hydrocarbon fuels. PHB can be thermally depolymerized and decarboxylated to propene which can be upgraded to hydrocarbon fuels via commercial oligomerization technologies. In recent years a great effort has been made in bacterial production of PHB, yet the production cost of the polymer is still much higher than conventional petrochemical plastics. The high cost of PHB is because the cost of the substrates can account for as much as half of the total product cost in large scale fermentation. Thus searching for cheaper and better substrates is very necessary for PHB production. In this study, we demonstrate production of PHB by Cupriavidus necator from a process relevant lignocellulosic derived sugar stream, i.e., saccharified hydrolysate slurry from pretreated corn stover. Good cell growth was observed on slurry saccharified with advanced enzymes and 40~60% of PHB was accumulated in the cells. The mechanism of inhibition in the toxic hydrolysate generated by pretreatment and saccharification of biomass, will be discussed.

  7. The autoxidation and proton dissociation constants of tertiary diphosphines: relevance to biological activity.

    PubMed

    Berners-Price, S J; Norman, R E; Sadler, P J

    1987-11-01

    The pKas and autoxidation properties of a number of diphosphines which exhibit varying degrees of antitumor and cytotoxic activity were investigated. Titration by HClO4 in CH3NO2 was used to determine pKas of the following diphosphines: R2P(CH2)nPR'2, where for R = R' = Ph, n = 1, 2, and 3 (dppm, dppe, and dppp respectively); for R = R' = Et, n = 2 (depe); for R = Ph, R' = Et, n = 2 (eppe); and for cis and trans Ph2PCH = CHPPh2 (dppey). The difference between the first and second protonation constants decreases as the length of the carbon chain between the two phosphorus centers increases. Unsaturation in the carbon chain lowers pKas. -PEt2 centers are apparently more basic than -PPh2 centers. Apart from electrostatic effects, the protonation of a given phosphine center appears to be independent of the substituents at the second phosphine center. The autoxidation reactions of dppm, dppe, dppp, depe, and cis-dppey were studied in a variety of solvents by 31P NMR spectroscopy. The ethyl-substituted diphosphines were much more rapidly oxidized than the phenyl-substituted, and the pathways of autoxidation differed. Generally, the phenyl-substituted diphosphines gave only mono- and dioxides, while the ethyl-substituted diphosphines additionally gave phosphinites and other oxidation products. The relevance of the autoxidation reactivity and the pKas to the contrasting antitumor activity of these diphosphines is discussed. PMID:2828542

  8. O2 reduction reaction by biologically relevant anionic ligand bound iron porphyrin complexes.

    PubMed

    Samanta, Subhra; Das, Pradip Kumar; Chatterjee, Sudipta; Sengupta, Kushal; Mondal, Biswajit; Dey, Abhishek

    2013-11-18

    Iron porphyrin complex with a covalently attached thiolate ligand and another with a covalently attached phenolate ligand has been synthesized. The thiolate bound complex shows spectroscopic features characteristic of P450, including the hallmark absorption spectrum of the CO adduct. Electrocatalytic O2 reduction by this complex, which bears a terminal alkyne group, is investigated by both physiabsorbing on graphite surfaces (fast electron transfer rates) and covalent attachment to azide terminated self-assembled monolayer (physiologically relevant electron transfer rates) using the terminal alkyne group. Analysis of the steady state electrochemical kinetics reveals that this catalyst can selectively reduce O2 to H2O with a second-order k(cat.) ~10(7) M(-1 )s(-1) at pH 7. The analogous phenolate bound iron porphyrin complex reduces O2 with a second-order rate constant of 10(5) M(-1) s(-1) under the same conditions. The anionic ligand bound iron porphyrin complexes catalyze oxygen reduction reactions faster than any known synthetic heme porphyrin analogues. The kinetic parameters of O2 reduction of the synthetic thiolate bound complex, which is devoid of any second sphere effects present in protein active sites, provide fundamental insight into the role of the protein environment in tuning the reactivity of thiolate bound iron porphyrin containing metalloenzymes. PMID:24171513

  9. Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies.

    PubMed

    Shaver, Timothy M; Lehmann, Brian D; Beeler, J Scott; Li, Chung-I; Li, Zhu; Jin, Hailing; Stricker, Thomas P; Shyr, Yu; Pietenpol, Jennifer A

    2016-08-15

    Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. Cancer Res; 76(16); 4850-60. ©2016 AACR. PMID:27231203

  10. Reactions of HNO with metal porphyrins: underscoring the biological relevance of HNO.

    PubMed

    Doctorovich, Fabio; Bikiel, Damian E; Pellegrino, Juan; Suárez, Sebastián A; Martí, Marcelo A

    2014-10-21

    Azanone ((1)HNO, nitroxyl) shows interesting yet poorly understood chemical and biological effects. HNO has some overlapping properties with nitric oxide (NO), sharing its biological reactivity toward heme proteins, thiols, and oxygen. Despite this similarity, HNO and NO show significantly different pharmacological effects. The high reactivity of HNO means that studies must rely on the use of donor molecules such as trioxodinitrate (Angeli's salt). It has been suggested that azanone could be an intermediate in several reactions and that it may be an enzymatically produced signaling molecule. The inherent difficulty in detecting its presence unequivocally prevents evidence from yielding definite answers. On the other hand, metalloporphyrins are widely used as chemical models of heme proteins, providing us with invaluable tools for the study of the coordination chemistry of small molecules, like NO, CO, and O2. Studies with transition metal porphyrins have shown diverse mechanistic, kinetic, structural, and reactive aspects related to the formation of nitrosyl complexes. Porphyrins are also widely used in technical applications, especially when coupled to a surface, where they can be used as electrochemical gas sensors. Given their versatility, they have not escaped their role as key players in chemical studies involving HNO. This Account presents the research performed during the last 10 years in our group concerning azanone reactions with iron, manganese, and cobalt porphyrins. We begin by describing their HNO trapping capabilities, which result in formation of the corresponding nitrosyl complexes. Kinetic and mechanistic studies of these reactions show two alternative operating mechanisms: reaction of the metal center with HNO or with the donor. Moreover, we have also shown that azanone can be stabilized by coordination to iron porphyrins using electron-attracting substituents attached to the porphyrin ring, which balance the negatively charged NO¯. Second, we

  11. Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids

    PubMed Central

    Teslovich, Tanya M.; Musunuru, Kiran; Smith, Albert V.; Edmondson, Andrew C.; Stylianou, Ioannis M.; Koseki, Masahiro; Pirruccello, James P.; Ripatti, Samuli; Chasman, Daniel I.; Willer, Cristen J.; Johansen, Christopher T.; Fouchier, Sigrid W.; Isaacs, Aaron; Peloso, Gina M.; Barbalic, Maja; Ricketts, Sally L.; Bis, Joshua C.; Aulchenko, Yurii S.; Thorleifsson, Gudmar; Feitosa, Mary F.; Chambers, John; Orho-Melander, Marju; Melander, Olle; Johnson, Toby; Li, Xiaohui; Guo, Xiuqing; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C.; Lange, Leslie A.; Smith, Joshua D.; Song, Kijoung; Zhao, Jing Hua; Yuan, Xin; Luan, Jian'an; Lamina, Claudia; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y.L.; Wright, Alan F.; Witteman, Jacqueline C.M.; Wilson, James F.; Willemsen, Gonneke; Wichmann, H-Erich; Whitfield, John B.; Waterworth, Dawn M.; Wareham, Nicholas J.; Waeber, Gérard; Vollenweider, Peter; Voight, Benjamin F.; Vitart, Veronique; Uitterlinden, Andre G.; Uda, Manuela; Tuomilehto, Jaakko; Thompson, John R.; Tanaka, Toshiko; Surakka, Ida; Stringham, Heather M.; Spector, Tim D.; Soranzo, Nicole; Smit, Johannes H.; Sinisalo, Juha; Silander, Kaisa; Sijbrands, Eric J.G.; Scuteri, Angelo; Scott, James; Schlessinger, David; Sanna, Serena; Salomaa, Veikko; Saharinen, Juha; Sabatti, Chiara; Ruokonen, Aimo; Rudan, Igor; Rose, Lynda M.; Roberts, Robert; Rieder, Mark; Psaty, Bruce M.; Pramstaller, Peter P.; Pichler, Irene; Perola, Markus; Penninx, Brenda W.J.H.; Pedersen, Nancy L.; Pattaro, Cristian; Parker, Alex N.; Pare, Guillaume; Oostra, Ben A.; O'Donnell, Christopher J.; Nieminen, Markku S.; Nickerson, Deborah A.; Montgomery, Grant W.; Meitinger, Thomas; McPherson, Ruth; McCarthy, Mark I.; McArdle, Wendy; Masson, David; Martin, Nicholas G.; Marroni, Fabio; Mangino, Massimo; Magnusson, Patrik K.E.; Lucas, Gavin; Luben, Robert; Loos, Ruth J. F.; Lokki, Maisa; Lettre, Guillaume; Langenberg, Claudia; Launer, Lenore J.; Lakatta, Edward G.; Laaksonen, Reijo; Kyvik, Kirsten O.; Kronenberg, Florian; König, Inke R.; Khaw, Kay-Tee; Kaprio, Jaakko; Kaplan, Lee M.; Johansson, Åsa; Jarvelin, Marjo-Riitta; Janssens, A. Cecile J.W.; Ingelsson, Erik; Igl, Wilmar; Hovingh, G. Kees; Hottenga, Jouke-Jan; Hofman, Albert; Hicks, Andrew A.; Hengstenberg, Christian; Heid, Iris M.; Hayward, Caroline; Havulinna, Aki S.; Hastie, Nicholas D.; Harris, Tamara B.; Haritunians, Talin; Hall, Alistair S.; Gyllensten, Ulf; Guiducci, Candace; Groop, Leif C.; Gonzalez, Elena; Gieger, Christian; Freimer, Nelson B.; Ferrucci, Luigi; Erdmann, Jeanette; Elliott, Paul; Ejebe, Kenechi G.; Döring, Angela; Dominiczak, Anna F.; Demissie, Serkalem; Deloukas, Panagiotis; de Geus, Eco J.C.; de Faire, Ulf; Crawford, Gabriel; Collins, Francis S.; Chen, Yii-der I.; Caulfield, Mark J.; Campbell, Harry; Burtt, Noel P.; Bonnycastle, Lori L.; Boomsma, Dorret I.; Boekholdt, S. Matthijs; Bergman, Richard N.; Barroso, Inês; Bandinelli, Stefania; Ballantyne, Christie M.; Assimes, Themistocles L.; Quertermous, Thomas; Altshuler, David; Seielstad, Mark; Wong, Tien Y.; Tai, E-Shyong; Feranil, Alan B.; Kuzawa, Christopher W.; Adair, Linda S.; Taylor, Herman A.; Borecki, Ingrid B.; Gabriel, Stacey B.; Wilson, James G.; Stefansson, Kari; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Krauss, Ronald M.; Mohlke, Karen L.; Ordovas, Jose M.; Munroe, Patricia B.; Kooner, Jaspal S.; Tall, Alan R.; Hegele, Robert A.; Kastelein, John J.P.; Schadt, Eric E.; Rotter, Jerome I.; Boerwinkle, Eric; Strachan, David P.; Mooser, Vincent; Holm, Hilma; Reilly, Muredach P.; Samani, Nilesh J; Schunkert, Heribert; Cupples, L. Adrienne; Sandhu, Manjinder S.; Ridker, Paul M; Rader, Daniel J.; van Duijn, Cornelia M.; Peltonen, Leena; Abecasis, Gonçalo R.; Boehnke, Michael; Kathiresan, Sekar

    2010-01-01

    Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. PMID:20686565

  12. Altitude training causes haematological fluctuations with relevance for the Athlete Biological Passport.

    PubMed

    Bonne, Thomas Christian; Lundby, Carsten; Lundby, Anne Kristine; Sander, Mikael; Bejder, Jacob; Nordsborg, Nikolai Baastrup

    2015-08-01

    The impact of altitude training on haematological parameters and the Athlete Biological Passport (ABP) was evaluated in international-level elite athletes. One group of swimmers lived high and trained high (LHTH, n = 10) for three to four weeks at 2130 m or higher whereas a control group (n = 10) completed a three-week training camp at sea-level. Haematological parameters were determined weekly three times before and four times after the training camps. ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (RET%), OFF score and the abnormal blood profile score (ABPS) were calculated using the Bayesian model. After altitude training, six swimmers exceeded the 99% ABP thresholds: two swimmers exceeded the OFF score thresholds at day +7; one swimmer exceeded the OFF score threshold at day +28; one swimmer exceeded the threshold for RET% at day +14; and one swimmer surpassed the ABPS threshold at day +14. In the control group, no values exceeded the individual ABP reference range. In conclusion, LHTH induces haematological changes in Olympic-level elite athletes which can exceed the individually generated references in the ABP. Training at altitude should be considered a confounding factor for ABP interpretation for up to four weeks after altitude exposure but does not consistently cause abnormal values in the ABP. PMID:25545030

  13. Next generation techniques in the high resolution spectroscopy of biologically relevant molecules.

    PubMed

    Neill, Justin L; Douglass, Kevin O; Pate, Brooks H; Pratt, David W

    2011-04-28

    Recent advances in the technology of test and measurement equipment driven by the computer and telecommunications industries have made possible the development of a new broadband, Fourier-transform microwave spectrometer that operates on principles similar to FTNMR. This technique uses a high sample-rate arbitrary waveform generator to construct a phase-locked chirped microwave pulse that gives a linear frequency sweep over a wide frequency range in 1 μs. The chirped pulse efficiently polarizes the molecular sample at all frequencies lying within this band. The subsequent free induction decay of this polarization is measured with a high-speed digitizer and then fast Fourier-transformed to yield a broadband, frequency-resolved rotational spectrum, spanning up to 11.5 GHz and containing lines that are as narrow as 100 kHz. This new technique is called chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. The technique offers the potential to determine the structural and dynamical properties of very large molecules solely from fully resolved pure rotational spectra. FTMW double resonance techniques employing a low-resolution UV laser facilitate an easy assignment of overlapping spectra produced by different conformers in the sample. Of particular interest are the energy landscapes of conformationally flexible molecules of biological importance, including studies of their interaction with solvent and/or other weakly bound molecules. An example is provided from the authors' work on p-methoxyphenethylamine, a neurotransmitter, and its complexes with water. PMID:21394332

  14. Photochemical reactions of metal nitrosyl complexes. Mechanisms of NO reactions with biologically relevant metal centers

    DOE PAGESBeta

    Ford, Peter C.

    2001-01-01

    Tmore » he discoveries that nitric oxide (a.k.a. nitrogen monoxide) serves important roles in mammalian bioregulation and immunology have stimulated intense interest in the chemistry and biochemistry of NO and derivatives such as metal nitrosyl complexes. Also of interest are strategies to deliver NO to biological targets on demand. One such strategy would be to employ a precursor which displays relatively low thermal reactivity but is photochemically active to release NO.his proposition led us to investigate laser flash and continuous photolysis kinetics of nitrosyl complexes such as the Roussin's iron-sulfur-nitrosyl cluster anions Fe 2 S 2 ( NO ) 4 2 − and Fe 4 S 3 ( NO ) 7 − and several ruthenium salen and porphyrin nitrosyls.hese include studies using metal-nitrosyl photochemistry as a vehicle for delivering NO to hypoxic cell cultures in order to sensitize γ -radiation damage. Also studied were the rates and mechanisms of NO “on” reactions with model water soluble heme compounds, the ferriheme protein met-myoglobin and various ruthenium complexes using ns laser flash photolysis techniques. An overview of these studies is presented.« less

  15. Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity

    PubMed Central

    Willenberg, Ina; Meschede, Anna K.; Gueler, Faikah; Jang, Mi-Sun; Shushakova, Nelli; Schebb, Nils Helge

    2015-01-01

    Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX–2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA–7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX–2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX–2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested. PMID:26440517

  16. Prognostic value and in vitro biological relevance of Neuropilin 1 and Neuropilin 2 in osteosarcoma.

    PubMed

    Boro, Aleksandar; Arlt, Matthias Je; Lengnick, Harald; Robl, Bernhard; Husmann, Maren; Bertz, Josefine; Born, Walter; Fuchs, Bruno

    2015-01-01

    Neoadjuvant chemotherapy in osteosarcoma increased the long-term survival of patients with localized disease considerably but metastasizing osteosarcoma remained largely treatment resistant. Neuropilins, transmembrane glycoproteins, are important receptors for VEGF dependent hyper-vascularization in tumor angiogenesis and their aberrant expression promotes tumorigenesis and metastasis in many solid tumors. Our analysis of Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) immunostaining in a tissue microarray of 66 osteosarcoma patients identified NRP2 as an indicator of poor overall, metastasis-free and progression free survival while NRP1 had no predictive value. Patients with tumors that expressed NRP2 in the absence of NRP1 had a significantly worse prognosis than NRP1(-)/NRP2(-), NRP1(+) or NRP1(+)/NRP2(+) tumors. Moreover, patients with overt metastases and with NRP2-positive primary tumors had a significantly shorter survival rate than patients with metastases but NRP2-negative tumors. Furthermore, the expression of both NRP1 and NRP2 in osteosarcoma cell lines correlated to a variable degree with the metastatic potential of the respective cell line. To address the functional relevance of Neuropilins for VEGF signaling we used shRNA mediated down-regulation and blocking antibodies of NRP1 and NRP2 in the metastatic 143B and HuO9-M132 cell lines. In 143B cells, VEGFA signaling monitored by AKT phosphorylation was more inhibited by blocking of NRP1, whereas in HuO9-M132 cells NRP2 blocking was more effective indicating that NRP1 and NRP2 can substitute each other in the functional interaction with VEGFR1. Altogether, these data point to NRP2 as a powerful prognostic marker in osteosarcoma and together with NRP1 as a novel target for tumor-suppressive therapy. PMID:26045903

  17. Biological processes and optical measurements near the sea surface: Some issues relevant to remote sensing

    NASA Technical Reports Server (NTRS)

    Cullen, John J.; Lewis, Marlon R.

    1995-01-01

    The advent of remote sensing, the develpmemt of new optical instrumentation, and the associated advances in hydrological optics have transformed oceanography; it is now feasible to describe ocean-scale biogeochemical dynamcis from satellite observations, verified and complemented by measurements from optical sensors on profilers, moorings, and drifters. Only near-surface observations are common to both remote sensing and in situ observation, so it is critical to understand processes in the upper euphotic zone. Unfortunately, the biological principles that must be used to interpret optical variability near the sea surface are weaker than we would like, because relatively few experiments and analyses have examined bio-optical relationships under high irradiance characteristic of the upper optical depth. Special consideration of this stratum is justified, because there is good evidence that bio-optical relationships are altered near the surface; (1) the fluorescence yield from chlorophyll declines, leading to bias in the estimation of pigment from fluorometry; (2) the modeled relationship between solar-stimulated fluorecence and photosynthesis seems to deviate significantly from that presented for the lower euphotic zone; and (3) carbon-specific and cellular attenuation cross sections of phytoplankton change substantially during exposures to bright light. Even the measurement of primary productivity is problematic near the sea surface, because vertical mixing is not simulated and artifactual inhibition of photosynthesis can result. These problems can be addressed by focusing more sampling effort, experimental simulation, and analytical consideration on the upper optical depth, and by shortening timescales for the measurement of marine photosynthesis. Special efforts to study near-surface processes are justified, because new bio-optical algorithms will require quantitaitve descriptions of the responses of phytoplankton to bright light.

  18. C-MAF oncogene dysregulation in multiple myeloma: frequency and biological relevance.

    PubMed

    Rasmussen, Thomas; Knudsen, Lene Meldgaard; Dahl, Inger Marie S; Johnsen, Hans Erik

    2003-10-01

    To investigate the frequency and possible biological consequences of c-maf dysregulation, we designed c-maf and IL-4 real-time RT-PCR assays for determination of c-maf and IL-4 mRNA levels. Using the c-maf real-time RT-PCR assay, we tested a panel of 14 B-cell lines, 135 diagnostic bone marrow (BM) samples from patients with multiple myeloma and 10 BM samples from normal donors. In B cell lines and flowsorted CD38++/CD19-/CD56++ myeloma plasma cells (N = 14) the c-maf/GAPDH and IL-4/GAPDH ratios were determined simultaneously using real time RT-PCR. All B cell lines used in the study were characterized by flow cytometry and tested for the presence of Ebstein-Barr virus (EBV). B-cell lines, that were PCR negative for EBV and had a phenotype typical for primary myeloma cells, expressed medium to high levels of c-maf mRNA. However, all EBV PCR positive cell lines, showed a more immature phenotype, lacked expression of aberrant surface markers and contained very low levels of c-maf mRNA. In 4.4% (6/135) of MM patients tested, a c-maf mRNA level comparable to the cell line RPMI 8226 containing at (16:22), translocation was found. In addition, all c-maf positive myeloma cell lines and CD38++/CD19-/CD56++ myeloma plasma cells tested were IL-4 negative. In conclusion, high levels of c-maf mRNA were observed in "true MM cell lines" and 4.4% of MM patients. Further, c-maf dysregulation in myeloma plasma cells did not cause induction of IL-4 transcription. PMID:14692531

  19. Developing mononuclear copper-active-oxygen complexes relevant to reactive intermediates of biological oxidation reactions.

    PubMed

    Itoh, Shinobu

    2015-07-21

    Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H(•) or e(-)/H(+) transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies. In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex

  20. Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

    PubMed Central

    Ogata, Toru; Shibamura, Hidenori; Tromp, Gerard; Sinha, Moumita; Goddard, Katrina A. B.; Sakalihasan, Natzi; Limet, Raymond; MacKean, Gerald L.; Arthur, Claudette; Sueda, Taijiro; Land, Susan; Kuivaniemi, Helena

    2005-01-01

    findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt−1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. Clinical Relevance Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual’s risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA. PMID:15944607

  1. The scaling law of climate change and its relevance to assessing (palaeo)biological responses

    NASA Astrophysics Data System (ADS)

    Kiessling, Wolfgang; Eichenseer, Kilian

    2014-05-01

    interglacials, are not monotonic, but punctuated by short-term cooling intervals. The fossil record tells us that biodiversity responded dramatically to ancient intervals of climate warming. We can now see that the apparently slower rates of change in some mass extinctions (Permian-Triassic, Triassic-Jurassic) were greater than today when the scaling law is considered. This reassures us that studying deep time patterns of organismic response to climate change is a worthwhile endeavor that is relevant for predicting the future. References Burrows, M. T., Schoeman, D. S., Buckley, L. B., Moore, P., Poloczanska, E. S., Brander, K. M., Brown, C., Bruno, J. F., Duarte, C. M., Halpern, B. S., Holding, J., Kappel, C. V., Kiessling, W., O'Connor, M. I., Pandolfi, J. M., Parmesan, C., Schwing, F. B., Sydeman, W. J., and Richardson, A. J.: The pace of shifting climate in marine and terrestrial ecosystems, Science, 334, 652-655, 2011. Gingerich, P. D.: Quantification and comparison of evolutionary rates, American Journal of Science, 293A, 453-478, 1993. Sadler, P. M.: Sediment accumulation rates and the completeness of stratigraphic sections, Journal of Geology, 89, 569-584, 1981. Sun, Y., Joachimski, M. M., Wignall, P. B., Yan, C., Chen, Y., Jiang, H., Wang, L., and Lai, X.: Lethally hot temperatures during the Early Triassic greenhouse, Science, 338, 366-370, 2012.

  2. Biologically relevant 3D tumor arrays: imaging-based methods for quantification of reproducible growth and analysis of treatment response

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Hasan, Tayyaba

    2011-02-01

    Three-dimensional in vitro tumor models have emerged as powerful research tools in cancer biology, though the vast potential of these systems as high-throughput, biologically relevant reporters of treatment response has yet to be adequately explored. Here, building on previous studies, we demonstrate the utility of using 3D models for ovarian and pancreatic cancers in conjunction with quantitative image processing to reveal aspects of growth behavior and treatment response that would not be evident without either modeling or quantitative analysis component. In this report we specifically focus on recent improvements in the imaging component of this integrative research platform and emphasize analysis to establish reproducible growth properties in 3D tumor arrays, a key consideration in establishing the utility of this platform as a reliable reporter of therapeutic response. Building on previous studies using automated segmentation of low magnification image fields containing large numbers of nodules to study size dependent treatment effects, we introduce an improvement to this method using multiresolution decomposition to remove gradient background from transmitted light images for more reliable feature identification. This approach facilitates the development of a new treatment response metric, disruption fraction (Dfrac), which quantifies dose dependent distribution shifts from nodular fragmentation induced by cytotoxic therapies. Using this approach we show that PDT treatment is associated with significant dose-dependent increases in Dfrac, while this is not observed with carboplatin treatment. The ability to quantify this response to therapy could play a key role in design of combination regimens involving these two modalities.

  3. Sex differences in panic-relevant responding to a 10% carbon dioxide-enriched air biological challenge.

    PubMed

    Nillni, Yael I; Berenz, Erin C; Rohan, Kelly J; Zvolensky, Michael J

    2012-01-01

    The current study examined sex differences in psychological (i.e., self-reported anxiety, panic symptoms, and avoidance) and physiological (i.e., heart rate and skin conductance level) response to, and recovery from, a laboratory biological challenge. Participants were a community-recruited sample of 128 adults (63.3% women; M(age)=23.2 years, SD=8.9) who underwent a 4-min 10% CO(2)-enriched air biological challenge. As predicted, women reported more severe physical panic symptoms and avoidance (i.e., less willingness to participate in another challenge) and demonstrated increased heart rate as compared to men above and beyond the variance accounted for by other theoretically relevant variables (recent panic attack history, neuroticism, and anxiety sensitivity). Additionally, women demonstrated a faster rate of recovery with respect to heart rate compared to men. These results are in line with literature documenting sex-specific differences in panic psychopathology, and results are discussed in the context of possible mechanisms underlying sex differences in panic vulnerability. PMID:22115836

  4. The practicalities and pitfalls of establishing a policy-relevant and cost-effective soil biological monitoring scheme.

    PubMed

    Faber, Jack H; Creamer, Rachel E; Mulder, Christian; Römbke, Jörg; Rutgers, Michiel; Sousa, J Paulo; Stone, Dorothy; Griffiths, Bryan S

    2013-04-01

    A large number of biological indicators have been proposed over the years for assessing soil quality. Although many of those have been applied in monitoring schemes across Europe, no consensus exists on the extent to which these indicators might perform best and how monitoring schemes can be further optimized in terms of scientific and policy relevance. Over the past decade, developments in environmental monitoring and risk assessment converged toward the use of indicators and endpoints that are related to soil functioning and ecosystem services. In view of the proposed European Union (EU) Soil Framework Directive, there is an urgent need to identify and evaluate indicators for soil biodiversity and ecosystem services. The recently started integrated project, Ecological Function and Biodiversity Indicators in European Soils (EcoFINDERS), aims to address this specific issue within the EU Framework Program FP7. Here, we 1) discuss how to use the concept of ecosystem services in soil monitoring, 2) review former and ongoing monitoring schemes, and 3) present an analysis of metadata on biological indicators in some EU member states. Finally, we discuss our experiences in establishing a logical sieve approach to devise a monitoring scheme for a standardized and harmonized application at European scale. PMID:23325463

  5. Spatial release from masking improves sound pattern discrimination along a biologically relevant pulse-rate continuum in gray treefrogs

    PubMed Central

    Ward, Jessica L.; Buerkle, Nathan P.; Bee, Mark A.

    2013-01-01

    Frogs form large choruses during the mating season in which males produce loud advertisement calls to attract females and repel rival males. High background noise levels in these social aggregations can impair vocal perception. In humans, spatial release from masking contributes to our ability to understand speech in noisy social groups. Here, we tested the hypothesis that spatial separation between target signals and ‘chorus-shaped noise’ improves the ability of female gray treefrogs (Hyla chrysoscelis) to perform a behavioral discrimination task based on perceiving differences in the pulsatile structure of advertisement calls. We used two-stimulus choice tests to measure phonotaxis (approach toward sound) in response to calls differing in pulse rate along a biologically relevant continuum between conspecific (50 pulses s−1) and heterospecific (20 pulses s−1) calls. Signals were presented in quiet, in colocated noise, and in spatially separated noise. In quiet conditions, females exhibited robust preferences for calls with relatively faster pulse rates more typical of conspecific calls. Behavioral discrimination between calls differing in pulse rate was impaired in the presence of colocated noise but similar between quiet and spatially separated noise conditions. Our results indicate that spatial release from energetic masking facilitates a biologically important temporal discrimination task in frogs. We discuss these results in light of previous work on spatial release from masking in frogs and other animals. PMID:24055623

  6. Culturally relevant inquiry-based laboratory module implementations in upper-division genetics and cell biology teaching laboratories.

    PubMed

    Siritunga, Dimuth; Montero-Rojas, María; Carrero, Katherine; Toro, Gladys; Vélez, Ana; Carrero-Martínez, Franklin A

    2011-01-01

    Today, more minority students are entering undergraduate programs than ever before, but they earn only 6% of all science or engineering PhDs awarded in the United States. Many studies suggest that hands-on research activities enhance students' interest in pursuing a research career. In this paper, we present a model for the implementation of laboratory research in the undergraduate teaching laboratory using a culturally relevant approach to engage students. Laboratory modules were implemented in upper-division genetics and cell biology courses using cassava as the central theme. Students were asked to bring cassava samples from their respective towns, which allowed them to compare their field-collected samples against known lineages from agricultural stations at the end of the implementation. Assessment of content and learning perceptions revealed that our novel approach allowed students to learn while engaged in characterizing Puerto Rican cassava. In two semesters, based on the percentage of students who answered correctly in the premodule assessment for content knowledge, there was an overall improvement of 66% and 55% at the end in the genetics course and 24% and 15% in the cell biology course. Our proposed pedagogical model enhances students' professional competitiveness by providing students with valuable research skills as they work on a problem to which they can relate. PMID:21885825

  7. The development of Army relevant peptide-based surface enhanced Raman scattering (SERS) sensors for biological threat detection

    NASA Astrophysics Data System (ADS)

    Farrell, Mikella E.; Strobbia, Pietro; Sarkes, Deborah A.; Stratis-Cullum, Dimitra N.; Cullum, Brian M.; Pellegrino, Paul M.

    2016-05-01

    The utility of peptide-based molecular sensing for the development of novel biosensors has resulted in a significant increase in their development and usage for sensing targets like chemical, biological, energetic and toxic materials. Using peptides as a molecular recognition element is particularly advantageous because there are several mature peptide synthesis protocols that already exist, peptide structures can be tailored, selected and manipulated to be highly discerning towards desired targets, peptides can be modified to be very stable in a host of environments and stable under many different conditions, and through the development of bifunctionalized peptides can be synthesized to also bind onto desired sensing platforms (various metal materials, glass, etc.). Two examples of the several Army relevant biological targets for peptide-based sensing platforms include Ricin and Abrin. Ricin and Abrin are alarming threats because both can be weaponized and there is no antidote for exposure. Combining the sensitivity of SERS with the selectivity of a bifunctional peptide allows for the emergence of dynamic hazard sensor for Army application.

  8. The relevance of physicochemical and biological parameters for setting emission limit values for plants treating complex industrial wastewaters.

    PubMed

    Huybrechts, Diane; Weltens, Reinhilde; Jacobs, Griet; Borburgh, Ab; Smets, Toon; Hoebeke, Lut; Polders, Caroline

    2014-02-01

    The influents of plants treating complex industrial wastewaters from third parties may contain a large variety of often unknown or unidentified potentially harmful substances. The conventional approach of assessing and regulating the effluents of these plants is to set emission limit values for a limited set of physicochemical parameters, such as heavy metals, biological oxygen demand, chemical oxygen demand and adsorbable organic halogen compounds. The objective of this study was to evaluate the relevance of physicochemical parameters for setting emission limit values for such plants based on a comparison of effluent analyses by physicochemical and biological assessment tools. The results show that physicochemical parameters alone are not sufficient to evaluate the effectiveness of the water treatment plants for removing hazardous compounds and to protect the environment. The introduction of toxicity limits and limits for the total bioaccumulation potential should be considered to supplement generic parameters such as chemical oxygen demand and adsorbable organic halogens. A recommendation is made to include toxicity screening as a technique to consider in the determination of best available techniques (BAT) during the upcoming revision of the BAT reference document for the waste treatment industries to provide a more rational basis in decisions on additional treatment steps. PMID:24142491

  9. Culturally Relevant Inquiry-Based Laboratory Module Implementations in Upper-Division Genetics and Cell Biology Teaching Laboratories

    PubMed Central

    Siritunga, Dimuth; Montero-Rojas, María; Carrero, Katherine; Toro, Gladys; Vélez, Ana; Carrero-Martínez, Franklin A.

    2011-01-01

    Today, more minority students are entering undergraduate programs than ever before, but they earn only 6% of all science or engineering PhDs awarded in the United States. Many studies suggest that hands-on research activities enhance students’ interest in pursuing a research career. In this paper, we present a model for the implementation of laboratory research in the undergraduate teaching laboratory using a culturally relevant approach to engage students. Laboratory modules were implemented in upper-division genetics and cell biology courses using cassava as the central theme. Students were asked to bring cassava samples from their respective towns, which allowed them to compare their field-collected samples against known lineages from agricultural stations at the end of the implementation. Assessment of content and learning perceptions revealed that our novel approach allowed students to learn while engaged in characterizing Puerto Rican cassava. In two semesters, based on the percentage of students who answered correctly in the premodule assessment for content knowledge, there was an overall improvement of 66% and 55% at the end in the genetics course and 24% and 15% in the cell biology course. Our proposed pedagogical model enhances students’ professional competitiveness by providing students with valuable research skills as they work on a problem to which they can relate. PMID:21885825

  10. Quantum Dots: An Insight and Perspective of Their Biological Interaction and How This Relates to Their Relevance for Clinical Use

    PubMed Central

    Clift, Martin J. D.; Stone, Vicki

    2012-01-01

    Due to their novel physico-chemical characteristics, semi-conductor nanocrystal quantum dots (QDs) provide an advantageous perspective towards numerous different consumer and medical applications. The most notable potential application of QDs is their use as therapeutic and diagnostic tools in nanomedicine. Despite the many benefits posed by QDs, the proposed, intentional exposure to humans has raised concerns towards their potential impact upon human health. These concerns are predominantly based upon the heterogeneous composition of QDs, which most commonly comprises of a cadmium-based core and zinc sulphide shell. Whilst other nanoparticle (NP) types possess a similar structure to QDs (i.e. core-shell technology (e.g. Fe2O3, Au and superparamagnetic iron oxide NPs)), the importance of the concerns surrounding human exposure to QDs is amplified further since, due to the sophisticated chemical and light-emitting properties of QDs, the use of these NPs within any (nano)medical setting/application could be suggested as realistic, rather than simply an advantageous possibility. It is therefore imperative that a thorough understanding of how QDs interact with various biological systems, predominantly those relative to humans and what the consequences of such interactions are is gained with extreme alacrity. It is the aim of this review to highlight the current knowledge base of QD-biological system interactions, where the knowledge gaps (still) remain and how the understanding of this interaction relates to the most notable of applications for QDs; their clinical relevance. PMID:22896769

  11. Metal-based antitumour drugs in the post-genomic era: what comes next?

    PubMed

    Sava, Gianni; Bergamo, Alberta; Dyson, Paul J

    2011-09-28

    In our Dalton Transactions Perspective article entitled, 'Metal-based antitumour drugs in the post genomic era', (Dalton Trans., 2006, 1929-1933) we discussed metal-based drugs in light of past decades of research. We concluded that the post-genomic era would dictate a change in the direction of the field with knowledge of the genome increasingly allowing protein targets to be identified and not simply assuming that DNA is the only relevant target of metal-based drugs. Since our article was published new insights into the mode of action of metal-based drugs have emerged making some older findings increasingly relevant to current drug design. In this article we discuss these developments in terms of what we believe should be the future direction for the field. PMID:21725573

  12. Functionally relevant microorganisms to enhanced biological phosphorus removal performance at full-scale wastewater treatment plants in the United States.

    PubMed

    Gu, April Z; Saunders, A; Neethling, J B; Stensel, H D; Blackall, L L

    2008-08-01

    The abundance and relevance ofAccumulibacter phosphatis (presumed to be polyphosphate-accumulating organisms [PAOs]), Competibacter phosphatis (presumed to be glycogen-accumulating organisms [GAOs]), and tetrad-forming organisms (TFOs) to phosphorus removal performance at six full-scale enhanced biological phosphorus removal (EBPR) wastewater treatment plants were investigated. Coexistence of various levels of candidate PAOs and GAOs were found at these facilities. Accumulibacter were found to be 5 to 20% of the total bacterial population, and Competibacter were 0 to 20% of the total bacteria population. The TFO abundance varied from nondetectable to dominant. Anaerobic phosphorus (P) release to acetate uptake ratios (P(rel)/HAc(up)) obtained from bench tests were correlated positively with the abundance ratio of Accumulibacter/(Competibacter +TFOs) and negatively with the abundance of (Competibacter +TFOs) for all plants except one, suggesting the relevance of these candidate organisms to EBPR processes. However, effluent phosphorus concentration, amount of phosphorus removed, and process stability in an EBPR system were not directly related to high PAO abundance or mutually exclusive with a high GAO fraction. The plant that had the lowest average effluent phosphorus and highest stability rating had the lowest P(rel)/HAc(up) and the most TFOs. Evaluation of full-scale EBPR performance data indicated that low effluent phosphorus concentration and high process stability are positively correlated with the influent readily biodegradable chemical oxygen demand-to-phosphorus ratio. A system-level carbon-distribution-based conceptual model is proposed for capturing the dynamic competition between PAOs and GAOs and their effect on an EBPR process, and the results from this study seem to support the model hypothesis. PMID:18751532

  13. Functionalization of manganite nanoparticles and their interaction with biologically relevant small ligands: Picosecond time-resolved FRET studies

    NASA Astrophysics Data System (ADS)

    Giri, Anupam; Makhal, Abhinandan; Ghosh, Barnali; Raychaudhuri, A. K.; Pal, Samir Kumar

    2010-12-01

    We report molecular functionalization of the promising manganite nanoparticles La0.67Sr0.33MnO3 (LSMO) for their solubilization in aqueous environments. The functionalization of individual NPs with the biocompatible citrate ligand, as confirmed by Fourier transform infrared (FTIR) spectroscopy, reveals that citrates are covalently attached to the surface of the NPs. UV-VIS spectroscopic studies on the citrate functionalized NPs reveals an optical band in the visible region. Uniform size selectivity (2.6 nm) of the functionalization process is confirmed from high resolution transmission electron microscope (HRTEM). In the present study we have used the optical band of the functionalized NPs to monitor their interaction with other biologically important ligands. Förster resonance energy transfer (FRET) of a covalently attached probe4-nitrophenylanthranilate (NPA) with the capped NPs confirm the attachment of the NPA ligands to the surface functional group (-OH) of the citrate ligand. The FRET of a DNA base mimic, 2-aminopurine (2AP), with the NPs confirms the surface adsorption of 2AP. Our study may find relevance in the study of the interaction of individual manganite NPs with drug/ligand molecules.We report molecular functionalization of the promising manganite nanoparticles La0.67Sr0.33MnO3 (LSMO) for their solubilization in aqueous environments. The functionalization of individual NPs with the biocompatible citrate ligand, as confirmed by Fourier transform infrared (FTIR) spectroscopy, reveals that citrates are covalently attached to the surface of the NPs. UV-VIS spectroscopic studies on the citrate functionalized NPs reveals an optical band in the visible region. Uniform size selectivity (2.6 nm) of the functionalization process is confirmed from high resolution transmission electron microscope (HRTEM). In the present study we have used the optical band of the functionalized NPs to monitor their interaction with other biologically important ligands. F

  14. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles.

    PubMed

    Monopoli, Marco P; Walczyk, Dorota; Campbell, Abigail; Elia, Giuliano; Lynch, Iseult; Bombelli, Francesca Baldelli; Dawson, Kenneth A

    2011-03-01

    It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future. PMID:21288025

  15. Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin

    NASA Astrophysics Data System (ADS)

    Kleinnijenhuis, Anne J.; Mihalca, Romulus; Heeren, Ron M. A.; Heck, Albert J. R.

    2006-07-01

    Doubly protonated ions of the disulfide bond containing nonapeptide hormone oxytocin and oxytocin complexes with different transition metal ions, that have biological relevance under physiological conditions, were subjected to electron capture dissociation (ECD) to probe their structural features in the gas phase. Although, all the ECD spectra were strikingly different, typical ECD behavior was observed for complexes of the nonapeptide hormone oxytocin with Ni2+, Co2+ and Zn2+, i.e., abundant c/z' and a'/y backbone cleavages and ECD characteristic S-S and S-C bond cleavages were observed. We propose that, although in the oxytocin-transition metal ion complexes the metal ions serve as the main initial capture site, the captured electron is transferred to other sites in the complex to form a hydrogen radical, which drives the subsequent typical ECD fragmentations. The complex of oxytocin with Cu2+ displayed noticeably different ECD behavior. The fragment ions were similar to fragment ions typically observed with low-energy collision induced dissociation (CID). We propose that the electrons captured by the oxytocin-Cu2+ complex might be favorably involved in reducing the Cu2+ metal ion to Cu+. Subsequent energy redistribution would explain the observed low-energy CID-type fragmentations. Electron capture resulted also in quite different specific cleavage sites for the complexes of oxytocin with Ni2+, Co2+ and Zn2+. This is an indication for structural differences in these complexes possibly linked to their significantly different biological effects on oxytocin-receptor binding, and suggests that ECD may be used to study subtle structural differences in transition metal ion-peptide complexes.

  16. Metal-Based Nanoparticles and the Immune System: Activation, Inflammation, and Potential Applications

    PubMed Central

    Luo, Yueh-Hsia; Chang, Louis W.; Lin, Pinpin

    2015-01-01

    Nanomaterials, including metal-based nanoparticles, are used for various biological and medical applications. However, metals affect immune functions in many animal species including humans. Different physical and chemical properties induce different cellular responses, such as cellular uptake and intracellular biodistribution, leading to the different immune responses. The goals of this review are to summarize and discuss the innate and adaptive immune responses triggered by metal-based nanoparticles in a variety of immune system models. PMID:26125021

  17. A short-term colorectal cancer sphere culture as a relevant tool for human cancer biology investigation

    PubMed Central

    Weiswald, L-B; Richon, S; Massonnet, G; Guinebretière, J-M; Vacher, S; Laurendeau, I; Cottu, P; Marangoni, E; Nemati, F; Validire, P; Bellet, D; Bièche, I; Dangles-Marie, V

    2013-01-01

    Background: Ex vivo colospheres have been previously characterised as a colorectal cancer (CRC) well-rounded multicellular model, exclusively formed by carcinoma cells, and derived from fresh CRC tissue after mechanical dissociation. The ability to form colospheres was correlated with tumour aggressiveness. Their three-dimensional conformation prompted us to further investigate their potential interest as a preclinical cancer tool. Methods: Patient-derived CRC xenografts were used to produce numerous colospheres. Mechanism of formation was elucidated by confocal microscopy. Expression analysis of a panel of 64 selected cancer-related genes by real-time qRT–PCR and hierarchical clustering allowed comparison of colospheres with parent xenografts. In vitro and in vivo assays were performed for migration and chemosensitivity studies. Results: Colospheres, formed by tissue remodelling and compaction, remained viable several weeks in floating conditions, escaping anoikis through their strong cell–cell interactions. Colospheres matched the gene expression profile of the parent xenograft tissue. Colosphere-forming cells migrated in collagen I matrix and metastasised when subrenally implanted in nude mice. Besides, the colosphere responses to 5-fluorouracil and irinotecan, two standard drugs in CRC, reproduced those of the in vivo original xenografts. Conclusion: Colospheres closely mimic biological characteristics of in vivo CRC tumours. Consequently, they would be relevant ex vivo CRC models. PMID:23538387

  18. Generation of hydroxyl radical by chromate in biologically relevant systems: role of Cr(V) complexes versus tetraperoxochromate(V).

    PubMed

    Shi, X; Dalal, N S

    1994-09-01

    While Cr(V) species and .OH radicals have been suggested to play significant roles in the mechanism of chromate-related carcinogenesis, controversy still exists regarding the identity of the Cr(V) species and their role in the generation of .OH radicals. Some recent studies have suggested that the primary Cr(V) species involved is the tetraperoxochromate(V) (CrO8(3-)) ion, which produces .OH radical either on decomposition or by reaction with H2O2. The present study utilized ESR and spin trapping techniques to probe this mechanism. The results obtained show that (i) CrO8(3-) is not formed in any significant quantity in the reaction of chromate with biologically relevant reductants such as glutathione, glutathione reductase, NAD(P)H, ascorbate, vitamin B2, etc. (ii) Decomposition of CrO8(3-), or its reaction with H2O2 does not generate any significant amount of .OH radicals. (iii) The major Cr(V) species formed are complexes of Cr(V) with reductant moieties as ligands. (iv) These Cr(V) complexes generate .OH radicals from H2O2 via Fenton-like reaction. The present study thus disagrees with the recently proposed "tetraperoxochromate(V) theory of carcinogenesis from chromate." Instead, it suggests an alternative mechanism, which might be labeled as "the Cr(V)-complexation-Fenton reaction model of carcinogenesis from chromate. PMID:7843104

  19. Alkali Metal Ion Complexes with Phosphates, Nucleotides, Amino Acids, and Related Ligands of Biological Relevance. Their Properties in Solution.

    PubMed

    Crea, Francesco; De Stefano, Concetta; Foti, Claudia; Lando, Gabriele; Milea, Demetrio; Sammartano, Silvio

    2016-01-01

    Alkali metal ions play very important roles in all biological systems, some of them are essential for life. Their concentration depends on several physiological factors and is very variable. For example, sodium concentrations in human fluids vary from quite low (e.g., 8.2 mmol dm(-3) in mature maternal milk) to high values (0.14 mol dm(-3) in blood plasma). While many data on the concentration of Na(+) and K(+) in various fluids are available, the information on other alkali metal cations is scarce. Since many vital functions depend on the network of interactions occurring in various biofluids, this chapter reviews their complex formation with phosphates, nucleotides, amino acids, and related ligands of biological relevance. Literature data on this topic are quite rare if compared to other cations. Generally, the stability of alkali metal ion complexes of organic and inorganic ligands is rather low (usually log K < 2) and depends on the charge of the ligand, owing to the ionic nature of the interactions. At the same time, the size of the cation is an important factor that influences the stability: very often, but not always (e.g., for sulfate), it follows the trend Li(+) > Na(+) > K(+) > Rb(+) > Cs(+). For example, for citrate it is: log K ML = 0.88, 0.80, 0.48, 0.38, and 0.13 at 25 °C and infinite dilution. Some considerations are made on the main aspects related to the difficulties in the determination of weak complexes. The importance of the alkali metal ion complexes was also studied in the light of modelling natural fluids and in the use of these cations as probes for different processes. Some empirical relationships are proposed for the dependence of the stability constants of Na(+) complexes on the ligand charge, as well as for correlations among log K values of NaL, KL or LiL species (L = generic ligand). PMID:26860301

  20. The effect of anaesthetics on the properties of a lipid membrane in the biologically relevant phase: a computer simulation study.

    PubMed

    Fábián, Balázs; Darvas, Mária; Picaud, Sylvain; Sega, Marcello; Jedlovszky, Pál

    2015-06-14

    Molecular dynamics simulations of the fully hydrated neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing four different general anaesthetic molecules, namely chloroform, halothane, diethyl ether and enflurane, have been simulated at two different pressures, i.e., at 1 bar and 1000 bar, at the temperature of 310 K. At this temperature the model used in this study is known to be in the biologically most relevant liquid crystalline (Lα) phase. To find out which properties of the membrane might possibly be related to the molecular mechanism of anaesthesia, we have been looking for properties that change in the same way in the presence of any general anaesthetic molecule, and change in the opposite way by the increase of pressure. This way, we have ruled out the density distribution of various groups along the membrane normal axis, orientation of the lipid heads and tails, self-association of the anaesthetics, as well as the local order of the lipid tails as possible molecular reasons of anaesthesia. On the other hand, we have found that the molecular surface area, and hence also the molecular volume of the membrane, is increased by the presence of any anaesthetic molecule, and decreased by the pressure, in accordance with the more than half a century old critical volume hypothesis. We have also found that anaesthetic molecules prefer two different positions along the membrane normal axis, namely the middle of the membrane and the outer edge of the hydrocarbon region, close to the polar headgroups. The increase of pressure is found to decrease the former, and increase the latter preference, and hence it might also be related to the pressure reversal of anaesthesia. PMID:25975364

  1. UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement.

    PubMed Central

    Nakazawa, H; English, D; Randell, P L; Nakazawa, K; Martel, N; Armstrong, B K; Yamasaki, H

    1994-01-01

    Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-specific p53 gene mutations in UV-exposed normal skin. The methods are based on mutant allele-specific PCRs and ligase chain reactions and designed to detect CC to TT mutations at codons 245 and 247/248, using 10 micrograms of DNA samples. These specific mutations in the p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene were detected in cultured human skin cells only after UV irradiation, and the mutation frequency increased with increasing UV dose. Seventeen of 23 samples of normal skin from sun-exposed sites (74%) on Australian skin cancer patients contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on volunteers living in France carried such mutations. Our results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation. Measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer. Images Fig. 2 Fig. 3 Fig. 4 PMID:8278394

  2. V-type nerve agents phosphonylate ubiquitin at biologically relevant lysine residues and induce intramolecular cyclization by an isopeptide bond.

    PubMed

    Schmidt, Christian; Breyer, Felicitas; Blum, Marc-Michael; Thiermann, Horst; Worek, Franz; John, Harald

    2014-08-01

    Toxic organophosphorus compounds (e.g., pesticides and nerve agents) are known to react with nucleophilic side chains of different amino acids (phosphylation), thus forming adducts with endogenous proteins. Most often binding to serine, tyrosine, or threonine residues is described as being of relevance for toxicological effects (e.g., acetylcholinesterase and neuropathy target esterase) or as biomarkers for post-exposure analysis (verification, e.g., albumin and butyrylcholinesterase). Accordingly, identification of novel protein targets might be beneficial for a better understanding of the toxicology of these compounds, revealing new bioanalytical verification tools, and improving knowledge on chemical reactivity. In the present study, we investigated the reaction of ubiquitin (Ub) with the V-type nerve agents Chinese VX, Russian VX, and VX in vitro. Ub is a ubiquitous protein with a mass of 8564.8 Da present in the extra- and intracellular space that plays an important physiological role in several essential processes (e.g., proteasomal degradation, DNA repair, protein turnover, and endocytosis). Reaction products were analyzed by matrix-assisted laser desorption/ionization-time-of-flight- mass spectrometry (MALDI-TOF MS) and μ-high-performance liquid chromatography online coupled to UV-detection and electrospray ionization MS (μHPLC-UV/ESI MS). Our results originally document that a complex mixture of at least mono-, di, and triphosphonylated Ub adducts was produced. Surprisingly, peptide mass fingerprint analysis in combination with MALDI and ESI MS/MS revealed that phosphonylation occurred with high selectivity in at least 6 of 7 surface-exposed lysine residues that are essential for the biological function of Ub. These reaction products were found not to age. In addition, we herein report for the first time that phosphonylation induced intramolecular cyclization by formation of an isopeptide bond between the ε-amino group of a formerly phosphonylated

  3. Design, Development, and Psychometric Analysis of a General, Organic, and Biological Chemistry Topic Inventory Based on the Identified Main Chemistry Topics Relevant to Nursing Clinical Practice

    ERIC Educational Resources Information Center

    Brown, Corina E.

    2013-01-01

    This two-stage study focused on the undergraduate nursing course that covers topics in general, organic, and biological (GOB) chemistry. In the first stage, the central objective was to identify the main concepts of GOB chemistry relevant to the clinical practice of nursing. The collection of data was based on open-ended interviews of both nursing…

  4. Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats

    EPA Science Inventory

    Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the curren...

  5. Establishing the "Biological Relevance" of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels.

    PubMed

    Gray, Leon Earl; Furr, Johnathan; Tatum-Gibbs, Katoria R; Lambright, Christy; Sampson, Hunter; Hannas, Bethany R; Wilson, Vickie S; Hotchkiss, Andrew; Foster, Paul M D

    2016-01-01

    Phthalate esters (PEs) constitute a large class of compounds that are used for many consumer product applications. Many of the C2-C7 di-ortho PEs reduce fetal testicular hormone and gene expression levels in rats resulting in adverse effects seen later in life but it appears that relatively large reductions in fetal testosterone (T) levels and testis gene expression may be required to adversely affect reproductive development (Hannas, B. R., Lambright, C. S., Furr, J., Evans, N., Foster, P. M., Gray, E. L., and Wilson, V. S. (2012). Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: a targeted RT-PCR array approach for defining relative potency. Toxicol. Sci. 125, 544-557). The objectives of this study were (1) to model the relationships between changes in fetal male rat plasma testosterone (PT), T levels in the testis (TT), T production (PROD), and testis gene expression with the reproductive malformation rates, and (2) to quantify the "biologically relevant reductions" (BRRs) in fetal T necessary to induce adverse effects in the offspring. In the fetal experiment, Harlan Sprague-Dawley rats were dosed with dipentyl phthalate (DPeP) at 0, 11, 33, 100, and 300 mg/kg/day from gestational days (GD) 14-18 and fetal testicular T, PT levels, and T Prod and gene expression were assessed on GD 18. In the postnatal experiment, rats were dosed with DPeP from GD 8-18 and reproductive development was monitored through adulthood. The dose-response curves for TT levels (ED(50) = 53 mg/kg) and T PROD (ED(50) = 45 mg/kg) were similar, whereas PT was reduced at ED50 = 19 mg/kg. When the reductions in TPROD and Insl3 mRNA were compared with the postnatal effects of in utero DPeP, dose-related reproductive alterations were noted when T PROD and Insl3 mRNA were reduced by >45% and 42%, respectively. The determination of BRR levels may enable risk assessors to utilize fetal endocrine data to help establish points of departure for

  6. "Evo in the News": A Pedagogical Tool to Enhance Students' Perceptions of the Relevance of Evolutionary Biology

    ERIC Educational Resources Information Center

    Infanti, Lynn M.

    2012-01-01

    This investigation evaluated the effects of the use of the pedagogical tool "Evo in the News" on the attitudes toward and knowledge of biological evolution in a sample of undergraduate non-major biology students at a large, private research university. In addition, this study looked at the initial attitudes of the students and their…

  7. Hydration Structures and Thermodynamic Properties of Cationized Biologically Relevant Molecules, M+(Indole)(H2O)n (M = Na, K; n = 3-6)

    NASA Astrophysics Data System (ADS)

    Ke, Haochen; Lisy, James

    2015-03-01

    The balance between various noncovalent interactions plays a key role in determining the hydration structures and thermodynamic properties of biologically relevant molecules in biological mediums. Such properties of biologically relevant molecules are closely related to their often unique biological functionalities. The indole moiety is a basic functional group of many important neurotransmitters and hormones and has been used as tractable model for more complex biomolecules. The cationized indole water cluster is a perfect system for the quantitative and systematic study of the competition and cooperation of noncovalent interactions, as electrostatic interactions can be adjusted by introducing different monovalent cations and hydrogen bonding interactions can be adjusted by varying the level of hydration. IRPD spectra with isotopic (H/D) analysis helped unravel the overlapping N-H and O-H stretching modes, a major challenge of earlier studies. Thermodynamic analysis using relative Gibbs free energies, for energy ordering, together with spectral analysis provided unambiguous assignment of spectral features and structural configurations. A systematic hydration model with an in-depth account of noncovalent interactions is presented.

  8. Modeling pCO{sub 2} in the upper ocean: A review of relevant physical, chemical, and biological processes

    SciTech Connect

    1990-12-01

    The pCO{sub 2} of the surface ocean is controlled by a combination of physical, chemical, and biological processes. Modeling surface ocean pCO{sub 2} is analogous to modeling sea surface temperature (SST), in that sea surface pCO{sub 2} is affected by fluxes across the air-sea interface and by exchange with deeper water. However, pCO{sub 2} is also affected by chemical and biological processes which have no analog in SST. Seawater pCO{sub 2} is buffered by pH equilibrium reactions between the species CO{sub 2}, HCO{sub 3}-, and CO{sub 3}{sup =}. This effect provides an effective reservoir for CO{sub 2} in seawater that is 10 times larger than it would be for an unbuffered gas. The equilibrium between dissolved and atmospheric CO{sub 2} is sensitive to temperature, tending to higher pCO{sub 2} in warmer water. Biological export of carbon as sinking particles maintains a gradient of pCO{sub 2}, with lower values near the surface (this processes is called the {open_quotes}biological pump{close_quotes}). In most of the ocean, biological activity removes all of the available nutrients from the surface water; that is, the rate of carbon export in these locations is limited by the rate of nutrient supply to the euphotic zone. However, in much of the high-latitude oceans, primary production does not deplete the euphotic zone of nutrients, a fact to which the atmospheric pCO{sub 2} is extraordinarily sensitive. Understanding the limits to phytoplankton growth in the high latitudes, and how these limits might change under different climatic regimes, is essential to prediction of future ocean uptake of fossil fuel CO{sub 2}.

  9. Classical conditioning of sexual arousal in women and men: effects of varying awareness and biological relevance of the conditioned stimulus.

    PubMed

    Hoffmann, Heather; Janssen, Erick; Turner, Stefanie L

    2004-02-01

    Classical conditioning of sexual arousal has previously been demonstrated in human males but not in females. This study explored the role of classical (Pavlovian) conditioning in the activation of genital sexual arousal in both women and men, and assessed the effects of varying conditioned stimulus (CS) duration (subliminal/conscious) and relevance (sexually relevant/irrelevant). Twenty-seven female and 29 male participants received either subliminal or conscious presentations of a photograph of either a sexually relevant (abdomen of the opposite sex) or irrelevant (gun) CS+, which was followed by the unconditioned stimulus (US-erotic film clip). A CS-, a stimulus not paired with the US, was also included in the 11 conditioning trials. Ten participants were assigned to a control group that received unpaired presentations of the CS+, CS-, and the US. Both women and men showed more evidence of conditioning to the abdomen than to the gun when the CS was presented subliminally. When consciously perceived CSs were used, however, gender differences emerged. Men again showed the expected cue-to-consequence specificity but women showed the opposite effect, that is, conditioned arousal to the sexually irrelevant rather than to the relevant CS. The latter finding may be due to increased autonomic nervous system arousal associated with the irrelevant CS (gun). Skin conductance responses indicated more general arousal to the gun than to the male abdomen in women. This is the first study to compare the effects of a subliminal and conscious CS and to find classical conditioning of sexual arousal in women. PMID:14739689

  10. Evaluating emotional sensitivity and tolerance factors in the prediction of panic-relevant responding to a biological challenge.

    PubMed

    Kutz, Amanda; Marshall, Erin; Bernstein, Amit; Zvolensky, Michael J

    2010-01-01

    The current study investigated anxiety sensitivity, distress tolerance (Simons & Gaher, 2005), and discomfort intolerance (Schmidt, Richey, Cromer, & Buckner, 2007) in relation to panic-relevant responding (i.e., panic attack symptoms and panic-relevant cognitions) to a 10% carbon dioxide enriched air challenge. Participants were 216 adults (52.6% female; M(age)=22.4, SD=9.0). A series of hierarchical multiple regressions was conducted with covariates of negative affectivity and past year panic attack history in step one of the model, and anxiety sensitivity, discomfort intolerance, and distress tolerance entered simultaneously into step two. Results indicated that anxiety sensitivity, but not distress tolerance or discomfort intolerance, was significantly incrementally predictive of physical panic attack symptoms and cognitive panic attack symptoms. Additionally, anxiety sensitivity was significantly predictive of variance in panic attack status during the challenge. These findings emphasize the important, unique role of anxiety sensitivity in predicting risk for panic psychopathology, even when considered in the context of other theoretically relevant emotion vulnerability variables. PMID:19720496

  11. Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives.

    PubMed

    Šegan, Sandra; Trifković, Jelena; Verbić, Tatjana; Opsenica, Dejan; Zlatović, Mario; Burnett, James; Šolaja, Bogdan; Milojković-Opsenica, Dušanka

    2013-01-01

    The physicochemical properties, retention parameters (R(M)(0)), partition coefficients (logP(OW)), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R(M)(0), logP(OW), and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles. PMID:22985530

  12. Effect of Co-Existing Biologically Relevant Molecules and Ions on DNA Photocleavage Caused by Pyrene and its Derivatives

    PubMed Central

    Wang, Shuguang; Yu, Hongtao

    2005-01-01

    Inorganic ions, coenzymes, amino acids, and saccharides could co-exist with toxic environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), in the cell. The presence of these co-existing chemicals can modulate the toxicity of the PAHs. One of the genotoxic effects by PAHs is light-induced cleavage, or photocleavage, of DNA. The effect of inorganic ions I−, Na+, Ca2+, Mg2+, Fe3+, Mn2+, Cu2+, and Zn2+ and biological molecules riboflavin, histidine, mannitol, nicotinamide adenine dinucleotide (NAD), glutathione, and glutamic acid on the DNA photocleavage by pyrene, 1-hydroxypyrene (1-HP), and 1-aminopyrene (1-AP), is studied. The non-transition metal ions Na+, Ca2+, and Mg2+, usually have very little inhibitory effects, while the transition metal ions Fe3+, Cu2+, and Zn2+ enhance, Mn2+ inhibits the DNA photocleavage. The effect by biological molecules is complex, depending on the photochemical reaction mechanisms of the compounds tested (1-AP, 1-HP and pyrene) and on the chemical nature of the added biological molecules. Riboflavin, histidine, and mannitol enhance DNA photocleavage by all three compounds, except that mannitol has no effect on the photocleavage of DNA by pyrene. Glutathione inhibits the DNA photocleavage by 1-AP and 1-HP, but has no effect on that by pyrene. NAD enhances the DNA photocleavage by 1-AP, but has no effect on that by 1-HP and pyrene. Glutamic acid enhances the DNA photocleavage by 1-AP and pyrene, but inhibits that by 1-HP. These results show that the co-existing chemicals may have a profound effect on the toxicity of PAHs, or possibly on the toxicity of many other chemicals. Therefore, if one studies the toxic effects of PAHs or other toxic chemicals, the effect of the co-existing chemicals or ions needs to be considered. PMID:16705811

  13. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance.

    PubMed

    Chowbina, Sudhir; Hammamieh, Rasha; Kumar, Raina; Chakraborty, Nabarun; Yang, Ruoting; Mudunuri, Uma; Jett, Marti; Palma, Joseph M; Stephens, Robert

    2013-01-01

    SysBioCube is an integrated data warehouse and analysis platform for experimental data relating to diseases of military relevance developed for the US Army Medical Research and Materiel Command Systems Biology Enterprise (SBE). It brings together, under a single database environment, pathophysio-, psychological, molecular and biochemical data from mouse models of post-traumatic stress disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will organize, centralize and normalize this data and provide an access portal for subsequent analysis to the SBE. It provides new or expanded browsing, querying and visualization to provide better understanding of the systems biology of PTSD, all brought about through the integrated environment. We employ Oracle database technology to store the data using an integrated hierarchical database schema design. The web interface provides researchers with systematic information and option to interrogate the profiles of pan-omics component across different data types, experimental designs and other covariates. PMID:24303294

  14. Neocryptolepine: A Promising Indoloisoquinoline Alkaloid with Interesting Biological Activity. Evaluation of the Drug and its Most Relevant Analogs.

    PubMed

    Larghi, Enrique L; Bracca, Andrea B J; Arroyo Aguilar, Abel A; Heredia, Daniel A; Pergomet, Jorgelina L; Simonetti, Sebastian O; Kaufman, Teodoro S

    2015-01-01

    Plants are one of the most important resources for the discovery of new drugs. The potential of natural compounds as new drug leads is clearly illustrated by the discovery and development of many modern medicines. This is an encouraging factor that drives natural products research in the vegetable kingdom. Neocryptolepine is a tetracyclic nitrogen heterocycle isolated from the African climber Cryptolepis sanguinolenta, which is widely used in traditional African medicine in many countries of Central and West Africa. The natural product is one of the representative examples of the small family of indolo[2,3-b]quinoline alkaloids, being endowed of multiple biological activities, including DNA-binding and inhibition of the enzyme topoisomerase II. It is also cytotoxic, antibacterial, antifungal and molluscicidal, also displaying antiprotozoal activity, particularly as antitrypanosomal, antileishmanial, antischistosomal and antiplasmodial. Some of these activities have been related to the product's ability to bind to DNA and to inhibit topoisomerase II; however, the exact mechanisms behind all of the observed bioactivities have not been comprehensively clarified. Major research activities regarding neocryptolepine have been focused into two seemingly opposite fields, related to its cytotoxic and antimalarial properties. Optimization of the natural product as a cytotoxic agent implied improvements in its bioavailability and activity, while the need of non-cytotoxic compounds guided the design and optimization of antimalarial agents. Therefore, the aim of the present article is to systematically review the current knowledge about the diversity of the biological activities related to neocryptolepine, its analogs and derivatives. PMID:25915612

  15. A Heteroepitaxial Perovskite Metal-Base Transistor

    SciTech Connect

    Yajima, T.; Hikita, Y.; Hwang, H.Y.; /Tokyo U. /JST, PRESTO /SLAC

    2011-08-11

    'More than Moore' captures a concept for overcoming limitations in silicon electronics by incorporating new functionalities in the constituent materials. Perovskite oxides are candidates because of their vast array of physical properties in a common structure. They also enable new electronic devices based on strongly-correlated electrons. The field effect transistor and its derivatives have been the principal oxide devices investigated thus far, but another option is available in a different geometry: if the current is perpendicular to the interface, the strong internal electric fields generated at back-to-back heterojunctions can be used for oxide electronics, analogous to bipolar transistors. Here we demonstrate a perovskite heteroepitaxial metal-base transistor operating at room temperature, enabled by interface dipole engineering. Analysis of many devices quantifies the evolution from hot-electron to permeable-base behaviour. This device provides a platform for incorporating the exotic ground states of perovskite oxides, as well as novel electronic phases at their interfaces.

  16. Improving biological relevancy of transcriptional biomarkers experiments by applying the MIQE guidelines to pre-clinical and clinical trials.

    PubMed

    Dooms, M; Chango, A; Barbour, E; Pouillart, P; Abdel Nour, A M

    2013-01-01

    The "Minimum Information for the Publication of qPCR Experiments" (MIQE [3]) guidelines are very much targeted at basic research experiments and have to our knowledge not been applied to qPCR assays carried out in the context of clinical trials. This report details the use of the MIQE qPCR app for iPhone (App Store, Apple) to assess the MIQE compliance of one clinical and five pre-clinical trials. This resulted in the need to include 14 modifications that make the guidelines more relevant for the assessment of this special type of application. We also discuss the need for flexibility, since while some parameters increase experimental quality, they also require more reagents and more time, which is not always feasible in a clinical setting. PMID:22910527

  17. Emotional interference-based forgetting in short-term memory. Cognitive inhibition of pleasant but not unpleasant biologically relevant distractors

    PubMed Central

    García-Pacios, Javier; Del Río, David; Villalobos, Dolores; Ruiz-Vargas, José M.; Maestú, Fernando

    2015-01-01

    Emotional stimuli automatically recruit attentional resources. Although this usually brings more adaptive responses, it may suppose a disadvantage when emotional information is task-irrelevant and should be ignored. Previous studies have shown how emotional stimuli with a negative content exert a greater interference than neutral stimuli during a concurrent working memory (WM) task. However, the impact of positively valenced stimuli as interference has not been addressed to date. In three experiments and one re-analysis we explore the impact of pleasant and unpleasant emotional distractors during WM maintenance. The results suggest that our cognitive control can cope with the interference posed by pleasant distractors as well as with the interference posed by neutral stimuli. However, unpleasant distractors are harder to control in the context of WM maintenance. As unpleasant stimuli usually convey relevant information that we should not to ignore, our executive control seems to be less able to reallocate cognitive resources after unpleasant distraction. PMID:25999894

  18. Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

    PubMed

    Appel, T; Bierhoff, E; Appel, K; von Lindern, J-J; Bergé, S; Niederhagen, B

    2003-06-01

    We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours. PMID:12804537

  19. Biological Production of a Hydrocarbon Fuel Intermediate Polyhydroxybutyrate (PHB) from a Process Relevant Lignocellulosic Derived Sugar (Poster)

    SciTech Connect

    Wang, W.; Mittal, A.; Mohagheghi, A.; Johnson, D. K.

    2014-04-01

    PHAs are synthesized by many microorganisms to serve as intracellular carbon storage molecules. In some bacterial strains, PHB can account for up to 80% of cell mass. In addition to its application in the packaging sector, PHB also has great potential as an intermediate in the production of hydrocarbon fuels. PHB can be thermally depolymerized and decarboxylated to propene which can be upgraded to hydrocarbon fuels via commercial oligomerization technologies. Cupriavidus necator is the microorganism that has been most extensively studied and used for PHB production on an industrial scale; However the substrates used for producing PHB are mainly fructose, glucose, sucrose, fatty acids, glycerol, etc., which are expensive. In this study, we demonstrate production of PHB from a process relevant lignocellulosic derived sugar stream, i.e., saccharified slurry from pretreated corn stover. The strain was first investigated in shake flasks for its ability to utilize glucose, xylose and acetate. In addition, the strain was also grown on pretreated lignocellulose hydrolyzate slurry and evaluated in terms of cell growth, sugar utilization, PHB accumulation, etc. The mechanism of inhibition in the toxic hydrolysate generated by the pretreatment and saccharification process of biomass, was also studied.

  20. The nonconservative property of dissolved molybdenum in the western Taiwan Strait: Relevance of submarine groundwater discharges and biological utilization

    NASA Astrophysics Data System (ADS)

    Wang, Deli; Xia, Weiwei; Lu, Shuimiao; Wang, Guizhi; Liu, Qian; Moore, Willard S.; Arthur Chen, Chen-Tung

    2016-01-01

    This study examined dissolved Mo and sedimentary Mo along with hydrochemical parameters in the western Taiwan Strait (WTS) in May and August 2012. The results demonstrate that dissolved Mo could be depleted of as high as 10-20 nM during our May sampling period when the nutrient-enriched Min-Zhe coastal current ceased and spring blooms developed. The negative correlation between Chl-a and dissolved Mo suggests the possible involvement of high algal productivity in removing dissolved Mo out of the water column. Specific oceanographic settings (little currents) permitted a high sedimentary enrichment of Mo (>6 µg/g Mo) within the highly productive waters outside the Jiulong River mouth. Possibly, the high algal productivities and consequent organic matter sinks provide a pathway of Mo burial from water columns into sediments. Dissolved Mo was relatively high in groundwater samples, but we observed that submarine groundwater discharges (SGDs) only contributed to a relatively small percentage of the total dissolved Mo pool in WTS. It is probably attributable to the immediate removal of SGD-released Mo ions via adsorption onto newly formed Mn oxides once exposed to oxygenated seawater, followed by an elevated sedimentary Mo accumulation near the SGDs (˜5 µg/g). In addition to metal oxide particle scavenging and sulfide precipitation, we estimated that biological uptake along with Mo adsorption onto organic matter carriers could finally provide more than 10% of the annual sedimentary Mo accumulation in WTS.

  1. Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data.

    PubMed

    De Cecco, Loris; Nicolau, Monica; Giannoccaro, Marco; Daidone, Maria Grazia; Bossi, Paolo; Locati, Laura; Licitra, Lisa; Canevari, Silvana

    2015-04-20

    Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40-50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets. Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes. To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies. PMID:25821127

  2. Relevance of Hydrodynamic Effects for the Calculation of Outer Surface Potential of Biological Membrane Using Electrophoretic Data.

    PubMed

    Silva, Izan M; Castro, Maria Clícia S; Silva, Dilson; Cortez, Célia M

    2016-06-01

    In this paper, we present the results of a study on the influence of hydrodynamic effects on the surface potentials of the erythrocyte membrane, comparing two different models formulated to simulate the electrophoretic movement of a biological cell: the classical Helmholtz-Smoluchowski model and a model presented by Hsu et al. (1996). This model considers hydrodynamic effects to describe the distribution of the fluid velocity. The electric potential equation was obtained from the non-linear Poisson-Boltzmann equation, considering the spatial distribution of electrical charges fixed in glycocalyx and cytoplasmic proteins, as well as electrolyte charges and ones fixed on the surfaces of lipidic bilayer. Our results show that the Helmholtz-Smoluchowski model is not able to reflect the real forces responsible to the electrophoretic behavior of cell, because it does not take account the hydrodynamic effects of glycocalyx. This charged network that covers cellular surface constitutes a complex physical system whose electromechanical characteristics cannot be neglected. Then, supporting the hypothesis of other authors, we suggest that, in electrophoretic motion analyses of cells, the classical model represents a limiting case of models that take into account hydrodynamic effects to describe the velocity distribution of fluid. PMID:27276378

  3. Identification of Genes Relevant to Pesticides and Biology from Global Transcriptome Data of Monochamus alternatus Hope (Coleoptera: Cerambycidae) Larvae

    PubMed Central

    Shao, Ensi; Rebeca, Carballar-Lejarazú; Guo, Yajie; Xiong, Yueting; Mou, Yani; Xu, Runxue; Hu, Xia; Liang, Guanghong; Zou, Shuangquan; Guan, Xiong; Zhang, Feiping

    2016-01-01

    Monochamus alternatus Hope is the main vector in China of the Pine Wilt Disease caused by the pine wood nematode Bursaphelenchus xylophilus. Although chemical control is traditionally used to prevent pine wilt disease, new strategies based in biological control are promising ways for the management of the disease. However, there is no deep sequence analysis of Monochamus alternatus Hope that describes the transcriptome and no information is available about gene function of this insect vector. We used next generation sequencing technology to sequence the whole fourth instar larva transcriptome of Monochamus alternatus Hope and successfully built a Monochamus alternatus Hope transcriptome database. In total, 105,612 unigenes were assigned for Gene Ontology (GO) terms, information for 16,730 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs) database, and 13,024 unigenes matched with 224 predicted pathways in the Kyoto Encyclopedia of Genes and Genome (KEGG). In addition, genes related to putative insecticide resistance-related genes, RNAi, the Bt receptor, intestinal digestive enzymes, possible future insect control targets and immune-related molecules are described. This study provides valuable basic information that can be used as a gateway to develop new molecular tools for Monochamus alternatus Hope control strategies. PMID:26815657

  4. Identification of Genes Relevant to Pesticides and Biology from Global Transcriptome Data of Monochamus alternatus Hope (Coleoptera: Cerambycidae) Larvae.

    PubMed

    Wu, Songqing; Zhu, Xiaoli; Liu, Zhaoxia; Shao, Ensi; Rebeca, Carballar-Lejarazú; Guo, Yajie; Xiong, Yueting; Mou, Yani; Xu, Runxue; Hu, Xia; Liang, Guanghong; Zou, Shuangquan; Guan, Xiong; Zhang, Feiping

    2016-01-01

    Monochamus alternatus Hope is the main vector in China of the Pine Wilt Disease caused by the pine wood nematode Bursaphelenchus xylophilus. Although chemical control is traditionally used to prevent pine wilt disease, new strategies based in biological control are promising ways for the management of the disease. However, there is no deep sequence analysis of Monochamus alternatus Hope that describes the transcriptome and no information is available about gene function of this insect vector. We used next generation sequencing technology to sequence the whole fourth instar larva transcriptome of Monochamus alternatus Hope and successfully built a Monochamus alternatus Hope transcriptome database. In total, 105,612 unigenes were assigned for Gene Ontology (GO) terms, information for 16,730 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs) database, and 13,024 unigenes matched with 224 predicted pathways in the Kyoto Encyclopedia of Genes and Genome (KEGG). In addition, genes related to putative insecticide resistance-related genes, RNAi, the Bt receptor, intestinal digestive enzymes, possible future insect control targets and immune-related molecules are described. This study provides valuable basic information that can be used as a gateway to develop new molecular tools for Monochamus alternatus Hope control strategies. PMID:26815657

  5. Toward Relatively General and Accurate Quantum Chemical Predictions of Solid-State 17O NMR Chemical Shifts in Various Biologically Relevant Oxygen-containing Compounds

    PubMed Central

    Rorick, Amber; Michael, Matthew A.; Yang, Liu; Zhang, Yong

    2015-01-01

    Oxygen is an important element in most biologically significant molecules and experimental solid-state 17O NMR studies have provided numerous useful structural probes to study these systems. However, computational predictions of solid-state 17O NMR chemical shift tensor properties are still challenging in many cases and in particular each of the prior computational work is basically limited to one type of oxygen-containing systems. This work provides the first systematic study of the effects of geometry refinement, method and basis sets for metal and non-metal elements in both geometry optimization and NMR property calculations of some biologically relevant oxygen-containing compounds with a good variety of XO bonding groups, X= H, C, N, P, and metal. The experimental range studied is of 1455 ppm, a major part of the reported 17O NMR chemical shifts in organic and organometallic compounds. A number of computational factors towards relatively general and accurate predictions of 17O NMR chemical shifts were studied to provide helpful and detailed suggestions for future work. For the studied various kinds of oxygen-containing compounds, the best computational approach results in a theory-versus-experiment correlation coefficient R2 of 0.9880 and mean absolute deviation of 13 ppm (1.9% of the experimental range) for isotropic NMR shifts and R2 of 0.9926 for all shift tensor properties. These results shall facilitate future computational studies of 17O NMR chemical shifts in many biologically relevant systems, and the high accuracy may also help refinement and determination of active-site structures of some oxygen-containing substrate bound proteins. PMID:26274812

  6. Detailed characterization of mechanical properties and molecular mobility within dry seed glasses: relevance to the physiology of dry biological systems.

    PubMed

    Ballesteros, Daniel; Walters, Christina

    2011-11-01

    Slow movement of molecules in glassy matrices controls the kinetics of chemical and physical reactions in dry seeds. Variation in physiological activity among seeds suggests that there are differences in mobility among seed glasses. Testing this hypothesis is difficult because few tools are available to measure molecular mobility within dry seeds. Here, motional properties within dry pea cotyledons were assessed using dynamic mechanical analysis. The technique detected several molecular relaxations between -80 and +80°C and gave a more detailed description of water content-temperature effects on molecular motion than previously understood from studies of glass formation in seeds at glass transition (Tg). Diffusive movement is delimited by the α relaxation, which appears to be analogous to Tg. β and γ relaxations were also detected at temperatures lower than α relaxations, clearly demonstrating intramolecular motion within the glassy matrix of the pea cotyledon. Glass transitions, or the mechanical counterpart α relaxation, appear to be less relevant to seed aging during dry storage than previously thought. On the other hand, β relaxation occurs at temperature and moisture conditions typically used for seed storage and has established importance for physical aging of synthetic polymer glasses. Our data show that the nature and extent of molecular motion varies considerably with moisture and temperature, and that the hydrated conditions used for accelerated aging experiments and ultra-dry conditions sometimes recommended for seed storage give greater molecular mobility than more standard seed storage practices. We believe characterization of molecular mobility is critical for evaluating how dry seeds respond to the environment and persist through time. PMID:21831210

  7. Biological Networks for Predicting Chemical Hepatocarcinogenicity Using Gene Expression Data from Treated Mice and Relevance across Human and Rat Species

    PubMed Central

    Thomas, Reuben; Thomas, Russell S.; Auerbach, Scott S.; Portier, Christopher J.

    2013-01-01

    Background Several groups have employed genomic data from subchronic chemical toxicity studies in rodents (90 days) to derive gene-centric predictors of chronic toxicity and carcinogenicity. Genes are annotated to belong to biological processes or molecular pathways that are mechanistically well understood and are described in public databases. Objectives To develop a molecular pathway-based prediction model of long term hepatocarcinogenicity using 90-day gene expression data and to evaluate the performance of this model with respect to both intra-species, dose-dependent and cross-species predictions. Methods Genome-wide hepatic mRNA expression was retrospectively measured in B6C3F1 mice following subchronic exposure to twenty-six (26) chemicals (10 were positive, 2 equivocal and 14 negative for liver tumors) previously studied by the US National Toxicology Program. Using these data, a pathway-based predictor model for long-term liver cancer risk was derived using random forests. The prediction model was independently validated on test sets associated with liver cancer risk obtained from mice, rats and humans. Results Using 5-fold cross validation, the developed prediction model had reasonable predictive performance with the area under receiver-operator curve (AUC) equal to 0.66. The developed prediction model was then used to extrapolate the results to data associated with rat and human liver cancer. The extrapolated model worked well for both extrapolated species (AUC value of 0.74 for rats and 0.91 for humans). The prediction models implied a balanced interplay between all pathway responses leading to carcinogenicity predictions. Conclusions Pathway-based prediction models estimated from sub-chronic data hold promise for predicting long-term carcinogenicity and also for its ability to extrapolate results across multiple species. PMID:23737943

  8. Intra-specific variability and biological relevance of P3N-PIPO protein length in potyviruses

    PubMed Central

    2013-01-01

    Background Pipo was recently described as a new ORF encoded within the genome of the Potyviridae family members (PNAS 105:5897–5902, 2008). It is embedded within the P3 cistron and is translated in the +2 reading frame relative to the potyviral long ORF as the P3N-PIPO fusion protein. In this work, we first collected pipo nucleotide sequences available for different isolates of 48 Potyvirus species. Second, to determine the biological implications of variation in pipo length, we measured infectivity, viral accumulation, cell-to-cell and systemic movements for two Turnip mosaic virus (TuMV) variants with pipo alleles of different length in three different susceptible host species, and tested for differences between the two variants. Results In addition to inter-specific variation, there was high variation in the length of the PIPO protein among isolates within species (ranging from 1 to 89 amino acids). Furthermore, selection analyses on the P3 cistron did not account for the existence of stop codons in the pipo ORF, but showed that positive selection was significant in the overlapping region for Potato virus Y (PVY) and TuMV. In some cases, variability in length was associated with host species, geographic provenance and/or other strain features. We found significant empirical differences among the phenotypes associated with TuMV pipo alleles, though the magnitude and sign of the effects were host-dependent. Conclusions The combination of computational molecular evolution analyses and experiments stemming from these analyses provide clues about the selective pressures acting upon the different-length pipo alleles and show that variation in length may be maintained by host-driven selection. PMID:24225158

  9. A multicomponent bioactive tissue-engineered blood vessel: Fabrication, mechanical evaluation and biological evaluation with physiological-relevant conditions

    NASA Astrophysics Data System (ADS)

    Bonani, Walter

    The high long-term failure rate of synthetic vascular grafts in the replacement of small vessels is known to be associated with the lack of physiological signals to vascular cells causing adverse hemodynamic, inflammatory or coagulatory events. Current studies focus on developing engineered vascular devices with ability of directing cell activity in vitro and in vivo for tissue regeneration. It is also known that controlled molecule release from scaffolds can dramatically increase the scaffold ability of directing cell activities in vitro and in vivo for tissue regeneration. To address the mechanical and biological problems associated with graft materials, we demonstrated a degradable polyester-fibroin composite tubular scaffolds which shows well-integrated nanofibrous structure, endothelial-conducive surface and anisotropic mechanical property, suitable as engineered vascular constructs. Tissue regeneration needs not only functional biomolecules providing signaling cues to cells and guide tissue remodeling, but also an adequate modality of molecule delivery. In fact, healthy tissue formation requires specific signals at well-defined place and time. To develop scaffolds with multi-modal presentation of biomolecules, we patterned electrospun nanofibers over the thickness of the 3-dimensional scaffolds by programming the deposition of interpenetrating networks of degradable polymers poly(a-caprolactone) and poly(lactide-co-glycolide) acid in tailored proportion. Fluorescent model molecules, drug and growth factors were embedded in the polymeric fibers with different techniques and release profiles were obtained and discussed. Fabrication process resulted in precise gradient patterns of materials and functional biomolecules throughout the thickness of the scaffold. These graded materials showed programmable spatio-temporal control over the release. Molecule release profiles on each side of the scaffolds were used to determine the separation efficiency of molecule

  10. Synthesis of fluorophore encapsulated silica nanoparticles for the evaluation of the biological fate and toxicity of food relevant nanoparticles

    NASA Astrophysics Data System (ADS)

    Zane, Andrew Paul

    fluorophores, rhodamine 6G and rhodamine 800, into silica shells for direct monitoring in intestinal epithelial cells and tissues of exposed mice. We show that, for small nanoparticles, a typical Stober-type ammonia driven synthesis does not yield stable fluorescence. This has been observed in literature and is attributed to incompletely hydrolyzed silica precursor causing partial dissolution of the silica shell. We remedy this by applying an arginine driven silica shell synthesis, which is known to produce a denser and more stable product at smaller particle sizes. We show that all three fluorophores can be coated in a simple generalized procedure, and the resulting particles all show stable fluorescence with no evidence of dye leakage. Using these particles, we demonstrate that silica nanoparticles can be observed internalizing into C2BBe1 intestinal epithelial cells, and in the tissues of mice that were fed the particles by gavage. We find direct evidence that the particles are absorbed into circulation and subsequently localize in organs throughout the body. Future efforts will attempt to better quantify this accumulation, as well as generalize the procedure to other food relevant nanoparticles such as TiO2.

  11. Insight into the Local Solvent Environment of Biologically Relevant Iron-nitroysl Systems through Two-Dimensional Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Brookes, Jennifer Faith

    Iron-nitrosyl systems, particularly in the form of heme proteins, with their iron metal active sites play an important role in biological systems. Heme proteins act as storage, transporters, and receptors for nitric oxide (NO), a signaling molecule that is important in immune, nervous, and cardiovascular systems of mammals. By better understanding the local environment of the active site of NO binding heme proteins we can gain insight into disease in which the NO pathways have been implicated. This is an important step to being able to develop pharmaceuticals targeting NO pathways in humans. Sodium nitroprusside ((SNP, Na2[Fe(CN)5is NO]·2H 2O) investigated as a model system for the active site of nitric oxide binding heme proteins. Using two-dimensional infrared spectroscopy (2D IR) to obtain dephasing dynamics of the nitrosyl stretch (nuNO) in a series of solvents we are able to better understand the local environment of the more complicated metalloproteins. Rigorous line shape analysis is performed by using nonlinear response theory to simulate 2D IR spectra which are then fit to experimental data in an iterative process to extract frequency-frequency correlation functions (FFCFs). The time scales obtained are then correlated to empirical solvent polarity parameters. The analysis of the 2D IR lineshapes reveal that the spectral diffusion timescale of the nuNO in SNP varies from 0.8 -- 4 ps and is negatively correlated with the empirical solvent polarity scales. We continue to investigate NO binding of metalloproteins through 2D IR experiments on nitrophorin 4 (NP4). NP4 is a pH-sensitive NO transporter protein present in the salivary gland of the blood sucking insect Rhodius prolixus which undergoes a pH sensitive structural change between a closed and open conformation allowing for the storage and delivery of NO. The two structures are observed spectroscopically as two distinct pH-dependent nu NO frequencies at ~1904 and ~1917 cm-1. We obtain FFCFs by globally

  12. Chemometric analysis of correlations between electronic absorption characteristics and structural and/or physicochemical parameters for ampholytic substances of biological and pharmaceutical relevance

    NASA Astrophysics Data System (ADS)

    Judycka-Proma, U.; Bober, L.; Gajewicz, A.; Puzyn, T.; Błażejowski, J.

    2015-03-01

    Forty ampholytic compounds of biological and pharmaceutical relevance were subjected to chemometric analysis based on unsupervised and supervised learning algorithms. This enabled relations to be found between empirical spectral characteristics derived from electronic absorption data and structural and physicochemical parameters predicted by quantum chemistry methods or phenomenological relationships based on additivity rules. It was found that the energies of long wavelength absorption bands are correlated through multiparametric linear relationships with parameters reflecting the bulkiness features of the absorbing molecules as well as their nucleophilicity and electrophilicity. These dependences enable the quantitative analysis of spectral features of the compounds, as well as a comparison of their similarities and certain pharmaceutical and biological features. Three QSPR models to predict the energies of long-wavelength absorption in buffers with pH = 2.5 and pH = 7.0, as well as in methanol, were developed and validated in this study. These models can be further used to predict the long-wavelength absorption energies of untested substances (if they are structurally similar to the training compounds).

  13. Development of metal based thermal barrier coatings

    NASA Astrophysics Data System (ADS)

    Shin, Dong-Il

    In this work, metal-based thermal barrier coatings (MBTBCs) have been produced, using high frequency induction plasma spraying (IPS) of iron-based nanostructured alloy powders. Important advances have been made over recent years to the development of ceramic-based thermal barrier coatings (TBCs) for internal combustion engines application, but they are not yet applied in mass production situations. Besides the important economic considerations, the reliability of ceramic: TBCs is also an issue, being associated with the difficulty of predicting their "in-service" lifetime. Through engineering of the nano/amorphous structure of MBTBCs, their thermal conductivity can be made as low as those of ceramic-based TBCs, with reduced mean free paths of the electrons/phonons scattering. In this work, nano/amorphous structured coatings were deposited by IPS using the following spray parameters: spraying distance (210 ˜ 270 mm), plasma gas composition (Ar/N2), IPS torch power (24kW), and powder feed-rate (16g/min.). The structure and properties of the deposited layers were characterized through SEM (Scanning Electron Microscopy) observations. The thermal diffusivity (alpha) properties of the MBTBCs were measured using a laser flash method. Density (rho) and specific heat (Cp) of the MBTBCs were also measured, and their thermal conductivity (k) calculated (k =alpharhoCp). The thermal conductivity of MBTBCs was found to be as low as 1.99 W/m/K. The heat treatment study showed that crystal structure changes, and grain size growth from a few nanometers to tenth of nanometers occurred at 550°C under static exposure conditions. Thermal expansion coefficient (TEC) of MBTBCs was 13E-6/K, which is close to the TEC of cast iron and thus, closer to the TEC values of aluminium alloys than are conventional TBCs. Fracture toughness of MBTBCs has also been assessed by use of Vickers hardness tests, with a 500 g load for 15 s, and the results show that there are no measurable crack

  14. Making Biology Relevant to Undergraduates

    ERIC Educational Resources Information Center

    Musante, Susan

    2012-01-01

    This article features Science Education for New Civic Engagements and Responsibilities (SENCER; www.sencer.net) Summer Institute. The SENCER program, which began formally in 2001, was the vision of David Burns; Karen Oates, currently Peterson Family Dean of Arts and Sciences at Worcester Polytechnic Institute; and Ric Wiebl, currently director of…

  15. Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Mehinto, Alvine C; Hill, Elizabeth M; Tyler, Charles R

    2010-03-15

    Diclofenac, a nonsteroidal anti-inflammatory drug, is widely detected in surface waters and can potentially cause deleterious effects in fish. Here, we investigated the biological effects of 21-day exposure to waterborne diclofenac at environmentally relevant concentrations (0, 0.5, 1, 5, and 25 μg/L) in rainbow trout Accumulation of diclofenac in the bile was measured and responses in selected tissues were assessed via changes in the expression of selected genes (cytochrome P450 (cyp) 1a1, cyclooxygenase (cox) 1 and 2, and p53) involved in metabolism of xenobiotics, prostaglandin synthesis, and cell cycle control, respectively, together with histopathological alterations in these tissues. Diclofenac accumulated in the bile by a factor of between 509 ± 27 and 657 ± 25 and various metabolites were putatively identified as hydroxydiclofenac, diclofenac methyl ester, and the potentially reactive metabolite hydroxydiclofenac glucuronide. Expression levels of both cox1 and cox2 in liver, gills, and kidney were significantly reduced by diclofenac exposure from only 1 μg/L. Expression of cyp1a1 was induced in the liver and the gills but inhibited in the kidney of exposed fish. Diclofenac exposure induced tubular necrosis in the kidney and hyperplasia and fusion of the villi in the intestine from 1 μg/L. This study demonstrates that subchronic exposure to environmental concentrations of diclofenac can interfere with the biochemical functions of fish and lead to tissue damage, highlighting further the concern about this pharmaceutical in the aquatic environment. PMID:20175546

  16. geneCommittee: a web-based tool for extensively testing the discriminatory power of biologically relevant gene sets in microarray data classification

    PubMed Central

    2014-01-01

    Background The diagnosis and prognosis of several diseases can be shortened through the use of different large-scale genome experiments. In this context, microarrays can generate expression data for a huge set of genes. However, to obtain solid statistical evidence from the resulting data, it is necessary to train and to validate many classification techniques in order to find the best discriminative method. This is a time-consuming process that normally depends on intricate statistical tools. Results geneCommittee is a web-based interactive tool for routinely evaluating the discriminative classification power of custom hypothesis in the form of biologically relevant gene sets. While the user can work with different gene set collections and several microarray data files to configure specific classification experiments, the tool is able to run several tests in parallel. Provided with a straightforward and intuitive interface, geneCommittee is able to render valuable information for diagnostic analyses and clinical management decisions based on systematically evaluating custom hypothesis over different data sets using complementary classifiers, a key aspect in clinical research. Conclusions geneCommittee allows the enrichment of microarrays raw data with gene functional annotations, producing integrated datasets that simplify the construction of better discriminative hypothesis, and allows the creation of a set of complementary classifiers. The trained committees can then be used for clinical research and diagnosis. Full documentation including common use cases and guided analysis workflows is freely available at http://sing.ei.uvigo.es/GC/. PMID:24475928

  17. A handy liquid metal based electroosmotic flow pump.

    PubMed

    Gao, Meng; Gui, Lin

    2014-06-01

    A room temperature liquid metal based electroosmotic flow (EOF) pump has been proposed in this work. This low-cost EOF pump is convenient for both fabrication and integration. It utilizes polydimethylsiloxane (PDMS) microchannels filled with the liquid-metal as non-contact pump electrodes. The electrode channels are fabricated symmetrically to both sides of the pumping channel, having no contact with the pumping channel. To test the pumping performance of the EOF pump, the mean flow velocities of the fluid (DI water) in the EOF pumps were experimentally measured by tracing the fluorescent microparticles in the flow. To provide guidance for designing a low voltage EOF pump, parametric studies on dimensions of the electrode and pumping channels were performed in this work. According to the experimental results, the pumping speed can reach 5.93 μm s(-1) at a driving voltage of only 1.6 V, when the gap between the electrode and the pumping channel is 20 μm. Injecting a room temperature liquid metal into microchannels can provide a simple, rapid, low-cost but accurately self-aligned way to fabricate microelectrodes for EOF pumps, which is a promising method to achieve the miniaturization and integration of the EOF pump in microfluidic systems. The non-contact liquid electrodes have no influence on the fluid in the pumping channel when pumping, reducing Joule heat generation and preventing gas bubble formation at the surface of electrodes. The pump has great potential to drive a wide range of fluids, such as drug reagents, cell suspensions and biological macromolecule solutions. PMID:24706096

  18. Engineered metal based nanoparticles and innate immunity.

    PubMed

    Petrarca, Claudia; Clemente, Emanuela; Amato, Valentina; Pedata, Paola; Sabbioni, Enrico; Bernardini, Giovanni; Iavicoli, Ivo; Cortese, Sara; Niu, Qiao; Otsuki, Takemi; Paganelli, Roberto; Di Gioacchino, Mario

    2015-01-01

    Almost all people in developed countries are exposed to metal nanoparticles (MeNPs) that are used in a large number of applications including medical (for diagnostic and therapeutic purposes). Once inside the body, absorbed by inhalation, contact, ingestion and injection, MeNPs can translocate to tissues and, as any foreign substance, are likely to encounter the innate immunity system that represent a non-specific first line of defense against potential threats to the host. In this review, we will discuss the possible effects of MeNPs on various components of the innate immunity (both specific cells and barriers). Most important is that there are no reports of immune diseases induced by MeNPs exposure: we are operating in a safe area. However, in vitro assays show that MeNPs have some effects on innate immunity, the main being toxicity (both cyto- and genotoxicity) and interference with the activity of various cells through modification of membrane receptors, gene expression and cytokine production. Such effects can have both negative and positive relevant impacts on humans. On the one hand, people exposed to high levels of MeNPs, as workers of industries producing or applying MeNPs, should be monitored for possible health effects. On the other hand, understanding the modality of the effects on immune responses is essential to develop medical applications for MeNPs. Indeed, those MeNPs that are able to stimulate immune cells could be used to develop of new vaccines, promote immunity against tumors and suppress autoimmunity. PMID:26180517

  19. Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation-independent manner

    PubMed Central

    Pérez-Torras, S; Vidal-Pla, A; Cano-Soldado, P; Huber-Ruano, I; Mazo, A; Pastor-Anglada, M

    2013-01-01

    Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs have specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP-ribose) polymerase hyperactivation and cell death and reduced cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. Moreover, this study also shows that restoration of hCNT1 expression is able to reduce tumor growth in a mouse model of pancreatic adenocarcinoma. These data predict a novel role for a NT protein, hCNT1, which appears to be independent of its role as mediator of nucleoside uptake by cells. Thereby, hCNT1 fits the profile of a transceptor in a substrate translocation-independent manner and is likely to be relevant to tumor biology. PMID:23722537

  20. Discovery of Anti-inflammatory Ingredients in Chinese Herbal Formula Kouyanqing Granule based on Relevance Analysis between Chemical Characters and Biological Effects.

    PubMed

    Liu, Hong; Zheng, Yan-fang; Li, Chu-yuan; Zheng, Yu-ying; Wang, De-qin; Wu, Zhong; Huang, Lin; Wang, Yong-gang; Li, Pei-bo; Peng, Wei; Su, Wei-wei

    2015-01-01

    Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson's correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role. PMID:26657159

  1. Accessing a Biologically Relevant Benzofuran Skeleton by a One-Pot Tandem Heck Alkynylation/Cyclization Reaction Using Well-Defined Palladium N-Heterocyclic Carbene Complexes.

    PubMed

    Kumar, Anuj; Gangwar, Manoj Kumar; Prakasham, A P; Mhatre, Darshan; Kalita, Alok Ch; Ghosh, Prasenjit

    2016-03-21

    Well-defined palladium N-heterocyclic carbene (NHC) complexes were employed in the one-pot tandem Heck alkynylation/cyclization sequence for preparing biologically relevant benzofuran compounds under copper-free conditions in a time-efficient step-reduced fashion. In particular, a series of binuclear palladium complexes, 1b-1e and 2b-2e, of the alkyl-bridged NHC ligands, namely, {1,1'-di-R1-4,4'-R2-di-1,2,4-triazoline-5,5'-diylid-2-ene] (R1 = i-Pr; R2 = -(CH2)2-, -(CH2)3-), and their mononuclear analogues, trans-(NHC)PdBr2(pyridine) (3b) and cis-(NHC)PdBr2(PPh3) (3c), successfully catalyzed the one-pot tandem Heck alkynylation/cyclization reaction of 2-iodophenol with a variety of terminal alkyne substrates, yielding 2-substituted benzofuran derivatives. The mononuclear complexes 3b and 3c were nearly half as active as the representative dinuclear analogue 1c under analogous reaction conditions, thereby implying that, at the same mole percent of the palladium loading, the monometallic 3b and 3c and the bimetallic 1c complexes were equally effective as catalysts. The two sites of the bimetallic complex 1c performed as two separate independent catalytic sites, displaying no cooperativity effect in the catalysis. Finally, the practical utility of the aforementioned catalysts was demonstrated for a representative catalyst 1c through the convenient synthesis of a key intermediate, 3-[2-(benzo[d][1,3]dioxol-5-yl)-7-methoxybenzofuran-5-yl]propan-1-ol, in a total-synthesis protocol of the natural product Egonol. PMID:26928799

  2. Discovery of Anti-inflammatory Ingredients in Chinese Herbal Formula Kouyanqing Granule based on Relevance Analysis between Chemical Characters and Biological Effects

    PubMed Central

    Liu, Hong; Zheng, Yan-fang; Li, Chu-yuan; Zheng, Yu-ying; Wang, De-qin; Wu, Zhong; Huang, Lin; Wang, Yong-gang; Li, Pei-bo; Peng, Wei; Su, Wei-wei

    2015-01-01

    Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson’s correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role. PMID:26657159

  3. Relevancy 101

    NASA Technical Reports Server (NTRS)

    Lynnes, Chris; Newman, Doug

    2016-01-01

    Where we present an overview on why relevancy is a problem, how important it is and how we can improve it. The topic of relevancy is becoming increasingly important in earth data discovery as our audience is tuned to the accuracy of standard search engines like Google.

  4. Bioinspired nanoreactors for the biomineralisation of metallic-based nanoparticles for nanomedicine.

    PubMed

    Bain, Jennifer; Staniland, Sarah S

    2015-06-28

    This review explores the synthesis of inorganic metallic-based nanoparticles (MBNPs) (metals, alloys, metal oxides) using biological and biologically inspired nanoreactors for precipitation/crystallisation. Such nanoparticles exhibit a range of nanoscale properties such as surface plasmon resonance (nobel metals e.g. Au), fluorescence (semiconductor quantum dots e.g. CdSe) and nanomagnetism (magnetic alloys e.g. CoPt and iron oxides e.g. magnetite), which are currently the subject of intensive research for their applicability in diagnostic and therapeutic nanomedicine. For such applications, MBNPs are required to be biocompatible, of a precise size and shape for a consistent signal or output and be easily modified with biomolecules for applications. Ideally the MBNPs would be obtained via an environmentally-friendly synthetic route. A biological or biologically inspired nanoreactor synthesis of MBNPs is shown to address these issues. Biological nanoreactors for crystallizing MBNPs within cells (magnetosomes), protein cages (ferritin) and virus capsids (cowpea chlorotic mottle, cowpea mosaic and tobacco mosaic viruses), are discussed along with how these have been modified for applications and for the next generation of new materials. Biomimetic liposome, polymersome and even designed self-assembled proteinosome nanoreactors are also reviewed for MBNP crystallisation and further modification for applications. With the advent of synthetic biology, the research and understanding in this field is growing, with the goal of realising nanoreactor synthesis of MBNPs for biomedical applications within our grasp in the near future. PMID:25865599

  5. Designing and engineering metal-based nanocomposites for nanotechnological applications

    NASA Astrophysics Data System (ADS)

    Bryan, William W.

    Metal-based nanocomposites are extremely versatile materials that can be fabricated to produce various desired responses (e.g. magnetic, optical, catalytic, mechanical, electric, and thermal). Because of their large surface-to-volume ratio, metal-based nanocomposites are unique materials that yield properties significantly different from those of bulk materials. Our research focuses on the design, synthesis, and characterization of metal-based nanocomposites utilizing various self-assembly and wet-chemical techniques. To this end, we have established several different synthetic methods for preparing metal-based nanocomposites. These metal-based nanocomposites are ideally suited for future nanotechnological applications. We report the preparation of small THPC silver, platinum, and palladium nanoparticles with diameters typically ≤ 4 nm using simple wet-chemical methods that employed THPC as the reducing agent. The dimensions of the metal nanoparticles were varied systematically by adjusting the concentration of the reactants. The THPC moieties were bound loosely to the surface of the nanoparticles and could be readily removed by centrifugation/washing. The availability of the THPC-metal nanoparticles, allowed the reliable preparation of silver, platinum, and palladium metal nanoshells. The use of a seeded-growth method facilitates the growth of pure metal nanoshells. The facile methods carried out describing nanoshell preparation, as well as the nanoshells themselves will likely supplement or replace existing nanoshells and methods of nanoshell fabrication. We extended these methodologies by demonstrating the reliable preparation of gold-coated magnetic nanoparticles using molecular self-assembly and colloidal growth chemistry. The methods described enable the reliable synthesis of core-shell nanoparticles having dimensions of ˜200 nm in total diameter. Furthermore, we demonstrated that these gold-coated magnetic nanoparticles can be coated with thin hydrogel

  6. Density functional theory estimation of isotope fractionation of Fe, Ni, Cu, and Zn among species relevant to geochemical and biological environments

    NASA Astrophysics Data System (ADS)

    Fujii, Toshiyuki; Moynier, Frédéric; Blichert-Toft, Janne; Albarède, Francis

    2014-09-01

    This paper reports the values of reduced partition function ratios (as 1000 ln β) for Fe, Ni, Cu, and Zn bound to a number of inorganic and organic ligands. We used Density Functional Techniques to update the existing data and calculate ln β for new ligands. This work allows for the mass-dependent isotope fractionation to be predicted for various inorganic (hydrated cation, hydroxide, chloride, sulfate, sulfide, phosphate) and organic (citrate, amino acid) complexes of Fe, Ni, Cu, and Zn. Isotope fractionation among coexisting complexes of these metals was evaluated from the ln β values in a variety of geochemical and biological environments. The results provide a framework for interpretation of isotope fractionation observed in seawater and chemical sediments, in the roots and aerial parts of plants, and among the organs and body fluids of mammals.

  7. Extraction and analysis methods for the determination of pyrethroid insecticides in surface water, sediments and biological tissues at environmentally relevant concentrations.

    PubMed

    Mekebri, A; Crane, D B; Blondina, G J; Oros, D R; Rocca, J L

    2008-05-01

    The aim of this study was to develop and validate chemical methods for measuring pyrethroid insecticides at environmentally relevant concentrations in different matrices. The analytes included six synthetic pyrethroids with the highest agricultural and commercial structural uses in California: bifenthrin, cyfluthrin, cypermethrin, esfenvalerate/fenvalerate, lambda-cyhalothrin, permethrin, and their corresponding stereoisomers, which includes enantiomers, diastereomers and racemic mixtures. Fortified water samples were extracted for analysis of synthetic pyrethroids using liquid-liquid extraction, while fortified sediment and fish tissue samples were extracted using pressurized fluid extraction followed by gel permeation chromatography (GPC) to remove matrix interferences. A florisil column was used for additional cleanup and fractionation of sediment and tissue extracts. Extracts were analyzed using dual column high resolution gas chromatography with electron capture detection (GC/ECD) and confirmation was obtained with gas chromatography mass spectrometry using a quadrupole ion trap detector in MS-MS mode. Method detection limits (MDLs) have been established for water (1-3 ng/L), sediment (0.5-4 ng/g dry weight) and tissue (1-3 ng/g fresh weight). Mean percent recoveries of fortified blanks and samples ranged from 75 to 115% with relative standard deviation (RSD) values less than 20% for all target compounds. PMID:18369521

  8. Characterization of the bridged hyponitrite complex {[Fe(OEP)](2)(μ-N(2)O(2))}: reactivity of hyponitrite complexes and biological relevance.

    PubMed

    Berto, Timothy C; Xu, Nan; Lee, Se Ryeon; McNeil, Anne J; Alp, E Ercan; Zhao, Jiyong; Richter-Addo, George B; Lehnert, Nicolai

    2014-07-01

    The detoxification of nitric oxide (NO) by bacterial NO reductase (NorBC) represents a paradigm of how NO can be detoxified anaerobically in cells. In order to elucidate the mechanism of this enzyme, model complexes provide a convenient means to assess potential reaction intermediates. In particular, there have been many proposed mechanisms that invoke the formation of a hyponitrite bridge between the heme b3 and nonheme iron (FeB) centers within the NorBC active site. However, the reactivity of bridged iron hyponitrite complexes has not been investigated much in the literature. The model complex {[Fe(OEP)]2(μ-N2O2)} offers a unique opportunity to study the electronic structure and reactivity of such a hyponitrite-bridged complex. Here we report the detailed characterization of {[Fe(OEP)]2(μ-N2O2)} using a combination of IR, nuclear resonance vibrational spectroscopy, electron paramagnetic resonance, and magnetic circular dichroism spectroscopy along with SQUID magnetometry. These results show that the ground-state electronic structure of this complex is best described as having two intermediate-spin (S = (3)/2) iron centers that are weakly antiferromagnetically coupled across the N2O2(2-) bridge. The analogous complex {[Fe(PPDME)]2(μ-N2O2)} shows overall similar properties. Finally, we report the unexpected reaction of {[Fe(OEP)]2(μ-N2O2)} in the presence and absence of 1-methylimidizole to yield [Fe(OEP)(NO)]. Density functional theory calculations are used to rationalize why {[Fe(OEP)]2(μ-N2O2)} cannot be formed directly by dimerization of [Fe(OEP)(NO)] and why only the reverse reaction is observed experimentally. These results thus provide insight into the general reactivity of hyponitrite-bridged iron complexes with general relevance for the N-N bond-forming step in NorBC. PMID:24971721

  9. Insight into the structural and biological relevance of the T/R transition of the N-terminus of the B-chain in human insulin.

    PubMed

    Kosinová, Lucie; Veverka, Václav; Novotná, Pavlína; Collinsová, Michaela; Urbanová, Marie; Moody, Nicholas R; Turkenburg, Johan P; Jiráček, Jiří; Brzozowski, Andrzej M; Žáková, Lenka

    2014-06-01

    The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin-insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1-B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the "classical" T-state and that a substantial flexibility of the B1-B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin-IR interaction. PMID:24819248

  10. Insight into the Structural and Biological Relevance of the T/R Transition of the N-Terminus of the B-Chain in Human Insulin

    PubMed Central

    2014-01-01

    The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin–insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1–B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the “classical” T-state and that a substantial flexibility of the B1–B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin–IR interaction. PMID:24819248

  11. A paradigm shift in EPH receptor interaction: biological relevance of EPHB6 interaction with EPHA2 and EPHB2 in breast carcinoma cell lines.

    PubMed

    Fox, Brian P; Kandpal, Raj P

    2011-01-01

    EPH receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in axon guidance, tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The varied biological effects of EPH receptors are mediated in part by the expression of these proteins and their intracellular binding proteins. The ability of EPH molecules to form heterodimers within their own class has been suggested, although not exhaustively characterized. We have clarified this phenomenon by showing that EPHB6, a kinase-deficient receptor, can interact with EPHB2 in mammalian cells, and more significantly EPHB6 interacts with EPHA2. However, EPHB6 does not interact with another kinase-deficient receptor, EPHA10. The interaction between EPHB6 and EPHA2 is the first demonstration of an A-type receptor interacting with a B-type receptor. Furthermore, we correlated relative expression of EPHB6, EPHB2 and EPHA2 with non-invasive and invasive phenotypes of breast tumor cell lines. Our results indicate that tumor invasiveness-suppressing activity of EPHB6 is mediated by its ability to sequester other kinase-sufficient and oncogenic EPH receptors. These observations suggest that cellular phenotypes may, in part, be attributed to a combinatorial expression of EPH receptors and heteromeric interactions among the same class, as well as between two classes, of EPH receptors. Our results also suggest that EPHA10 may transduce signals by interacting with other kinase-sufficient receptors in a similar manner. PMID:21737611

  12. An anatomical, histopathological, and molecular biological function study of the fascias posterior to the interperitoneal colon and its associated mesocolon: their relevance to colonic surgery

    PubMed Central

    Gao, Zhidong; Ye, Yingjiang; Zhang, Weiguang; Shen, Danhua; Zhong, Yanfeng; Jiang, Kewei; Yang, Xiaodong; Yin, Mujun; Liang, Bin; Tian, Long; Wang, Shan

    2013-01-01

    The study aim was to explore the anatomy, histopathology, and molecular biological function of the fascias posterior to the interperitoneal colon and its mesocolon to provide information for improving complete mesocolic excision. To accomplish this aim, we performed intraoperative observations in 60 interperitoneal colon-cancer patients accepted for complete mesocolic excision and conducted local anatomy observations for five embalmed cadavers. An additional two embalmed child cadaver specimens were studied with large slices and paraffin sections. Ten of the 60 patients were examined with a lymph node tracer technique in vivo, while fresh specimens from these patients were assessed by histopathological examination and transwell cell migration assays in vitro. The anatomical and histopathological findings showed that the fascias posterior to the interperitoneal colon and its associated mesocolon were composed of two independent layers: the visceral and parietal fascias. These two fascias were primarily composed of collagen fibers, with the parietal fascia containing a small amount of muscle fiber. The in vivo test showed that the visceral fascia surrounded the colon and its associated mesocolon, including vessels and lymphatics, and that it had no lymphatic flow through it into the rear tissues. Moreover, the in vitro assays showed the visceral fascia was able to block tumor cell migration. Although many surgical scholars have known of the existence of fascia tissue posterior to the intraperitoneal colon, the detailed structure has been ignored and been unclear. As shown by our findings, the visceral and parietal fascias are truly formed structures that have not been previously reported. A thorough understanding of fascial structures and the function of the visceral fascia barrier in blocking tumor cells will facilitate surgeons when performing high-quality complete mesocolic excision procedures. PMID:23721400

  13. Selection of appropriate tumour data sets for Benchmark Dose Modelling (BMD) and derivation of a Margin of Exposure (MoE) for substances that are genotoxic and carcinogenic: considerations of biological relevance of tumour type, data quality and uncertainty assessment.

    PubMed

    Edler, Lutz; Hart, Andy; Greaves, Peter; Carthew, Philip; Coulet, Myriam; Boobis, Alan; Williams, Gary M; Smith, Benjamin

    2014-08-01

    This article addresses a number of concepts related to the selection and modelling of carcinogenicity data for the calculation of a Margin of Exposure. It follows up on the recommendations put forward by the International Life Sciences Institute - European branch in 2010 on the application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. The aims are to provide practical guidance on the relevance of animal tumour data for human carcinogenic hazard assessment, appropriate selection of tumour data for Benchmark Dose Modelling, and approaches for dealing with the uncertainty associated with the selection of data for modelling and, consequently, the derived Point of Departure (PoD) used to calculate the MoE. Although the concepts outlined in this article are interrelated, the background expertise needed to address each topic varies. For instance, the expertise needed to make a judgement on biological relevance of a specific tumour type is clearly different to that needed to determine the statistical uncertainty around the data used for modelling a benchmark dose. As such, each topic is dealt with separately to allow those with specialised knowledge to target key areas of guidance and provide a more in-depth discussion on each subject for those new to the concept of the Margin of Exposure approach. PMID:24176677

  14. Mechanism and biological relevance of blue-light (420-453 nm)-induced nonenzymatic nitric oxide generation from photolabile nitric oxide derivates in human skin in vitro and in vivo.

    PubMed

    Opländer, Christian; Deck, Annika; Volkmar, Christine M; Kirsch, Michael; Liebmann, Jörg; Born, Matthias; van Abeelen, Frank; van Faassen, Ernst E; Kröncke, Klaus-Dietrich; Windolf, Joachim; Suschek, Christoph V

    2013-12-01

    Human skin contains photolabile nitric oxide (NO) derivates such as nitrite and S-nitrosothiols, which upon UVA radiation decompose under high-output NO formation and exert NO-specific biological responses such as increased local blood flow or reduced blood pressure. To avoid the injurious effects of UVA radiation, we here investigated the mechanism and biological relevance of blue-light (420-453 nm)-induced nonenzymatic NO generation from photolabile nitric oxide derivates in human skin in vitro and in vivo. As quantified by chemiluminescence detection (CLD), at physiological pH blue light at 420 or 453 nm induced a significant NO formation from S-nitrosoalbumin and also from aqueous nitrite solutions by a to-date not entirely identified Cu(1+)-dependent mechanism. As detected by electron paramagnetic resonance spectrometry in vitro with human skin specimens, blue light irradiation significantly increased the intradermal levels of free NO. As detected by CLD in vivo in healthy volunteers, irradiation of human skin with blue light induced a significant emanation of NO from the irradiated skin area as well as a significant translocation of NO from the skin surface into the underlying tissue. In parallel, blue light irradiation caused a rapid and significant rise in local cutaneous blood flow as detected noninvasively by using micro-light-guide spectrophotometry. Irradiation of human skin with moderate doses of blue light caused a significant increase in enzyme-independent cutaneous NO formation as well as NO-dependent local biological responses, i.e., increased blood flow. The effects were attributed to blue-light-induced release of NO from cutaneous photolabile NO derivates. Thus, in contrast to UVA, blue-light-induced NO generation might be therapeutically used in the treatment of systemic and local hemodynamic disorders that are based on impaired physiological NO production or bioavailability. PMID:24121056

  15. Iron-Clad Fibers: A Metal-Based Biological Strategy for Hard Flexible Coatings

    NASA Astrophysics Data System (ADS)

    Harrington, Matthew J.; Masic, Admir; Holten-Andersen, Niels; Waite, J. Herbert; Fratzl, Peter

    2010-04-01

    The extensible byssal threads of marine mussels are shielded from abrasion in wave-swept habitats by an outer cuticle that is largely proteinaceous and approximately fivefold harder than the thread core. Threads from several species exhibit granular cuticles containing a protein that is rich in the catecholic amino acid 3,4-dihydroxyphenylalanine (dopa) as well as inorganic ions, notably Fe3+. Granular cuticles exhibit a remarkable combination of high hardness and high extensibility. We explored byssus cuticle chemistry by means of in situ resonance Raman spectroscopy and demonstrated that the cuticle is a polymeric scaffold stabilized by catecholato-iron chelate complexes having an unusual clustered distribution. Consistent with byssal cuticle chemistry and mechanics, we present a model in which dense cross-linking in the granules provides hardness, whereas the less cross-linked matrix provides extensibility.

  16. Metal based isatin-derived sulfonamides: their synthesis, characterization, coordination behavior and biological activity.

    PubMed

    Chohan, Zahid H; Supuran, Claudiu T; Ben Hadda, Taibi; Nasim, Faiz-Ul-Hassan; Khan, Khalid M

    2009-06-01

    Some isatin derived sulfonamides and their transition metal [Co(II), Cu(II), Ni(II), Zn(II)] complexes have been synthesized and characterized. The structure of synthesized compounds and their nature of bonding have been inferred on the basis of their physical (magnetic susceptibility and conductivity measurements), analytical (elemental analyses) and spectral (IR, (1)H NMR and (13)C NMR) properties. An octahedral geometry has been suggested for Co(II), Ni(II) and Zn(II) and square-planar for Cu(II) complexes. In order to assess the antibacterial and antifungal behavior, the ligands and their metal(II) complexes were screened for their in vitro antibacterial activity against four Gram-negative species, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi and two Gram-positive species, Staphylococcus aureus and Bacillus subtilis and, for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. In vitro cytotoxic properties of all the compounds were also studied against Artemia salina by brine shrimp bioassay. The results of average antibacterial/antifungal activity showed that zinc(II) complexes were found to be the most active against one or more bacterial/fungal strains as compared to the other metal complexes. PMID:18825557

  17. Metal-based biologically active azoles and β-lactams derived from sulfa drugs.

    PubMed

    Ebrahimi, Hossein Pasha; Hadi, Jabbar S; Almayah, Abdulelah A; Bolandnazar, Zeinab; Swadi, Ali G; Ebrahimi, Amirpasha

    2016-03-01

    Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, (1)H NMR, (13)C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1-2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the β-lactam derivatives (3-4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5-8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands. PMID:26833242

  18. Metal-based biologically active compounds: synthesis, characterization, DNA interaction, antibacterial, cytotoxic and SOD mimic activities.

    PubMed

    Patel, Mohan N; Patel, Chintan R; Joshi, Hardik N

    2013-02-01

    The square pyramidal copper(II) complexes of N, O- donor ligand and ciprofloxacin have been synthesized. Synthesized complexes were characterized by physicochemical parameters like elemental analysis, electronic, FT-IR and LC-MS spectra. The complexes were screened for their antimicrobial activity against Gram(+Ve), i.e. Staphylococcus aureus, Bacillus subtilis, and Gram(-Ve), i.e. Serratia marcescens, Pseudomonas aeruginosa and Escherichia coli, microorganisms in terms of minimum inhibitory concentration and colony-forming unit. To determine the binding mode of complexes with Herring Sperm DNA, absorption titration and viscosity measurement were employed. DNA cleavage activity was carried out by gel electrophoresis experiment using supercoiled form of pUC19 DNA. The complexes were tested for their superoxide dismutase mimic activity in terms of IC(50) value. Synthesized complexes were also screened for their cytotoxicity using brine shrimp lethality assay method. PMID:23306896

  19. Exploring the DNA binding mode of transition metal based biologically active compounds

    NASA Astrophysics Data System (ADS)

    Raman, N.; Sobha, S.

    2012-01-01

    Few novel 4-aminoantipyrine derived Schiff bases and their metal complexes were synthesized and characterized. Their structural features and other properties were deduced from the elemental analysis, magnetic susceptibility and molar conductivity as well as from mass, IR, UV-vis, 1H NMR and EPR spectral studies. The binding of the complexes with CT-DNA was analyzed by electronic absorption spectroscopy, viscosity measurement, and cyclic voltammetry. The interaction of the metal complexes with DNA was also studied by molecular modeling with special reference to docking. The experimental and docking results revealed that the complexes have the ability of interaction with DNA of minor groove binding mode. The intrinsic binding constants ( Kb) of the complexes with CT-DNA were found out which show that they are minor groove binders. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pUC19 DNA in the presence of AH 2 (ascorbic acid). Moreover, the oxidative cleavage studies using distamycin revealed the minor groove binding for the newly synthesized 4-aminoantipyrine derived Schiff bases and their metal complexes. Evaluation of antibacterial activity of the complexes against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and Klebsiella pneumoniae exhibited that the complexes have potent biocidal activity than the free ligands.

  20. Biology and clinical relevance of granulysin

    PubMed Central

    Krensky, A. M.; Clayberger, C.

    2009-01-01

    Granulysin is a cytolytic and proinflammatory molecule first identified by a screen for genes expressed ‘late’ (3–5 days) after activation of human peripheral blood mononuclear cells. Granulysin is present in cytolytic granules of cytotoxic T lymphocytes and natural killer cells. Granulysin is made in a 15-kDa form that is cleaved into a 9-kDa form at both the amino and the carboxy termini. The 15-kDa form is constitutively secreted, and its function remains poorly understood. The 9-kDa form is released by receptor-mediated granule exocytosis. Nine kiloDalton granulysin is broadly cytolytic against tumors and microbes, including gram-positive and gram-negative bacteria, fungi/yeast and parasites. It kills the causative agents of both tuberculosis and malaria. Granulysin is also a chemoattractant for T lymphocytes, monocytes and other inflammatory cells and activates the expression of a number of cytokines, including regulated upon activation T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1α, interleukin (IL)-10, IL-1, IL-6 and interferon (IFN)-α. Granulysin is implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies. Small synthetic forms of granulysin are being developed as novel antibiotics. Studies of the full-length forms may give rise to new diagnostics and therapeutics for use in a wide variety of diseases. PMID:19254247

  1. Sirtuin biology and relevance to diabetes treatment

    PubMed Central

    Dong, X Charlie

    2012-01-01

    SUMMARY Sirtuins are a group of NAD+-dependent enzymes that post-translationally modify histones and other proteins. Among seven mammalian sirtuins, SIRT1 has been the most extensively studied and has been demonstrated to play a critical role in all major metabolic organs and tissues. SIRT1 regulates glucose and lipid homeostasis in the liver, modulates insulin secretion in pancreatic islets, controls insulin sensitivity and glucose uptake in skeletal muscle, increases adiponectin expression in white adipose tissue and controls food intake and energy expenditure in the brain. Recently, SIRT3 has been demonstrated to modulate insulin sensitivity in skeletal muscle and systemic metabolism, and Sirt3-null mice manifest characteristics of metabolic syndrome on a high-fat diet. Thus, it is reasonable to believe that enhancing the activities of SIRT1 and SIRT3 may be beneficial for Type 2 diabetes. Although it is controversial, the SIRT1 activator SRT1720 has been reported to be effective in improving glucose metabolism and insulin sensitivity in animal models. More research needs to be conducted so that we can better understand the physiological functions and molecular mechanisms of sirtuins in order to therapeutically target these enzymes for diabetes treatment. PMID:23024708

  2. Mammalian Sirtuins: Biological Insights and Disease Relevance

    PubMed Central

    Haigis, Marcia C.; Sinclair, David A.

    2010-01-01

    Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years. PMID:20078221

  3. Nitric oxide. Novel biology with clinical relevance.

    PubMed Central

    Billiar, T R

    1995-01-01

    OBJECTIVE: The author provides the reader with a view of the regulation and function of nitric oxide (NO), based on the three distinct enzyme isoforms that synthesize NO. SUMMARY BACKGROUND DATA: Nitric oxide is a short-lived molecule exhibiting functions as diverse as neurotransmission and microbial killing. Recent advances in the characterization of the enzymes responsible for NO synthesis and in the understanding of how NO interacts with targets have led to new insights into the many facets of this diverse molecule. METHODS: Nitric oxide is produced by one of three enzyme isoforms of NO synthesis. These enzymes vary considerably in their distribution, regulation, and function. Accordingly, the NO synthesis or lack of NO production will have consequences unique to that isoform. Therefore, this review summarizes the regulation and function of NO generated by each of the three isoforms. RESULTS: Nitric oxide exhibits many unique characteristics that allow this molecule to perform so many functions. The amount, duration, and location of the NO synthesis will depend on the isoform of NO synthase expressed. For each isoform, there probably are disease processes in which deficiency states exist. For induced NO synthesis, states of overexpression exist. CONCLUSIONS: Understanding the regulation and function of the enzymes that produce NO and the unique characteristics of each enzyme isoform is likely to lead to therapeutic approaches to prevent or treat a number of diseases. PMID:7537035

  4. Prion biology relevant to bovine spongiform encephalopathy.

    PubMed

    Novakofski, J; Brewer, M S; Mateus-Pinilla, N; Killefer, J; McCusker, R H

    2005-06-01

    Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE literature is characterized by subsequently unsupported claims of species barriers or absolute tissue safety. This review presents an overview of TSE and summarizes recent research on pathogenesis and transmission. PMID:15890824

  5. Formability Evaluation of Sheet Metals Based on Global Strain Distribution

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Lin, Jianping; Min, Junying; Ye, You; Kang, Liugen

    2016-04-01

    According to the conventional methods for formability evaluation, e.g., forming limit curve (FLC), limit dome height, and total elongation, inconsistent results are observed when comparing the formability of four advanced high-strength steels (AHSS) with an ultimate tensile strength grade of 1000 MPa. The strain distribution analysis with the aid of digital image correlation technique shows that different uniform deformation capabilities of sheet metals under the same loading conditions are responsible for this inconsistency. In addition, metallurgical analysis suggests that inhomogeneous microstructure distribution and phase transformation during deformation in some materials play important roles in the uniform deformation capability of sheet metal. Limit strains on the commonly used FLC only relate to the major and minor strains of local deforming elements associated with the onset of necking. However, the formability of a sheet metal component is determined by the strain magnitudes of all deforming elements involved during the forming process. Hence, the formability evaluation of sheet metals from a global aspect is more applicable for practical engineering. A new method based on two indices (i.e., which represent global formability and uniform deformation capability, respectively) is proposed to evaluate the formability of sheet metals based on global strain distribution. The formability and evolution of deformation uniformity of the investigated AHSS at different stress states are studied with this new method. Compared with other formability evaluation methods, the new method is demonstrated to be more appropriate for practical engineering, and it is applicable to both in-plane and out-of-plane deformation. Additionally, the global formability of sheet metals can be more comprehensively understood with this new method.

  6. Formability Evaluation of Sheet Metals Based on Global Strain Distribution

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Lin, Jianping; Min, Junying; Ye, You; Kang, Liugen

    2016-06-01

    According to the conventional methods for formability evaluation, e.g., forming limit curve (FLC), limit dome height, and total elongation, inconsistent results are observed when comparing the formability of four advanced high-strength steels (AHSS) with an ultimate tensile strength grade of 1000 MPa. The strain distribution analysis with the aid of digital image correlation technique shows that different uniform deformation capabilities of sheet metals under the same loading conditions are responsible for this inconsistency. In addition, metallurgical analysis suggests that inhomogeneous microstructure distribution and phase transformation during deformation in some materials play important roles in the uniform deformation capability of sheet metal. Limit strains on the commonly used FLC only relate to the major and minor strains of local deforming elements associated with the onset of necking. However, the formability of a sheet metal component is determined by the strain magnitudes of all deforming elements involved during the forming process. Hence, the formability evaluation of sheet metals from a global aspect is more applicable for practical engineering. A new method based on two indices (i.e., which represent global formability and uniform deformation capability, respectively) is proposed to evaluate the formability of sheet metals based on global strain distribution. The formability and evolution of deformation uniformity of the investigated AHSS at different stress states are studied with this new method. Compared with other formability evaluation methods, the new method is demonstrated to be more appropriate for practical engineering, and it is applicable to both in-plane and out-of-plane deformation. Additionally, the global formability of sheet metals can be more comprehensively understood with this new method.

  7. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

    PubMed Central

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P

    2015-01-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

  8. Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs.

    PubMed

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P; Esteves, Pedro J

    2015-11-01

    ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

  9. The X-ray Crystal Structure of the Phage Tail Terminator Protein Reveals the Biologically Relevant Hexameric Rang Structure and Demonstrates a Conserved mechanism of Tail Termination among Divrse Long Tailed Phages

    SciTech Connect

    Pell, L.; Liu, A; Edmonds, L; Donaldson, L; Howell, L; Davidson, A

    2009-01-01

    The tail terminator protein (TrP) plays an essential role in phage tail assembly by capping the rapidly polymerizing tail once it has reached its requisite length and serving as the interaction surface for phage heads. Here, we present the 2.7-A crystal structure of a hexameric ring of gpU, the TrP of phage ?. Using sequence alignment analysis and site-directed mutagenesis, we have shown that this multimeric structure is biologically relevant and we have delineated its functional surfaces. Comparison of the hexameric crystal structure with the solution structure of gpU that we previously solved using NMR spectroscopy shows large structural changes occurring upon multimerization and suggests a mechanism that allows gpU to remain monomeric at high concentrations on its own, yet polymerize readily upon contact with an assembled tail tube. The gpU hexamer displays several flexible loops that play key roles in head and tail binding, implying a role for disorder-to-order transitions in controlling assembly as has been observed with other ? morphogenetic proteins. Finally, we have found that the hexameric structure of gpU is very similar to the structure of a putative TrP from a contractile phage tail even though it displays no detectable sequence similarity. This finding coupled with further bioinformatic investigations has led us to conclude that the TrPs of non-contractile-tailed phages, such as ?, are evolutionarily related to those of contractile-tailed phages, such as P2 and Mu, and that all long-tailed phages may utilize a conserved mechanism for tail termination.

  10. Photodynamic Therapy and the Development of Metal-Based Photosensitisers

    PubMed Central

    Josefsen, Leanne B.; Boyle, Ross W.

    2008-01-01

    Photodynamic therapy (PDT) is a treatment modality that has been used in the successful treatment of a number of diseases and disorders, including age-related macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a combination of a selectively localised light-sensitive drug (known as a photosensitiser) and light of an appropriate wavelength. The light-activated form of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS) and radicals; in a biological environment these toxic species can interact with cellular constituents causing biochemical disruption to the cell. If the homeostasis of the cell is altered significantly then the cell enters the process of cell death. The first photosensitiser to gain regulatory approval for clinical PDT was Photofrin. Unfortunately, Photofrin has a number of associated disadvantages, particularly pro-longed patient photosensitivity. To try and overcome these disadvantages second and third generation photosensitisers have been developed and investigated. This Review highlights the key photosensitisers investigated, with particular attention paid to the metallated and non-metallated cyclic tetrapyrrolic derivatives that have been studied in vitro and in vivo; those which have entered clinical trials; and those that are currently in use in the clinic for PDT. PMID:18815617

  11. Earthdata Search: The Relevance of Relevance

    NASA Technical Reports Server (NTRS)

    Quinn, Patrick

    2016-01-01

    Through recent usability studies, the issue of relevance became increasingly clear in the Earthdata Search Client. After all, if a user can't find the data they are looking for, nothing else we do matters. This presentation walks through usability testing findings and recent relevance improvements made to the Earthdata Search Client.

  12. Ballistic Hot Electron Transport in Heteroepitaxial SrRuO3 Metal-Base Transistors

    NASA Astrophysics Data System (ADS)

    Kim, Brian; Hikita, Yasuyuki; Yajima, Takeaki; Bell, Christopher; Hwang, Harold

    Perovskite oxide heterostructures is a rapidly emerging field significant for interface-induced electronic and magnetic reconstructions, resulting in novel phases distinct from those found in the bulk counterparts. Notably, utilizing device structures is an effective way to probe these interface-induced phases. One of the most prevalent device structures that has been adopted so far is a three-terminal field-effect geometry, used to probe in-plane electronic transport properties. However, the out-of-plane three-terminal device geometry, though less studied due to its complexity, is also useful in many aspects. In the metal-base transistor (MBT), for instance, ballistic transport of hot electrons injected across a Schottky diode emitter can be used to probe hot electron properties of the metal-base, providing information on inelastic scattering mechanisms, electron confinement effects, and intervalley transfer. One promising model system for the metal-base is SrRuO3 (SRO), characterized by intermediate electron correlations with unusual transport properties. Here we present an all-perovskite oxide heteroepitaxial MBT using SRO as a metal-base layer. Successful MBT operation for various metal-base layer thicknesses was achieved, from which the hot electron attenuation length of SRO was deduced. These results form a foundation on which to examine the properties of hot electrons in strongly correlated systems using the out-of-plane three-terminal device geometry.

  13. Bivalent metal-based MIL-53 analogues: Synthesis, properties and application

    SciTech Connect

    Liu, Yongxin; Liu, Dan; Wang, Cheng

    2015-03-15

    Trivalent metal-based MIL-53 (Al{sup 3+}, Cr{sup 3+}, Fe{sup 3+}, In{sup 3+}) compounds are interesting metal–organic frameworks (MOFs) with breathing effect and are promising gas sorption materials. Replacing bridging μ{sub 2}-OH group by neutral ligands such as pyridine N-oxide and its derivatives (PNOs), the trivalent metal-based MIL-53 analogous structures could be extended to bivalent metal systems. The introduction of PNOs and bivalent metal elements endows the frameworks with new structural features and physical and chemical properties. This minireview summarizes the recent development of bivalent metal-based MIL-53 analogues (Mn{sup 2+}, Co{sup 2+}, Ni{sup 2+}), typically, focusing on the synthetic strategies and potential applications based on our own works and literatures. We present the synthetic strategy to achieve structures evolution from single-ligand-walled to double-ligand-walled channel. Properties and application of these new materials in a wide range of potential areas are discussed including thermal stability, gas adsorption, magnetism and liquid-phase separation. Promising directions of this research field are also highlighted. - Graphical abstract: The recent development of bivalent metal-based MIL-53 analogues (Mn{sup 2+}, Co{sup 2+}, Ni{sup 2+}) on their synthetic strategies, properties and potential applications was reviewed. - Highlights: • Structure features of bivalent metal-based MIL-53 analogues are illustrated. • Important properties and application are presented. • Host–guest interactions are main impetus for liquid-phase separation. • Promising directions of bivalent metal-based MIL-53 analogues are highlighted.

  14. Synthesis and property investigation of metal-based nanomaterials for biotechnological applications

    NASA Astrophysics Data System (ADS)

    Darsanasiri, Nalin Dammika

    Luminescent lanthanide-based materials have drawn recent interest due to their applications in in vitro cellular imaging. Sensitive biological analysis requires optical labels with high water dispersibility & stability and excellent luminescent properties. Most literature reported lanthanide complexes with high luminescence intensity are hydrophobic and unstable, limiting their biological applications. This project was designed to incorporate a highly luminescent lanthanide beta-diketonate complex in a silica nanoparticle. Eu(btfa)3dmph complex was synthesized, which exhibits red luminescence at 614 nm with a narrow (15 nm) full with half-maximum (btfa=4,4,4-trifluoro-1-phenyl-1,3-butanedione, dmph=4,7-dimethyl,1,10-phenanthroline). A synthetic procedure was optimized to incorporate the Eu-complex in a silica-based nanoparticle with an average particle diameter of 36 nm. Eu-complex based silica nanoparticles exhibit high stability and water-dispersibility with a luminescence quantum yield of 10 %. The nanoparticles showed antimicrobial activity against clinically important E.coli, S.aureus and S.epidermidis. Synthesis, materials characterization, and antimicrobial studies of the complex and the nanoparticles was discussed in the first part of this thesis. Nanotechnology is emerging as a new interdisciplinary field combining biology, chemistry, physics, and material science. Recent advances promise developments in the synthesis, modification and practical applications of polymer-coated manganese (Mn)-based zinc oxide (ZnO) nanoparticles (NPs). The size distribution, shape, and surface modification of metal-based ZnO nanoparticles are the key factors determining their specific physical properties. Due to the strong antibacterial properties and low toxicity towards mammalian cells, ZnO NPs have been successfully used in a wide range of applications including wound dressing, protective clothing, antibacterial surfaces, food preservation, and cosmetics as biocidal and

  15. Engineered metal based nanomaterials in aqueous environments: Interactions, transformations and implications

    NASA Astrophysics Data System (ADS)

    Mudunkotuwa, Imali Ama

    Nanoscience and nanotechnology offer potential routes towards addressing critical issues such as clean and sustainable energy, environmental protection and human health. Specifically, metal and metal oxide nanomaterials are found in a wide range of applications and therefore hold a greater potential of possible release into the environment or for the human to be exposed. Understanding the aqueous phase behavior of metal and metal oxide nanomaterials is a key factor in the safe design of these materials because their interactions with living systems are always mediated through the aqueous phase. Broadly the transformations in the aqueous phase can be classified as dissolution, aggregation and adsorption which are dependent and linked processes to one another. The complexity of these processes at the liquid-solid interface has therefore been one of the grand challenges that has persisted since the beginning of nanotechnology. Although classical models provide guidance for understanding dissolution and aggregation of nanoparticles in water, there are many uncertainties associated with the recent findings. This is often due to a lack of fundamental knowledge of the surface structure and surface energetics for very small particles. Therefore currently the environmental health and safety studies related to nanomaterials are more focused on understanding the surface chemistry that governs the overall processes in the liquid-solid interfacial region at the molecular level. The metal based nanomaterials focused on in this dissertation include TiO2, ZnO, Cu and CuO. These are among the most heavily used in a number of applications ranging from uses in the construction industry to cosmetic formulation. Therefore they are produced in large scale and have been detected in the environment. There is debate within the scientific community related to their safety as a result of the lack of understanding on the surface interactions that arise from the detailed nature of the surfaces

  16. Single Particle ICPMS for Characterizing Metal-based Nanoparticles and Monitoring Transformation Processes in Surface Water

    EPA Science Inventory

    Engineered metal-based nanomaterials will likely be used in increasing quantities in consumer and industrial products. These may be introduced into surface waters by a variety of paths depending on usage. Other naturally occurring and anthropogenic particles containing these met...

  17. Characterizing Metal-Based Nanoparticles in Surface Water by Single-Particle ICPMS

    EPA Science Inventory

    Engineered metal-based nanomaterials are being used in increasing quantities in consumer and industrial products. These materials may be introduced into surface waters by a variety of paths depending on usage, and will be superimposed on concentrations of other particles containi...

  18. SINGLE-PARTICLE ICPMS FOR CHARACTERIZING METAL-BASED NANOPARTICLES IN THE ENVIRONMENT - ADVANCES AND CHALLENGES

    EPA Science Inventory

    As engineered metal-based nanomaterials become widely used in consumer and industrial products, the amount of these materials introduced into the environment by a variety of paths will increase. The concentration of metal associated with these engineered nanoparticles will be s...

  19. The Importance of Being Relevant

    PubMed Central

    Jaswal, Snehlata

    2012-01-01

    This review aims at an understanding of the binding process by synthesizing the extant perspectives regarding binding. It begins with a consideration of the biological explanations of binding, viz., conjunctive coding, synchrony, and reentrant mechanisms. Thereafter binding is reviewed as a psychological process guided by top-down signals. The stages and types of binding proposed by various researchers are discussed in this section. The next section introduces Working Memory (WM) as the executive directing the top-down signals. After that it is described how WM works by selecting relevant sensory input, followed by a detailed consideration of the debate regarding objects vs. features with the conclusion that relevance is the key factor determining what is processed. The next section considers other factors affecting the selection of relevant input. Then, we shift focus to describe what happens to irrelevant input – whether it is discarded at the outset or is gradually inhibited, and whether inhibition is a perceptual or post-perceptual process. The concluding section describes the process of binding as currently understood on the basis of the literature included in the review. To summarize, it appears that initially the “object” is conceptualized as an instantaneous bundle of all features. However, only relevant features of stimuli are gradually integrated to form a stable representation of the object. Concomitantly, irrelevant features are removed from the object representations. Empirical evidence suggests that the inhibition of irrelevant features occurs over time and is presumably a process within WM. PMID:22969739

  20. Perceptions of document relevance

    PubMed Central

    Bruza, Peter; Chang, Vivien

    2014-01-01

    This article presents a study of how humans perceive and judge the relevance of documents. Humans are adept at making reasonably robust and quick decisions about what information is relevant to them, despite the ever increasing complexity and volume of their surrounding information environment. The literature on document relevance has identified various dimensions of relevance (e.g., topicality, novelty, etc.), however little is understood about how these dimensions may interact. We performed a crowdsourced study of how human subjects judge two relevance dimensions in relation to document snippets retrieved from an internet search engine. The order of the judgment was controlled. For those judgments exhibiting an order effect, a q–test was performed to determine whether the order effects can be explained by a quantum decision model based on incompatible decision perspectives. Some evidence of incompatibility was found which suggests incompatible decision perspectives is appropriate for explaining interacting dimensions of relevance in such instances. PMID:25071622

  1. Rigor, Relevance and Relationships

    ERIC Educational Resources Information Center

    McNulty, Raymond J.; Quaglia, Russell J.

    2007-01-01

    Rigor, relevance, and relationships are three elements that provide the hallmark for education today. These three elements are integrally connected; if one is missing in a teacher's teaching practices, he or she is not doing his or her best to prepare students for success in school and in life. To ensure the inclusion of both rigor and relevance,…

  2. Making Science Relevant

    ERIC Educational Resources Information Center

    Eick, Charles; Deutsch, Bill; Fuller, Jennifer; Scott, Fletcher

    2008-01-01

    Science teachers are always looking for ways to demonstrate the relevance of science to students. By connecting science learning to important societal issues, teachers can motivate students to both enjoy and engage in relevant science (Bennet, Lubben, and Hogarth 2007). To develop that connection, teachers can help students take an active role in…

  3. Culturally Relevant Pedagogy

    ERIC Educational Resources Information Center

    Irvine, Jacqueline Jordan

    2010-01-01

    Many teachers have only a cursory understanding of culturally relevant pedagogy, and their efforts to bridge the cultural gap often fall short. Culturally relevant pedagogy is a term that describes effective teaching in culturally diverse classrooms. It can be a daunting idea to understand and implement. Yet people tend to appreciate culturally…

  4. Removal of inorganic mercury and methylmercury from surface waters following coagulation of dissolved organic matter with metal-based salts

    USGS Publications Warehouse

    Henneberry, Y.K.; Kraus, T.E.C.; Fleck, J.A.; Krabbenhoft, D.P.; Bachand, P.M.; Horwath, W.R.

    2011-01-01

    The presence of inorganic mercury (IHg) and methylmercury (MeHg) in surface waters is a health concern worldwide. This study assessed the removal potential use of metal-based coagulants as a means to remove both dissolved IHg and MeHg from natural waters and provides information regarding the importance of Hg associations with the dissolved organic matter (DOM) fraction and metal hydroxides. Previous research indicated coagulants were not effective at removing Hg from solution; however these studies used high concentrations of Hg and did not reflect naturally occurring concentrations of Hg. In this study, water collected from an agricultural drain in the Sacramento-San Joaquin Delta was filtered to isolate the dissolved organic matter (DOM) fraction. The DOM was then treated with a range of coagulant doses to determine the efficacy of removing all forms of Hg from solution. Three industrial-grade coagulants were tested: ferric chloride, ferric sulfate, and polyaluminum chloride. Coagulation removed up to 85% of DOM from solution. In the absence of DOM, all three coagulants released IHg into solution, however in the presence of DOM the coagulants removed up to 97% of IHg and 80% of MeHg. Results suggest that the removal of Hg is mediated by DOM-coagulant interactions. There was a preferential association of IHg with the more aromatic, higher molecular weight fraction of DOM but no such relationship was found for MeHg. This study offers new fundamental insights regarding large-scale removal of Hg at environmentally relevant regarding large-scale removal of Hg at environmentally relevant concentrations.

  5. Defining a metal-based waste form for IFR pyroprocessing wastes

    SciTech Connect

    McDeavitt, S.M.; Park, J.Y.; Ackerman, J.P.

    1994-01-01

    Pyrochemical electrorefining to recover actinides from metal nuclear fuel is a key element of the Integral Fast Reactor (IFR) fuel cycle. The process separates the radioactive fission products from the long-lived actinides in a molten LiCl-KCl salt, and it generates a lower waste volume with significantly less long-term toxicity as compared to spent nuclear fuel. The process waste forms include a mineral-based waste form that will contain fission products removed from an electrolyte salt and a metal-based waste form that will contain metallic fission products and the fuel cladding and process materials. Two concepts for the metal-based waste form are being investigated: (1) encapsulating the metal constituents in a Cu-Al alloy and (2) alloying the metal constituents into a uniform stainless steel-based waste form. Results are given from our recent studies of these two concepts.

  6. Partial-surface-passivation strategy for transition-metal-based copper-gold nanocage.

    PubMed

    Liu, Shoujie; Zheng, Xusheng; Song, Li; Liu, Wei; Yao, Tao; Sun, Zhihu; Lin, Yue; Wei, Shiqiang

    2016-05-01

    An effective strategy involving the corrosion of partial-surface-passivated Cu nanoparticles is proposed for synthesizing transition-metal-based Cu-Au alloy nanocages. Time-dependent X-ray absorption spectroscopy demonstrates that the hollow-cage Cu-Au alloy nanostructure is formed by sequential erosion of the partial surface and interior Cu and by the alloying of Au and Cu. PMID:27116561

  7. Sverdrup's Biology

    NASA Astrophysics Data System (ADS)

    McGowan, J.

    2002-12-01

    Sverdrup's contribution to Biological Oceanography were more than merely substantial, they were of fundamental importance. His plan for the training of graduate students at Scripps did not recognize the traditional division of the basic disciplines into separate categories of physics, chemistry, biology and geology. He insisted that Oceanography was a multi-disciplinary subject and that all entering students should study all four subjects. Today this is not very unusual but it was in the early 50s when I took those courses. We biologists carried away from those courses an appreciation of the importance of both spatial and temporal scale. It was of clear relevance to problems of oceanic population and community biology. But there was still more to his biology. He is responsible for a very simple, but very elegant model of the regulation of oceanic primary productivity. The elements of this model are found today in the ten or so highly derivative models. He also published a map predicting global ocean productivity based on the ideas in the model plus some wonderfully intuitive thinking. This map does not differ strongly from those glorious false color ones being published today.

  8. Bioinformatics and School Biology

    ERIC Educational Resources Information Center

    Dalpech, Roger

    2006-01-01

    The rapidly changing field of bioinformatics is fuelling the need for suitably trained personnel with skills in relevant biological "sub-disciplines" such as proteomics, transcriptomics and metabolomics, etc. But because of the complexity--and sheer weight of data--associated with these new areas of biology, many school teachers feel…

  9. Bivalent metal-based MIL-53 analogues: Synthesis, properties and application

    NASA Astrophysics Data System (ADS)

    Liu, Yongxin; Liu, Dan; Wang, Cheng

    2015-03-01

    Trivalent metal-based MIL-53 (Al3+, Cr3+, Fe3+, In3+) compounds are interesting metal-organic frameworks (MOFs) with breathing effect and are promising gas sorption materials. Replacing bridging μ2-OH group by neutral ligands such as pyridine N-oxide and its derivatives (PNOs), the trivalent metal-based MIL-53 analogous structures could be extended to bivalent metal systems. The introduction of PNOs and bivalent metal elements endows the frameworks with new structural features and physical and chemical properties. This minireview summarizes the recent development of bivalent metal-based MIL-53 analogues (Mn2+, Co2+, Ni2+), typically, focusing on the synthetic strategies and potential applications based on our own works and literatures. We present the synthetic strategy to achieve structures evolution from single-ligand-walled to double-ligand-walled channel. Properties and application of these new materials in a wide range of potential areas are discussed including thermal stability, gas adsorption, magnetism and liquid-phase separation. Promising directions of this research field are also highlighted.

  10. Load-bearing capacity and biological allowable limit of biodegradable metal based on degradation rate in vivo.

    PubMed

    Cho, Sung Youn; Chae, Soo-Won; Choi, Kui Won; Seok, Hyun Kwang; Han, Hyung Seop; Yang, Seok Jo; Kim, Young Yul; Kim, Jong Tac; Jung, Jae Young; Assad, Michel

    2012-08-01

    In this study, a newly developed Mg-Ca-Zn alloy for low degradation rate and surface erosion properties was evaluated. The compressive, tensile, and fatigue strength were measured before implantation. The degradation behavior was evaluated by analyzing the microstructure and local hardness of the explanted specimen. Mean and maximum degradation rates were measured using micro CT equipment from 4-, 8-, and 16- week explants, and the alloy was shown to display surface erosion properties. Based on these characteristics, the average and minimum load bearing capacities in tension, compression, and bending modes were calculated. According to the degradation rate and references of recommended dietary intakes (RDI), the Mg-Ca-Zn alloy appears to be safe for human use. PMID:22689439

  11. Ceramics reinforced metal base composite coatings produced by CO II laser cladding

    NASA Astrophysics Data System (ADS)

    Yang, Xichen; Wang, Yu; Yang, Nan

    2008-03-01

    Due to the excellent performance in high strength, anti-temperature and anti-wear, ceramics reinforced metal base composite material was used in some important fields of aircraft, aerospace, automobile and defense. The traditional bulk metal base composite materials are the expensive cost, which is limited in its industrial application. Development of laser coating of ceramics reinforced metal base composite is very interesting in economy. This paper is focused on three laser cladding ceramics coatings of SiC particle /Al matrix , Al IIO 3 powder/ Al matrix and WC + Co/mild steel matrix. Powder particle sizes are of 10-60μm. Chemical contents of aluminum matrix are of 3.8-4.0% Cu, 1.2-1.8% Mg, 0.3-0.99% Mn and balance Al. 5KW CO II laser, 5 axes CNC table, JKF-6 type powder feeder and co-axis feeder nozzle are used in laser cladding. Microstructure and performance of laser composite coatings have been respectively examined with OM,SEM and X-ray diffraction. Its results are as follows : Microstructures of 3C-,6H- and 5H- SiC particles + Al + Al 4SiC 4 + Si in SiC/Al composite, hexagonal α-Al IIO 3 + cubic γ-Al IIO 3 + f.c.c Al in Al IIO 3 powder/ Al composite and original WC particles + separated WC particles + eutectic WC + γ-Co solid solution + W IIC particles in WC + Co/steel coatings are respectively recognized. New microstructures of 5H-SiC in SiC/Al composite, cubic γ-Al IIO 3 in Al IIO 3 composite and W IIC in WC + Co/ steel composite by laser cladding have been respectively observed.

  12. Relevance, Derogation and Permission

    NASA Astrophysics Data System (ADS)

    Stolpe, Audun

    We show that a recently developed theory of positive permission based on the notion of derogation is hampered by a triviality result that indicates a problem with the underlying full-meet contraction operation. We suggest a solution that presupposes a particular normal form for codes of norms, adapted from the theory of relevance through propositional letter sharing. We then establish a correspondence between contractions on sets of norms in input/output logic (derogations), and AGM-style contractions on sets of formulae, and use it as a bridge to migrate results on propositional relevance from the latter to the former idiom. Changing the concept accordingly we show that positive permission now incorporates a relevance requirement that wards off triviality.

  13. Integrated Design and Rapid Development of Refractory Metal Based Alloys for Fossil Energy Applications

    SciTech Connect

    Dogan, O.N.; King, P.E.; Gao, M.C.

    2008-07-01

    One common barrier in the development of new technologies for future energy generating systems is insufficiency of existing materials at high temperatures (>1150oC) and aggressive atmospheres (e.g., steam, oxygen, CO2). To overcome this barrier, integrated design methodology will be applied to the development of refractory metal based alloys. The integrated design utilizes the multi-scale computational methods to design materials for requirements of processing and performance. This report summarizes the integrated design approach to the alloy development and project accomplishments in FY 2008.

  14. High-energy in-beam neutron measurements of metal-based shielding for accelerator-driven spallation neutron sources

    NASA Astrophysics Data System (ADS)

    DiJulio, D. D.; Cooper-Jensen, C. P.; Björgvinsdóttir, H.; Kokai, Z.; Bentley, P. M.

    2016-05-01

    Metal-based shielding plays an important role in the attenuation of harmful and unwanted radiation at an accelerator-driven spallation neutron source. At the European Spallation Source, currently under construction in Lund, Sweden, metal-based materials are planned to be used extensively as neutron guide substrates in addition to other shielding structures around neutron guides. The usage of metal-based materials in the vicinity of neutron guides however requires careful consideration in order to minimize potential background effects in a neutron instrument at the facility. Therefore, we have carried out a combined study involving high-energy neutron measurements and Monte Carlo simulations of metal-based shielding, both to validate the simulation methodology and also to investigate the benefits and drawbacks of different metal-based solutions. The measurements were carried out at The Svedberg Laboratory in Uppsala, Sweden, using a 174.1 MeV neutron beam and various thicknesses of aluminum-, iron-, and copper-based shielding blocks. The results were compared to geant4 simulations and revealed excellent agreement. Our combined study highlights the particular situations where one type of metal-based solution may be preferred over another.

  15. Implementation and performance evaluation of a database of chemical formulas for the screening of pharmaco/toxicologically relevant compounds in biological samples using electrospray ionization-time-of-flight mass spectrometry.

    PubMed

    Polettini, Aldo; Gottardo, Rossella; Pascali, Jennifer Paola; Tagliaro, Franco

    2008-04-15

    Electrospray ionization (ESI)-time-of-flight (TOF) MS enables searching a wide number of pharmaco/toxicologically relevant compounds (PTRC) in biosamples. However, the number of identifiable PTRC depends on extension of reference database of chemical formulas/compound names. Previous approaches proposed in-house or commercial databases with limitations either in PTRC number or content (e.g., few metabolites, presence of non-PTRC). In the frame of development of a ESI-TOF PTRC screening procedure, a subset of PubChem Compound as reference database is proposed. Features of this database (approximately 50,500 compounds) are illustrated, and its performance evaluated through analysis by capillary electrophoresis (CE)-ESI-TOF of hair/blood/urine collected from subjects under treatment with known drugs or by comparison with reference standards. The database is rich in parent compounds of pharmaceutical and illicit drugs, pesticides, and poisons and contains many metabolites (including about 6000 phase I metabolites and 180 glucuronides) and related substances (e.g., impurities, esters). The average number of hits with identical chemical formula is 1.82 +/- 2.27 (median = 1, range 1-39). Minor deficiencies, redundancies, and errors have been detected that do not limit the potential of the database in identifying unknown PTRC. The database allows a much broader search for PTRC than other commercial/in-house databases of chemical formulas/compound names previously proposed. However, the probability that a search retrieves different PTRC having identical chemical formula is higher than with smaller databases, and additional information (anamnestic/circumstantial data, concomitant presence of parent drug and metabolite, selective sample preparation, liquid chromatographic retention, and CE migration behavior) must be used in order to focus the search more tightly. PMID:18336013

  16. Core Bioactive Components Promoting Blood Circulation in the Traditional Chinese Medicine Compound Xueshuantong Capsule (CXC) Based on the Relevance Analysis between Chemical HPLC Fingerprint and In Vivo Biological Effects

    PubMed Central

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei

    2014-01-01

    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  17. Blending Rigor and Relevance

    ERIC Educational Resources Information Center

    Siri, Diane K.; Zinner, Jane; Lezin, Nicole

    2011-01-01

    A collaborative at several sites across the state of California will offer evidence of how successful linked learning, which connects academics to real-world work, can be. This article presents examples that illustrate the powerful connections and linkages that are generated by combining academic rigor with the relevance of applying learning to…

  18. Is Information Still Relevant?

    ERIC Educational Resources Information Center

    Ma, Lia

    2013-01-01

    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  19. The Relevance of Literature.

    ERIC Educational Resources Information Center

    Dunham, L. L.

    1971-01-01

    The "legacy" of the humanities is discussed in terms of relevance, involvement, and other philosophical considerations. Reasons for studying foreign literature in language classes are developed in the article. Comment is also made on attitudes and ideas culled from the writings of Clifton Fadiman, Jean Paul Sartre, and James Baldwin. (RL)

  20. Reading, Writing and Relevance.

    ERIC Educational Resources Information Center

    Hoffman, Mary

    This monograph presents classroom activities that were designed to encourage children to read and write in a self-reliant and responsible manner. The activities were chosen for their relevance to the children involved and because the vocabulary involved was interesting, familiar, and worth remembering and using again. The topics are arranged in…

  1. One-pot green synthesis of biologically relevant novel spiro[indolin-2-one-3,4'-pyrano[2,3-c]pyrazoles] and studies on their spectral and X-ray crystallographic behaviors.

    PubMed

    Sharma, Sakshi; Brahmachari, Goutam; Kant, Rajni; Gupta, Vivek K

    2016-06-01

    Syntheses via green route and single-crystal X-ray structural investigations have been carried out for three spiro[indolin-2-one-3,4'-pyrano[2,3-c]pyrazole] derivatives, 6'-amino-2-oxo-3'-propyl-2'H-spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile dimethyl sulfoxide monosolvate (5a), 6'-amino-5-fluoro-2-oxo-3'-propyl-2'H-spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile dimethyl sulfoxide monosolvate (5b) and methyl 6'-amino-5-cyano-1-methyl-2-oxo-3'-propyl-2'H-spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-3'-carboxylate 0.25 hydrate (5c), respectively. Compounds (5a) and (5b) crystallize in the triclinic space group P\\bar 1, whereas compound (5c) crystallizes in the monoclinic space group C2/c. In molecules (5a) and (5b) all the rings are practically flat, while in (5c), the heterocyclic pyran ring adopts a flattened-boat conformation. In (5a) and (5b) the cyanide group is oriented in a (-ap) conformation, while the amino group is oriented in a (+ap) conformation with a pyran ring, but in (5c) both the cyanide and amino groups are oriented in a (-ap) conformation with the pyran ring. In the crystal structure of (5a) and (5b), the molecules are linked by an elaborate system of N-H...O and N-H...N hydrogen bonds to generate a zigzag-like construct. In (5c) molecules are linked by N-H...O hydrogen bonds, thereby generating extended chains. The present communication focuses on the detailed and comparative information about spectral behaviors, single-crystal X-ray crystallographic properties and solid-state supramolecular architectures of these synthesized compounds of potential biological interests. PMID:27240765

  2. Theoretical investigation of all-metal-based mushroom plasmonic metamaterial absorbers at infrared wavelengths

    NASA Astrophysics Data System (ADS)

    Ogawa, Shinpei; Fujisawa, Daisuke; Kimata, Masafumi

    2015-12-01

    High-performance wavelength-selective infrared (IR) sensors require small pixel structures, a low-thermal mass, and operation in the middle-wavelength infrared (MWIR) and long-wavelength infrared (LWIR) regions for multicolor IR imaging. All-metal-based mushroom plasmonic metamaterial absorbers (MPMAs) were investigated theoretically and were designed to enhance the performance of wavelength-selective uncooled IR sensors. All components of the MPMAs are based on thin layers of metals such as Au without oxide insulators for increased absorption. The absorption properties of the MPMAs were investigated by rigorous coupled-wave analysis. Strong wavelength-selective absorption is realized over a wide range of MWIR and LWIR wavelengths by the plasmonic resonance of the micropatch and the narrow-gap resonance, without disturbance from the intrinsic absorption of oxide insulators. The absorption wavelength is defined mainly by the micropatch size and is longer than its period. The metal post width has less impact on the absorption properties and can maintain single-mode operation. Through-holes can be formed on the plate area to reduce the thermal mass. A small pixel size with reduced thermal mass and wideband single-mode operation can be realized using all-metal-based MPMAs.

  3. Investigating extent of dissolved organic carbon stabilization by metal based coagulant in a wetland environment

    NASA Astrophysics Data System (ADS)

    Henneberry, Y.; Mourad, D.; Kraus, T.; Bachand, P.; Fujii, R.; Horwath, W.

    2008-12-01

    This study is part of a larger project designed to investigate the feasibility of using metal-based coagulants to remove dissolved organic carbon (DOC) from island drainage water in the San Joaquin Delta and subsequently retaining the metal-DOC precipitate (floc) in wetlands constructed at the foot of levees to promote levee stability. Dissolved organic carbon is a constituent of concern as some forms of DOC can be converted to carcinogenic compounds during drinking water treatment. The focus of this work is to assess floc stability over time and to determine whether floc can be permanently sequestered as part of wetland sediment. Drainage water collected seasonally from Twitchell Island was coagulated with ferric sulfate and polyaluminum chloride at optimal and 50%-optimal dosage levels. Floc was incubated in the laboratory under anaerobic conditions for six weeks under various conditions including different DOC concentrations, microbial inoculants, and addition of nutrients. Preliminary results indicate the floc is a stable system; little to no DOC was released from the floc into the water column under incubations with native microbial inoculate. In addition, floc incubated with previously coagulated water appeared to remove additional DOC from the water column. Future work will involve field and laboratory studies using 13C labeled plant material to examine the effects of fresh plant matter and the effects of peat soil DOC on floc stability, in order to elucidate mechanisms behind carbon stabilization by metal-based floc.

  4. Noble metal based plasmonic nanomaterials and their application for bio-imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Zhu, Dewei

    During the past two decades, researchers have gained more and more insight into the manipulation of nanomaterials to create useful technologies. Numerous classes of nanomaterials have been produced and studied based upon their intriguing chemical and physical properties and their potential applications in diverse fields, ranging from electronics to renewable energy and biomedicine. In this dissertation, we describe the synthesis and potential biomedical applications of several types of noble metal-based nanomaterials in which we control size, shape, and coupling to other materials to tune their localized surface plasmon resonance (LSPR) interaction with light. We demonstrate the application of these novel nanostructures as contrast agents for photoacoustic imaging and as photosensitizers for photothermal therapy. Chapter one first presents protocols for producing monodisperse spherical nanoparticles of gold and silver. The diameter of the nanospheres can be adjusted from less than 2 nm to greater than 10 nm by controlling the reaction conditions, including ligands that cap the nanosphere surfaces, reaction time, and reaction temperature. Next, we describe the synthesis of multi-branched Au nanocrystals with predominantly tripodal, tetrapodal and star-shaped morphologies. We demonstrate tuning of the LSPR energy in these materials by changing the branch length. In the third part of this chapter, we present a novel method for coupling heavily-doped p-type copper selenide (Cu2-xSe) NPs with Au NPs by seeded nanocrystal growth to form a new type of semiconductor-metal heterogeneous nanostructure. This new class of plasmonic nanomaterials can simultaneously exhibit two types of LSPR in a single system, producing a broad optical absorbance that is nearly flat across the near infrared (NIR) spectral region (750-1150nm), along with a small shoulder at 566 nm that originates from the Au NP. We conclude this first chapter by demonstrating the use of self-doped copper sulfide

  5. Noble metal based plasmonic nanomaterials and their application for bio-imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Zhu, Dewei

    During the past two decades, researchers have gained more and more insight into the manipulation of nanomaterials to create useful technologies. Numerous classes of nanomaterials have been produced and studied based upon their intriguing chemical and physical properties and their potential applications in diverse fields, ranging from electronics to renewable energy and biomedicine. In this dissertation, we describe the synthesis and potential biomedical applications of several types of noble metal-based nanomaterials in which we control size, shape, and coupling to other materials to tune their localized surface plasmon resonance (LSPR) interaction with light. We demonstrate the application of these novel nanostructures as contrast agents for photoacoustic imaging and as photosensitizers for photothermal therapy. Chapter one first presents protocols for producing monodisperse spherical nanoparticles of gold and silver. The diameter of the nanospheres can be adjusted from less than 2 nm to greater than 10 nm by controlling the reaction conditions, including ligands that cap the nanosphere surfaces, reaction time, and reaction temperature. Next, we describe the synthesis of multi-branched Au nanocrystals with predominantly tripodal, tetrapodal and star-shaped morphologies. We demonstrate tuning of the LSPR energy in these materials by changing the branch length. In the third part of this chapter, we present a novel method for coupling heavily-doped p-type copper selenide (Cu2-xSe) NPs with Au NPs by seeded nanocrystal growth to form a new type of semiconductor-metal heterogeneous nanostructure. This new class of plasmonic nanomaterials can simultaneously exhibit two types of LSPR in a single system, producing a broad optical absorbance that is nearly flat across the near infrared (NIR) spectral region (750-1150nm), along with a small shoulder at 566 nm that originates from the Au NP. We conclude this first chapter by demonstrating the use of self-doped copper sulfide

  6. Biological Threats

    MedlinePlus

    ... Thunderstorms & Lightning Tornadoes Tsunamis Volcanoes Wildfires Main Content Biological Threats Biological agents are organisms or toxins that ... Centers for Disease Control and Prevention . Before a Biological Threat Unlike an explosion, a biological attack may ...

  7. Experimental technique for studying high-temperature phase equilibria in reactive molten metal based systems

    NASA Astrophysics Data System (ADS)

    Ermoline, Alexandre

    The general objective of this work is to develop an experimental technique for studying the high-temperature phase compositions and phase equilibria in molten metal-based binary and ternary systems, such as Zr-O-N, B-N-O, Al-O, and others. A specific material system of Zr-O-N was selected for studying and testing this technique. The information about the high-temperature phase equilibria in reactive metal-based systems is scarce and their studying is difficult because of chemical reactions occurring between samples and essentially any container materials, and causing contamination of the system. Containerless microgravity experiments for studying equilibria in molten metal-gas systems were designed to be conducted onboard of a NASA KC-135 aircraft flying parabolic trajectories. A uniaxial apparatus suitable for acoustic levitation, laser heating, and splat quenching of small samples was developed and equipped with computer-based controller and optical diagnostics. Normal-gravity tests were conducted to determine the most suitable operating parameters of the levitator by direct observations of the levitated samples, as opposed to more traditional pressure mapping of the acoustic field. The size range of samples that could be reliably heated and quenched in this setup was determined to be on the order of 1--3 mm. In microgravity experiments, small spherical specimens (1--2 mm diameter), prepared as pressed, premixed solid components, ZrO2, ZrN, and Zr powders, were acoustically levitated inside an argon-filled chamber at one atmosphere and heated by a CO2 laser. The levitating samples could be continuously laser heated for about 1 sec, resulting in local sample melting. The sample stability in the vertical direction was undisturbed by simultaneous laser heating. Oscillations of the levitating sample in the horizontal direction increased while it was heated, which eventually resulted in the movement of the sample away from its stable levitation position and the laser

  8. Computational Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2013-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007). The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology / systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology. PMID:20838980

  9. Quasiparticle band structure of the almost-gapless transition-metal-based Heusler semiconductors

    NASA Astrophysics Data System (ADS)

    Tas, M.; Şaşıoǧlu, E.; Galanakis, I.; Friedrich, C.; Blügel, S.

    2016-05-01

    Transition-metal-based Heusler semiconductors are promising materials for a variety of applications ranging from spintronics to thermoelectricity. Employing the G W approximation within the framework of the FLAPW method, we study the quasiparticle band structure of a number of such compounds being almost gapless semiconductors. We find that in contrast to the s p -electron based semiconductors such as Si and GaAs, in these systems, the many-body corrections have a minimal effect on the electronic band structure and the energy band gap increases by less than 0.2 eV, which makes the starting point density functional theory (DFT) a good approximation for the description of electronic and optical properties of these materials. Furthermore, the band gap can be tuned either by the variation of the lattice parameter or by the substitution of the s p -chemical element.

  10. Insights on Metal Based Dental Implants and their Interaction with the Surrounding Tissues.

    PubMed

    Popa, Marcela; Hussien, Mohamed D; Cirstea, Alexandra; Grigore, Raluca; Lazar, Veronica; Bezirtzoglou, Eugenia; Chifiriuc, Mariana Carmen; Sakizlian, Monica; Stavropoulou, Elisavet; Bertesteanu, Serban

    2015-01-01

    At present, the use of dental implants is a very common practice as tooth loss is a frequent problem and can occur as a result of disease or trauma. An implant is usually made of biocompatible materials that do not cause rejection reactions and allow the implant union with the respective bone. To achieve this goal, the implant surface may have different structures and coatings, generally used to increase the adherence of the implant to the bone and to decrease the risk of the periimplantar inflammatory reactions. This review gives some insights of the metal based materials used for dental implants, their limits, improvement strategies as well as the pathophysiology, diagnosis, treatment and prevention of periimplantary diseases. PMID:25877088

  11. Metal-dielectric-metal based narrow band absorber for sensing applications.

    PubMed

    Lu, Xiaoyuan; Wan, Rengang; Zhang, Tongyi

    2015-11-16

    We have investigated numerically the narrowband absorption property of a metal-dielectric-metal based structure which includes a top metallic nanoring arrays, a metal backed plate, and a middle dielectric spacer. Its absorption is up to 90% with linewidth narrower than 10 nm. This can be explained in terms of surface lattice resonance of the periodic structure. The spectrum with the sharp absorption dip, i.e. the lattice resonance, strongly depends on the refractive index of media surrounding the nanorings. This feature can be explored to devise a refractive index sensor, of which the bulk sensitivity factor is one order larger than that based on gap resonance mode, while the surface sensitivity factor can be two times larger. The proposed narrowband absorber has potential in applications of plasmonic biosensors. PMID:26698467

  12. Morally relevant potential.

    PubMed

    Hershenov, David B; Hershenov, Rose J

    2015-03-01

    Fetuses and infants are said to warrant protecting because of their potential. But valuing potential supposedly leads to absurdities like protecting cells that could be technologically altered to develop into persons. This can be avoided by recognising that morally relevant potential is determined by what is presently healthy development (proper functioning) for an organism. The only interests of mindless organisms are in the flourishing that necessarily depends upon their healthy functioning. They can be harmed when those interests are frustrated. We criticise McMahan for claiming that harm is instead a function of the degree of psychological ties to the future. PMID:24570396

  13. Information Theory in Biology after 18 Years

    ERIC Educational Resources Information Center

    Johnson, Horton A.

    1970-01-01

    Reviews applications of information theory to biology, concluding that they have not proved very useful. Suggests modifications and extensions to increase the biological relevance of the theory, and speculates about applications in quantifying cell proliferation, chemical homeostasis and aging. (EB)

  14. Vygotsky's Crisis: Argument, context, relevance.

    PubMed

    Hyman, Ludmila

    2012-06-01

    Vygotsky's The Historical Significance of the Crisis in Psychology (1926-1927) is an important text in the history and philosophy of psychology that has only become available to scholars in 1982 in Russian, and in 1997 in English. The goal of this paper is to introduce Vygotsky's conception of psychology to a wider audience. I argue that Vygotsky's argument about the "crisis" in psychology and its resolution can be fully understood only in the context of his social and political thinking. Vygotsky shared the enthusiasm, widespread among Russian leftist intelligentsia in the 1920s, that Soviet society had launched an unprecedented social experiment: The socialist revolution opened the way for establishing social conditions that would let the individual flourish. For Vygotsky, this meant that "a new man" of the future would become "the first and only species in biology that would create itself." He envisioned psychology as a science that would serve this humanist teleology. I propose that The Crisis is relevant today insofar as it helps us define a fundamental problem: How can we systematically account for the development of knowledge in psychology? I evaluate how Vygotsky addresses this problem as a historian of the crisis. PMID:22520196

  15. Relevant Features of Science: Values in Conservation Biology

    ERIC Educational Resources Information Center

    van Dijk, Esther M.

    2013-01-01

    The development of an understanding of the nature of science is generally assumed to be an important aspect of science communication with respect to the enhancement of scientific literacy. At present, a general characterization of the nature of science is still lacking and probably such a characterization will not be achievable. The overall aim of…

  16. Towards a barrier height benchmark set for biologically relevant systems

    PubMed Central

    Kromann, Jimmy C.; Christensen, Anders S.; Cui, Qiang

    2016-01-01

    We have collected computed barrier heights and reaction energies (and associated model structures) for five enzymes from studies published by Himo and co-workers. Using this data, obtained at the B3LYP/6- 311+G(2d,2p)[LANL2DZ]//B3LYP/6-31G(d,p) level of theory, we then benchmark PM6, PM7, PM7-TS, and DFTB3 and discuss the influence of system size, bulk solvation, and geometry re-optimization on the error. The mean absolute differences (MADs) observed for these five enzyme model systems are similar to those observed for PM6 and PM7 for smaller systems (10–15 kcal/mol), while DFTB results in a MAD that is significantly lower (6 kcal/mol). The MADs for PMx and DFTB3 are each dominated by large errors for a single system and if the system is disregarded the MADs fall to 4–5 kcal/mol. Overall, results for the condensed phase are neither more or less accurate relative to B3LYP than those in the gas phase. With the exception of PM7-TS, the MAD for small and large structural models are very similar, with a maximum deviation of 3 kcal/mol for PM6. Geometry optimization with PM6 shows that for one system this method predicts a different mechanism compared to B3LYP/6-31G(d,p). For the remaining systems, geometry optimization of the large structural model increases the MAD relative to single points, by 2.5 and 1.8 kcal/mol for barriers and reaction energies. For the small structural model, the corresponding MADs decrease by 0.4 and 1.2 kcal/mol, respectively. However, despite these small changes, significant changes in the structures are observed for some systems, such as proton transfer and hydrogen bonding rearrangements. The paper represents the first step in the process of creating a benchmark set of barriers computed for systems that are relatively large and representative of enzymatic reactions, a considerable challenge for any one research group but possible through a concerted effort by the community. We end by outlining steps needed to expand and improve the data set and how other researchers can contribute to the process. PMID:27168993

  17. Towards a barrier height benchmark set for biologically relevant systems.

    PubMed

    Kromann, Jimmy C; Christensen, Anders S; Cui, Qiang; Jensen, Jan H

    2016-01-01

    We have collected computed barrier heights and reaction energies (and associated model structures) for five enzymes from studies published by Himo and co-workers. Using this data, obtained at the B3LYP/6- 311+G(2d,2p)[LANL2DZ]//B3LYP/6-31G(d,p) level of theory, we then benchmark PM6, PM7, PM7-TS, and DFTB3 and discuss the influence of system size, bulk solvation, and geometry re-optimization on the error. The mean absolute differences (MADs) observed for these five enzyme model systems are similar to those observed for PM6 and PM7 for smaller systems (10-15 kcal/mol), while DFTB results in a MAD that is significantly lower (6 kcal/mol). The MADs for PMx and DFTB3 are each dominated by large errors for a single system and if the system is disregarded the MADs fall to 4-5 kcal/mol. Overall, results for the condensed phase are neither more or less accurate relative to B3LYP than those in the gas phase. With the exception of PM7-TS, the MAD for small and large structural models are very similar, with a maximum deviation of 3 kcal/mol for PM6. Geometry optimization with PM6 shows that for one system this method predicts a different mechanism compared to B3LYP/6-31G(d,p). For the remaining systems, geometry optimization of the large structural model increases the MAD relative to single points, by 2.5 and 1.8 kcal/mol for barriers and reaction energies. For the small structural model, the corresponding MADs decrease by 0.4 and 1.2 kcal/mol, respectively. However, despite these small changes, significant changes in the structures are observed for some systems, such as proton transfer and hydrogen bonding rearrangements. The paper represents the first step in the process of creating a benchmark set of barriers computed for systems that are relatively large and representative of enzymatic reactions, a considerable challenge for any one research group but possible through a concerted effort by the community. We end by outlining steps needed to expand and improve the data set and how other researchers can contribute to the process. PMID:27168993

  18. Annexin A2: biology and relevance to the antiphospholipid syndrome

    PubMed Central

    Cockrell, E; Espinola, RG; McCrae, KR

    2012-01-01

    Antiphospholipid antibodies (aPL), the majority of which are directed against β2-glycoprotein I (β2GPI), are associated with an increased incidence of venous and arterial thrombosis. The pathogenesis of antiphospholipid/anti-β2GPI-associated thrombosis has not been defined, and is likely multifactorial. However, accumulating evidence suggests an important role for endothelial cell activation with the acquisition of a procoagulant phenotype by the activated endothelial cell. Previous work demonstrated that endothelial activation by antiphospholipid/anti-β2GPI antibodies is β2GPI-dependent. We extended these observations by defining annexin A2 as an endothelial β2GPI binding site. We also observed that annexin A2 plays a critical role in endothelial cell activation induced by anti-β2GPI antibodies, and others have described direct endothelial activation by anti-annexin A2 antibodies in patients with aPL. Similar findings have been reported using human monocytes, which also express annexin A2. Because annexin A2 is not a transmembrane protein, how binding of β2GPI/anti-β2GPI antibodies, or anti-annexin A2 antibodies, to endothelial annexin A2 causes cellular activation is unknown. Recent studies, however, suggest an important role for the Toll-like receptor family, particularly TLR4. In this article, we review the role of these interactions in the activation of endothelial cells by aPL. The influence of these antibodies on the ability of annexin A2 to enhance t-PA-mediated plasminogen activation is also discussed. PMID:18827060

  19. Physical and Biological Interactions of Intact Watersheds: Are they relevant?

    NASA Astrophysics Data System (ADS)

    Bryant, M.

    2005-05-01

    Intact watersheds are rare or absent throughout most of the northern hemisphere. Southeast Alaska is an exception with many forested watersheds that either have not been or are lightly disturbed by human activity. The Kadashan River, a short (less than 20 km) river in an old growth watershed on Chichagof Island is one example of an intact watershed. Natural processes from the headwaters to the ocean interact to create a salmon rich environment. Steep headwater streams are sources for sediment recruitment, nutrients (organic material and invertebrates), and large wood. Large riparian trees entering the stream provide long term storage of sediment, create pools, and link the main stream to off-channel habitats. A natural discharge regime that floods a complex riparian zone with abundant beaver ponds is a key process that maintains this complex system. Examples of these processes and salmonid populations in the Kadashan River illustrate how they interact to support one of the more productive watersheds in southeast Alaska. Understanding and quantifying processes in intact watersheds provide an opportunity to test major river paradigms and provide reference points for watershed restoration projects elsewhere.

  20. The Importance of Biologically Relevant Microclimates in Habitat Suitability Assessments

    PubMed Central

    Varner, Johanna; Dearing, M. Denise

    2014-01-01

    Predicting habitat suitability under climate change is vital to conserving biodiversity. However, current species distribution models rely on coarse scale climate data, whereas fine scale microclimate data may be necessary to assess habitat suitability and generate predictive models. Here, we evaluate disparities between temperature data at the coarse scale from weather stations versus fine-scale data measured in microhabitats required for a climate-sensitive mammal, the American pika (Ochotona princeps). We collected two years of temperature data in occupied talus habitats predicted to be suitable (high elevation) and unsuitable (low elevation) by the bioclimatic envelope approach. At low elevations, talus surface and interstitial microclimates drastically differed from ambient temperatures measured on-site and at a nearby weather station. Interstitial talus temperatures were frequently decoupled from high ambient temperatures, resulting in instantaneous disparities of over 30°C between these two measurements. Microhabitat temperatures were also highly heterogeneous, such that temperature measurements within the same patch of talus were not more correlated than measurements at distant patches. An experimental manipulation revealed that vegetation cover may cool the talus surface by up to 10°C during the summer, which may contribute to this spatial heterogeneity. Finally, low elevation microclimates were milder and less variable than typical alpine habitat, suggesting that, counter to species distribution model predictions, these seemingly unsuitable habitats may actually be better refugia for this species under climate change. These results highlight the importance of fine-scale microhabitat data in habitat assessments and underscore the notion that some critical refugia may be counterintuitive. PMID:25115894

  1. Synthesis of glycophostones: cyclic phosphonate analogues of biologically relevant sugars

    PubMed

    Hanessian; Rogel

    2000-05-01

    Analogues of L-fucose, N-acetyl-D-glucosamine, N-acetyl-D-mannosamine, and N-acetyl neuraminic acid in which the anomeric carbon atom was replaced by a phosphonyl group (phostones or cyclic phosphonates) were synthesized by stereocontrolled methods relying on the Abramov reaction. PMID:10808439

  2. Cooperativity in noncovalent interactions of biologically relevant molecules.

    PubMed

    Antony, Jens; Brüske, Björn; Grimme, Stefan

    2009-10-14

    Using a recently published benchmark MP2 database of nucleic acid base trimers, the three-body contribution to the interaction energy (TBE, also termed (non)cooperativity) as a function of base composition and complex geometry is studied. In 28 out of 141 cases (or 20%), the counterpoise-corrected MP2/TZV(2df,2pd) TBE exceeds 1 kcal mol(-1). The TBE is below 1 kcal mol(-1) for all trimers in the benchmark set consisting of U, T, and A, irrespective of the geometrical arrangement in the database. The largest MP2/TZV(2df,2pd) cooperativity of -9 kcal mol(-1) is obtained for a hydrogen-bonded guanine trimer. The largest anti-cooperativity occurs for a protonated cytosine-guanine-cytosine trimer (6 kcal mol(-1)). Generally, the many-body non-additivity term is an order of magnitude smaller than the interaction energies (on average -33 kcal mol(-1)). Employing various density functionals (GGA, meta-GGA, and hybrid) and wave function methods up to third order perturbation theory, and using atomic-orbital basis sets of double-, triple-, and quadruple-zeta quality, we find that the non-additivity effects are almost independent of one particle basis set and method. To enable an interpretation of the TBE, the intermolecular interaction energy is subjected to an energy decomposition analysis (EDA) with a similar definition of the energy terms as the Morokuma decomposition scheme. We find that nonadditive effects are mainly due to the induction, while exchange repulsion, electrostatic, and dispersion contributions are essentially additive, the latter also beyond second order at the MP3/SV(d,p) level. The performance of dispersion-corrected density functional theory for the prediction of structures and binding energies is assessed. While an accurate reproduction of the MP2-optimized reference structures of the trimers can already be accomplished with modern density functionals, only the inclusion of the long-range (London) dispersion interaction provides a consistent picture for both structures and binding energies. PMID:19774274

  3. Biologically Relevant Exposure Science for 21st Century Toxicity Testing

    EPA Science Inventory

    High visibility efforts in toxicity testing and computational toxicology including the recent NRC report, Toxicity Testing in the 21st Century: a Vision and Strategy (NRC, 2007), raise important research questions and opportunities for the field of exposure science. The authors ...

  4. Evaluation of Colloidal Stability and Ecotoxicity of Metal-based Nanoparticles in the Aquatic and Terrestrial Systems

    NASA Astrophysics Data System (ADS)

    Pokhrel, Lok Raj

    NPs, ZnONPs, or their ions. Overall, various metal-based nanoparticles revealed lower toxicity than their ions against multiple organisms. This study showed that particle size, surface properties, and ion release kinetics of AgNPs modify following release into aquatic environment, suggesting potential implications to ecosystem health and functions, and that caution be applied when extending one species toxicity results to another because obvious differences in organism biology---supporting species sensitivity paradigm---can significantly alter nanoparticle or ionic toxicity.

  5. Discovery of a 3d-transition-metal-based ferromagnetic Kondo lattice system

    NASA Astrophysics Data System (ADS)

    Us Saleheen, Ahmad; Samanta, Tapas; Lepkowski, Daniel; Shankar, Alok; Prestigiacomo, Joseph; Dubenko, Igor; Quetz, Abdiel; McDougald, Roy, Jr.; McCandless, Gregory; Chan, Julia; Adams, Philip; Young, David; Ali, Naushad; Stadler, Shane

    2015-03-01

    The formation of a Kondo lattice results in a wide variety of exotic phenomena associated with the competition between the Kondo effect and the RKKY interaction, such as heavy fermions, non-Fermi liquid behavior, unconventional superconductivity, and so on. A quantum critical point (QCP) has been frequently observed at the boundaries of competing phases for antiferromagnetic materials. However, the existence of a ferromagnetic (FM) QCP is unclear. Moreover, FM Kondo lattices are rare. Here we report the discovery of a FM Kondo lattice system Mn1-xFexCoGe, which is the first example of a 3d-metal-based system (i.e., not rare-earth-based). Resistivity, magnetic susceptibility, heat capacity and thermopower studies on a single crystal sample indicate that the anisotropic FM kondo lattice has formed along c-axis. The signature of a spin density wave transition was also observed above the Kondo minimum, below which the resistivity follows a log(T) behavior. This work was supported by the U.S. Department of Energy (Grant Nos. DE-FG02-13ER46946 and DE-FG02-06ER46291).

  6. Simulation of the emission properties of patterned metal-based nanostructures

    NASA Astrophysics Data System (ADS)

    Li, Weijun; Luo, Jun; Peng, Sha; Zhu, Yaping; Lei, Yu; Tong, Qing; Zhang, Xinyu; Sang, Hongshi; Xie, Changsheng

    2015-12-01

    Enormous pressures have been puts on current optical storage technologies as the rapid development of information technologies. Recently, it has been found that the surface plasmon-polaritons'modes (SPPMs) in metallic nanostructures may lead to the high localization of guided light beams with nanometer size and only limited by several factors such as atomic structure, dissipation, and light dispersion, and thus far beyond the common diffraction limit of electromagnetic waves in dielectric media. This discovery provides a way to produce nanoscale light signal and thus makes a significant breakthrough in optical storage technologies. In this paper, our work focuses on the modeling and simulation of particular kinds of patterned metal-based nanostructure fabricated over silicon dioxide (SiO2) wafer. The nanostructures designed are expected to concentrate, deliver incident light energy into nanoscale regions and generate nanoscale light signal. In our research, the duty cycle of patterned nanostructures is taken as a key parameter, and then the factors including the patterned nanostructures, the frequency of the incident electromagnetic wave, the size of patterned nanostructure and the distance arrangement between adjacent single patterns, are taken as variables. The common CST microwave studio is used to simulate beam transportation and transformation behaviors. By comparing electric-field intensity distribution in nano-areas and the reflectance of the nanostructure array, the nano-light-emission effects are analyzed.

  7. Low-cost impact detection and location for automated inspections of 3D metallic based structures.

    PubMed

    Morón, Carlos; Portilla, Marina P; Somolinos, José A; Morales, Rafael

    2015-01-01

    This paper describes a new low-cost means to detect and locate mechanical impacts (collisions) on a 3D metal-based structure. We employ the simple and reasonably hypothesis that the use of a homogeneous material will allow certain details of the impact to be automatically determined by measuring the time delays of acoustic wave propagation throughout the 3D structure. The location of strategic piezoelectric sensors on the structure and an electronic-computerized system has allowed us to determine the instant and position at which the impact is produced. The proposed automatic system allows us to fully integrate impact point detection and the task of inspecting the point or zone at which this impact occurs. What is more, the proposed method can be easily integrated into a robot-based inspection system capable of moving over 3D metallic structures, thus avoiding (or minimizing) the need for direct human intervention. Experimental results are provided to show the effectiveness of the proposed approach. PMID:26029951

  8. Characterizing and modeling electrical response to light for metal-based EUV photoresists

    NASA Astrophysics Data System (ADS)

    Pret, Alessandro V.; Kocsis, Mike; De Simone, Danilo; Vandenberghe, Geert; Stowers, Jason; Giglia, Angelo; de Schepper, Peter; Mani, Antonio; Biafore, John J.

    2016-03-01

    Metal-based photoresists are appealing for use in EUV lithography due to their improved etch resistance and absorption compared with organic resists, and due to their resolving power demonstrated with 13.53 nm exposures using synchrotron light. Recently imec has started a new project to study novel photoresists for EUV lithography, with particular attention to metal containing materials, in order to explore alternative approaches that may offer superior characteristics in photoresist imaging and etching performance compared with more mature chemically amplified resists. In order to model these novel resists it is mandatory to understand both the optical properties and the electronic response to photon absorption. As in previous experiments on organic materials, some of the optical properties can be determined by merging analysis from high-energy electron scattering models (e.g. CXRO website), X-ray absorption spectroscopy, and DUV spectroscopic ellipsometry. Dispersion curves can be used to calculate the electronic inelastic and elastic mean-free paths; convolved with the expected spectrum at wafer level it is possible to estimate the electron yield and the secondary electron blur of the photoresist. These material properties can be used to modify the physical models currently used to simulate organic photoresist performance in computational lithography software.

  9. Low-Cost Impact Detection and Location for Automated Inspections of 3D Metallic Based Structures

    PubMed Central

    Morón, Carlos; Portilla, Marina P.; Somolinos, José A.; Morales, Rafael

    2015-01-01

    This paper describes a new low-cost means to detect and locate mechanical impacts (collisions) on a 3D metal-based structure. We employ the simple and reasonably hypothesis that the use of a homogeneous material will allow certain details of the impact to be automatically determined by measuring the time delays of acoustic wave propagation throughout the 3D structure. The location of strategic piezoelectric sensors on the structure and an electronic-computerized system has allowed us to determine the instant and position at which the impact is produced. The proposed automatic system allows us to fully integrate impact point detection and the task of inspecting the point or zone at which this impact occurs. What is more, the proposed method can be easily integrated into a robot-based inspection system capable of moving over 3D metallic structures, thus avoiding (or minimizing) the need for direct human intervention. Experimental results are provided to show the effectiveness of the proposed approach. PMID:26029951

  10. Impact Ignition and Combustion Behavior of Amorphous Metal-Based Reactive Composites

    NASA Astrophysics Data System (ADS)

    Mason, Benjamin; Groven, Lori; Son, Steven

    2013-06-01

    Recently published molecular dynamic simulations have shown that metal-based reactive powder composites consisting of at least one amorphous component could lead to improved reaction performance due to amorphous materials having a zero heat of fusion, in addition to having high energy densities and potential uses such as structural energetic materials and enhanced blast materials. In order to investigate the feasibility of these systems, thermochemical equilibrium calculations were performed on various amorphous metal/metalloid based reactive systems with an emphasis on commercially available or easily manufactured amorphous metals, such as Zr and Ti based amorphous alloys in combination with carbon, boron, and aluminum. Based on the calculations and material availability material combinations were chosen. Initial materials were either mixed via a Resodyn mixer or mechanically activated using high energy ball milling where the microstructure of the milled material was characterized using x-ray diffraction, optical microscopy and scanning electron microscopy. The mechanical impact response and combustion behavior of select reactive systems was characterized using the Asay shear impact experiment where impact ignition thresholds, ignition delays, combustion velocities, and temperatures were quantified, and reported. Funding from the Defense Threat Reduction Agency (DTRA), Grant Number HDTRA1-10-1-0119. Counter-WMD basic research program, Dr. Suhithi M. Peiris, program director is gratefully acknowledged.

  11. Reproducible direct exposure environmental testing of metal-based magnetic media

    NASA Technical Reports Server (NTRS)

    Sides, Paul J.

    1994-01-01

    A flow geometry and flow rate for mixed flowing gas testing is proposed. Use of an impinging jet of humid polluted air can provide a uniform and reproducible exposure of coupons of metal-based magnetic media. Numerical analysis of the fluid flow and mass transfer in such as system has shown that samples confined within a distance equal to the nozzle radius on the surface of impingement are uniformly accessible to pollutants in the impinging gas phase. The critical factor is the nozzle height above the surface of impingement. In particular, the uniformity of exposure is less than plus/minus 2% for a volumetric flow rate of 1600 cm(exp 3)/minute total flow with the following specifications: For a one inch nozzle, the height of the nozzle opening above the stage should be 0.177 inches; for a 2 inch nozzle - 0.390 inches. Not only is the distribution uniform, but one can calculate the maximum delivery rate of pollutants to the samples for comparison with the observed deterioration.

  12. Biological Technicians

    MedlinePlus

    ... Biological technicians typically need a bachelor’s degree in biology or a closely related field. It is important ... Biological technicians typically need a bachelor’s degree in biology or a closely related field. It is important ...

  13. Ontologies for molecular biology.

    PubMed

    Schulze-Kremer, S

    1998-01-01

    Molecular biology has a communication problem. There are many databases using their own labels and categories for storing data objects and some using identical labels and categories but with a different meaning. A prominent example is the concept "gene" which is used with different semantics by major international genomic databases. Ontologies are one means to provide a semantic repository to systematically order relevant concepts in molecular biology and to bridge the different notions in various databases by explicitly specifying the meaning of and relation between the fundamental concepts in an application domain. Here, the upper level and a database branch of a prospective ontology for molecular biology (OMB) is presented and compared to other ontologies with respect to suitability for molecular biology (http:/(/)igd.rz-berlin.mpg.de/approximately www/oe/mbo.html). PMID:9697223

  14. Vibrations, quanta and biology

    NASA Astrophysics Data System (ADS)

    Huelga, S. F.; Plenio, M. B.

    2013-07-01

    Quantum biology is an emerging field of research that concerns itself with the experimental and theoretical exploration of non-trivial quantum phenomena in biological systems. In this tutorial overview we aim to bring out fundamental assumptions and questions in the field, identify basic design principles and develop a key underlying theme - the dynamics of quantum dynamical networks in the presence of an environment and the fruitful interplay that the two may enter. At the hand of three biological phenomena whose understanding is held to require quantum mechanical processes, namely excitation and charge transfer in photosynthetic complexes, magneto-reception in birds and the olfactory sense, we demonstrate that this underlying theme encompasses them all, thus suggesting its wider relevance as an archetypical framework for quantum biology.

  15. A brief survey of sensing for metal-based powder bed fusion additive manufacturing

    NASA Astrophysics Data System (ADS)

    Foster, Bryant K.; Reutzel, Edward W.; Nassar, Abdalla R.; Dickman, Corey J.; Hall, Benjamin T.

    2015-05-01

    Purpose - Powder bed fusion additive manufacturing (PBFAM) of metal components has attracted much attention, but the inability to quickly and easily ensure quality has limited its industrial use. Since the technology is currently being investigated for critical engineered components and is largely considered unsuitable for high volume production, traditional statistical quality control methods cannot be readily applied. An alternative strategy for quality control is to monitor the build in real time with a variety of sensing methods and, when possible, to correct any defects as they occur. This article reviews the cause of common defects in powder bed additive manufacturing, briefly surveys process monitoring strategies in the literature, and summarizes recently-developed strategies to monitor part quality during the build process. Design/methodology/approach - Factors that affect part quality in powder bed additive manufacturing are categorized as those influenced by machine variables and those affected by other build attributes. Within each category, multiple process monitoring methods are presented. Findings - A multitude of factors contribute to the overall quality of a part built using PBFAM. Rather than limiting processing to a pre-defined build recipe and assuming complete repeatability, part quality will be ensured by monitoring the process as it occurs and, when possible, altering the process conditions or build plan in real-time. Recent work shows promise in this area and brings us closer to the goal of wide-spread adoption of additive manufacturing technology. Originality/value - This work serves to introduce and define the possible sources of defects and errors in metal-based PBFAM, and surveys sensing and control methods which have recently been investigated to increase overall part quality. Emphasis has been placed on novel developments in the field and their contribution to the understanding of the additive manufacturing process.

  16. Bacteriophage lambda: early pioneer and still relevant

    PubMed Central

    Casjens, Sherwood R.; Hendrix, Roger W.

    2015-01-01

    Molecular genetic research on bacteriophage lambda carried out during its golden age from the mid 1950's to mid 1980's was critically important in the attainment of our current understanding of the sophisticated and complex mechanisms by which the expression of genes is controlled, of DNA virus assembly and of the molecular nature of lysogeny. The development of molecular cloning techniques, ironically instigated largely by phage lambda researchers, allowed many phage workers to switch their efforts to other biological systems. Nonetheless, since that time the ongoing study of lambda and its relatives have continued to give important new insights. In this review we give some relevant early history and describe recent developments in understanding the molecular biology of lambda's life cycle. PMID:25742714

  17. Bacteriophage lambda: Early pioneer and still relevant.

    PubMed

    Casjens, Sherwood R; Hendrix, Roger W

    2015-05-01

    Molecular genetic research on bacteriophage lambda carried out during its golden age from the mid-1950s to mid-1980s was critically important in the attainment of our current understanding of the sophisticated and complex mechanisms by which the expression of genes is controlled, of DNA virus assembly and of the molecular nature of lysogeny. The development of molecular cloning techniques, ironically instigated largely by phage lambda researchers, allowed many phage workers to switch their efforts to other biological systems. Nonetheless, since that time the ongoing study of lambda and its relatives has continued to give important new insights. In this review we give some relevant early history and describe recent developments in understanding the molecular biology of lambda's life cycle. PMID:25742714

  18. Chromosomal data relevant for Q values

    NASA Astrophysics Data System (ADS)

    Edwards, A. A.

    1992-07-01

    It has been known for many years that relationships between absorbed dose and biological effect vary with the type of radiation. In particular, neutrons and alpha particles are more damaging than x or γ radiations. This applies to a range of biological effects such as cell killing, chromosome aberrations, cell mutation, cell transformation as well as life shortening and cancer induction in animals. The application of this knowledge to devise a scheme for specifying the quality factor (Q) in radiological protection has been the subject of much debate. There are no tumour data in humans from which the quality factor may be derived. The problems of using animal and cell transformation data which are probably the next best choice are discussed. The extensive data base on chromosomal aberrations in human lymphocytes is described and discussed in terms of relevance to deducing quality factors. Particular emphasis is placed on data obtained at low doses and low dose rates.

  19. Relevance in the science classroom: A multidimensional analysis

    NASA Astrophysics Data System (ADS)

    Hartwell, Matthew F.

    While perceived relevance is considered a fundamental component of adaptive learning, the experience of relevance and its conceptual definition have not been well described. The mixed-methods research presented in this dissertation aimed to clarify the conceptual meaning of relevance by focusing on its phenomenological experience from the students' perspective. Following a critical literature review, I propose an identity-based model of perceived relevance that includes three components: a contextual target, an identity target, and a connection type, or lens. An empirical investigation of this model that consisted of two general phases was implemented in four 9th grade-biology classrooms. Participants in Phase 1 (N = 118) completed a series of four open-ended writing activities focused on eliciting perceived personal connections to academic content. Exploratory qualitative content analysis of a 25% random sample of the student responses was used to identify the main meaning-units of the proposed model as well as different dimensions of student relevance perceptions. These meaning-units and dimensions provided the basis for the construction of a conceptual mapping sentence capturing students' perceived relevance, which was then applied in a confirmatory analysis to all other student responses. Participants in Phase 2 (N = 139) completed a closed survey designed based on the mapping sentence to assess their perceived relevance of a biology unit. The survey also included scales assessing other domain-level motivational processes. Exploratory factor analysis and non-metric multidimensional scaling indicated a coherent conceptual structure, which included a primary interpretive relevance dimension. Comparison of the conceptual structure across various groups (randomly-split sample, gender, academic level, domain-general motivational profiles) provided support for its ubiquity and insight into variation in the experience of perceived relevance among students of different

  20. Biological and Chemical Security

    SciTech Connect

    Fitch, P J

    2002-12-19

    The LLNL Chemical & Biological National Security Program (CBNP) provides science, technology and integrated systems for chemical and biological security. Our approach is to develop and field advanced strategies that dramatically improve the nation's capabilities to prevent, prepare for, detect, and respond to terrorist use of chemical or biological weapons. Recent events show the importance of civilian defense against terrorism. The 1995 nerve gas attack in Tokyo's subway served to catalyze and focus the early LLNL program on civilian counter terrorism. In the same year, LLNL began CBNP using Laboratory-Directed R&D investments and a focus on biodetection. The Nunn-Lugar-Domenici Defense Against Weapons of Mass Destruction Act, passed in 1996, initiated a number of U.S. nonproliferation and counter-terrorism programs including the DOE (now NNSA) Chemical and Biological Nonproliferation Program (also known as CBNP). In 2002, the Department of Homeland Security was formed. The NNSA CBNP and many of the LLNL CBNP activities are being transferred as the new Department becomes operational. LLNL has a long history in national security including nonproliferation of weapons of mass destruction. In biology, LLNL had a key role in starting and implementing the Human Genome Project and, more recently, the Microbial Genome Program. LLNL has over 1,000 scientists and engineers with relevant expertise in biology, chemistry, decontamination, instrumentation, microtechnologies, atmospheric modeling, and field experimentation. Over 150 LLNL scientists and engineers work full time on chemical and biological national security projects.

  1. Biological Filters.

    ERIC Educational Resources Information Center

    Klemetson, S. L.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. The review is concerned with biological filters, and it covers: (1) trickling filters; (2) rotating biological contractors; and (3) miscellaneous reactors. A list of 14 references is also presented. (HM)

  2. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  3. Acrylic and metal based Y-branch plastic optical fiber splitter with optical NOA63 polymer waveguide taper region

    NASA Astrophysics Data System (ADS)

    Ehsan, Abang Annuar; Shaari, Sahbudin; Rahman, Mohd Kamil Abd.

    2011-01-01

    We proposed a simple low-cost acrylic and metal-based Y-branch plastic optical fiber (POF) splitter which utilizes a low cost optical polymer glue NOA63 as the main waveguiding medium at the waveguide taper region. The device is composed of three sections: an input POF waveguide, a middle waveguide taper region and output POF waveguides. A desktop high speed CNC engraver is utilized to produce the mold inserts used for the optical devices. Short POF fibers are inserted into the engraved slots at the input and output ports. UV curable optical polymer glue NOA63 is injected into the waveguide taper region and cured. The assembling is completed when the top plate is positioned to enclose the device structure and connecting screws are secured. Both POF splitters have an average insertion loss of 7.8 dB, coupling ratio of 55: 45 and 57: 43 for the acrylic and metal-based splitters respectively. The devices have excess loss of 4.82 and 4.73 dB for the acrylic and metal-based splitters respectively.

  4. On the Existence of Our Metals-Based Civilization: I. Phase Space Analysis

    SciTech Connect

    D.D. Macdonald

    2005-06-22

    than are equilibrium thermodynamic diagrams. Thus, KSDs more accurately account for the limits of passivity in highly acidic systems, where acid depassivation occurs, and at high potentials, where transition to the transpassive state may occur in some systems. In any event, phase space analysis of the PDM permits specification of the conditions over which reactive metals will remain passive in contact with aqueous systems and hence of the conditions that must be met for the existence of our metals-based civilization.

  5. Relevance of vitamin D in reproduction

    PubMed Central

    Luk, Janelle; Torrealday, Saioa; Neal Perry, Genevieve; Pal, Lubna

    2012-01-01

    The steroid hormone vitamin D is historically recognized for its relevance to bone health and calcium homeostasis. Recent years have witnessed a shift in focus to non-skeletal benefits of vitamin D; in this latter context, an accruing body of literature attests to a relevance of vitamin D to reproductive physiology. This article reviews the existing data about the diverse and previously underappreciated roles for vitamin D in reproductive health. A large body of available literature suggests that vitamin D deficiency may be detrimental to reproductive biology. However, given that our appreciation of vitamin D's role in reproductive physiology is almost entirely shaped by ‘associative’ studies and that data based on prospective interventional trials are limited, these concepts remain predominantly conjectural. Exact mechanisms whereby vitamin D may participate in the regulation of reproductive physiology remain far from clear. This review underscores a need for appropriately designed intervention trials to address the existing knowledge gaps and to delineate the specific roles of vitamin D signaling in reproductive biology. PMID:22824625

  6. [Biological markers of alcoholism].

    PubMed

    Marcos Martín, M; Pastor Encinas, I; Laso Guzmán, F J

    2005-09-01

    Diagnosis of alcoholism is very important, given its high prevalence and possibility of influencing the disease course. For this reason, the so-called biological markers of alcoholism are useful. These are analytic parameters that alter in the presence of excessive alcohol consumption. The two most relevant markers are the gamma-glutamyltranspeptidase and carbohydrate deficient transferrin. With this clinical comment, we aim to contribute to the knowledge of these tests and promote its use in the clinical practice. PMID:16194480

  7. [Biological weapons].

    PubMed

    Kerwat, K; Becker, S; Wulf, H; Densow, D

    2010-08-01

    Biological weapons are weapons of mass destruction that use pathogens (bacteria, viruses) or the toxins produced by them to target living organisms or to contaminate non-living substances. In the past, biological warfare has been repeatedly used. Anthrax, plague and smallpox are regarded as the most dangerous biological weapons by various institutions. Nowadays it seems quite unlikely that biological warfare will be employed in any military campaigns. However, the possibility remains that biological weapons may be used in acts of bioterrorism. In addition all diseases caused by biological weapons may also occur naturally or as a result of a laboratory accident. Risk assessment with regard to biological danger often proves to be difficult. In this context, an early identification of a potentially dangerous situation through experts is essential to limit the degree of damage. PMID:20717866

  8. Trends in Ground-State Entropies for Transition Metal Based Hydrogen Atom Transfer Reactions

    SciTech Connect

    Mader, Elizabeth A.; Manner, Virginia W.; Markle, Todd F.; Wu, Adam; Franz, James A.; Mayer, James M.

    2009-03-10

    Reported herein are thermochemical studies of hydrogen atom transfer (HAT) reactions involving transition metal H-atom donors MIILH and oxyl radicals. [FeII(H2bip)3]2+, [FeII(H2bim)3]2+, [CoII(H2bim)3]2+ and RuII(acac)2(py-imH) [H2bip = 2,2’-bi-1,4,5,6-tetrahydro¬pyrimidine, H2bim = 2,2’-bi-imidazoline, acac = 2,4-pentandionato, py-imH = 2-(2’-pyridyl)¬imidazole)] each react with TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) or tBu3PhO• (2,4,6-tri-tert-butylphenoxyl) to give the deprotonated, oxidized metal complex MIIIL, and TEMPOH or tBu3PhOH. Solution equilibrium measurements for the reactions of Co and Fe complexes with TEMPO show a large, negative ground-state entropy for hydrogen atom transfer: ΔSºHAT = -30 ± 2 cal mol-1 K-1 for the two iron complexes and -41 ± 2 cal mol-1 K-1 for [CoII(H2bim)3]2+. The ΔSºHAT for TEMPO + RuII(acac)2(py-imH) is much closer to zero, 4.9 ± 1.1 cal mol-1 K-1. Calorimetric measurements quantitatively confirm the enthalpy of reaction for [FeII(H2bip)3]2+ + TEMPO, thus also confirming ΔSºHAT. Calorimetry on TEMPOH + tBu3PhO• gives ΔHºHAT = 11.2 ± 0.5 kcal mol-1 which matches the enthalpy predicted from the difference in literature solution BDEs. An evaluation of the literature BDEs of both TEMPOH and tBu3PhOH is briefly presented and new estimates are included on the relative enthalpy of solvation for tBu3PhO• vs. tBu3PhOH. The primary contributor to the large magnitude of the ground-state entropy |ΔSºHAT| for the metal complexes is vibrational entropy, ΔSºvib. The common assumption that ΔSºHAT ≈ 0 for HAT reactions, developed for organic and small gas phase molecules, does not hold for transition metal based HAT reactions. The trend in magnitude of |ΔSºHAT| for reactions with TEMPO, RuII(acac)2(py-imH) << [FeII(H2bip)3]2+ = [FeII(H2bim)3]2+ < [CoII(H2bim)3]2+, is surprisingly well predicted by the trends for electron transfer half-reaction entropies, ΔSºET, in aprotic solvents. ΔSºET and

  9. Trends in Ground-State Entropies for Transition Metal Based Hydrogen Atom Transfer Reactions

    PubMed Central

    Mader, Elizabeth A.; Manner, Virginia W.; Markle, Todd F.; Wu, Adam; Franz, James A.; Mayer, James M.

    2009-01-01

    Reported herein are thermochemical studies of hydrogen atom transfer (HAT) reactions involving transition metal H-atom donors MIILH and oxyl radicals. [FeII(H2bip)3]2+, [FeII(H2bim)3]2+, [CoII(H2bim)3]2+ and RuII(acac)2(py-imH) [H2bip = 2,2’-bi-1,4,5,6-tetrahydropyrimidine, H2bim = 2,2’-bi-imidazoline, acac = 2,4-pentandionato, py-imH = 2-(2’-pyridyl)-imidazole)] each react with TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) or tBu3PhO• (2,4,6-tri-tert-butylphenoxyl) to give the deprotonated, oxidized metal complex MIIIL, and TEMPOH or tBu3PhOH. Solution equilibrium measurements for the reaction of [CoII(H2bim)3]2+ with TEMPO show a large, negative ground-state entropy for hydrogen atom transfer, −41 ± 2 cal mol−1 K−1. This is even more negative than the ΔSoHAT = −30 ± 2 cal mol−1 K−1 for the two iron complexes and the ΔSoHAT for RuII(acac)2(py-imH) + TEMPO, 4.9 ± 1.1 cal mol−1 K−1, as reported earlier. Calorimetric measurements quantitatively confirm the enthalpy of reaction for [FeII(H2bip)3]2+ + TEMPO, thus also confirming ΔSoHAT. Calorimetry on TEMPOH + tBu3PhO• gives ΔHoHAT = −11.2 ± 0.5 kcal mol−1 which matches the enthalpy predicted from the difference in literature solution BDEs. A brief evaluation of the literature thermochemistry of TEMPOH and tBu3PhOH supports the common assumption that ΔSoHAT ≈ 0 for HAT reactions of organic and small gas-phase molecules. However, this assumption does not hold for transition metal based HAT reactions. The trend in magnitude of |ΔSoHAT| for reactions with TEMPO, RuII(acac)2(py-imH) << [FeII(H2bip)3]2+ = [FeII(H2bim)3]2+ < [CoII(H2bim)3]2+, is surprisingly well predicted by the trends for electron transfer half-reaction entropies, ΔSoET, in aprotic solvents. This is because both ΔSoET and ΔSoHAT have substantial contributions from vibrational entropy, which varies significantly with the metal center involved. The close connection between ΔSoHAT and ΔSoET provides an important

  10. Relevance theory: pragmatics and cognition.

    PubMed

    Wearing, Catherine J

    2015-01-01

    Relevance Theory is a cognitively oriented theory of pragmatics, i.e., a theory of language use. It builds on the seminal work of H.P. Grice(1) to develop a pragmatic theory which is at once philosophically sensitive and empirically plausible (in both psychological and evolutionary terms). This entry reviews the central commitments and chief contributions of Relevance Theory, including its Gricean commitment to the centrality of intention-reading and inference in communication; the cognitively grounded notion of relevance which provides the mechanism for explaining pragmatic interpretation as an intention-driven, inferential process; and several key applications of the theory (lexical pragmatics, metaphor and irony, procedural meaning). Relevance Theory is an important contribution to our understanding of the pragmatics of communication. PMID:26263065

  11. Systems Biology

    SciTech Connect

    Wiley, H S.

    2006-06-01

    The biology revolution over the last 50 years has been driven by the ascendancy of molecular biology. This was enthusiastically embraced by most biologists because it took us into increasingly familiar territory. It took mysterious processes, such as the replication of genetic material and assigned them parts that could be readily understood by the human mind. When we think of ''molecular machines'' as being the underlying basis of life, we are using a paradigm derived from everyday experience. However, the price that we paid was a relentless drive towards reductionism and the attendant balkanization of biology. Now along comes ''systems biology'' that promises us a solution to the problem of ''knowing more and more about less and less''. Unlike molecular biology, systems biology appears to be taking us into unfamiliar intellectual territory, such as statistics, mathematics and computer modeling. Not surprisingly, systems biology has met with widespread skepticism and resistance. Why do we need systems biology anyway and how does this new area of research promise to change the face of biology in the next couple of decades?

  12. Metal-based 2,3-indolinedione derivatives as proteasome inhibitors and inducers of apoptosis in human cancer cells.

    PubMed

    Zhang, Pengfei; Bi, Caifeng; Schmitt, Sara M; Li, Xin; Fan, Yuhua; Zhang, Nan; Dou, Q Ping

    2014-09-01

    Proliferation and apoptotic pathways are tightly regulated in cells by the ubiquitin-proteasome system (UPS). Alterations in the UPS may result in cellular transformation or other pathological conditions. The proteasome is indeed often found to be overactive in cancer cells. It has been reported that 2,3-indolinedione (L), which exists in marine organisms, as well as in mammals, is a proteasome inhibitor. Studies have shown that metal-based complexes inhibit proteasome activity and induce apoptosis in certain human cancer cells. In the current study, we synthesized six novel metal-based complexes with derivatives of 2,3-indolinedione: [Cd (C15H11O3N2) (CH3COO)] (C1), [Cd (C15H11O2N2) (CH3COO)] (C2), [Co (C15H9O4N2) (CH3COO)] (C3), [Co (C15H11O2N2) (CH3COO)] (C4), [Zn (C19H14O3N3) (CH3COO)] (C5) and [Zn (C17H13O3N2) (CH3COO)] (C6). We sought to characterize and assess the proteasome inhibitory and anti-proliferative effects of these metal-based complexes in human breast (MDA-MB-231) and prostate (LNCaP and PC-3) cancer cells, in order to determine whether specific structures contribute to the inhibition of tumor proteasome activity and the induction of apoptosis. The results revealed that the complexes, C1, C3 and C5, but not their counterparts, C2, C4 and C6, inhibited the chymotrypsin-like activity of the human cancer cellular 26S proteasome; in addition, these complexes promoted the accumulation of the proteasome target protein, Bax, inhibited cell growth and induced apoptosis in a concentration- and time-dependent manner due to their unique structures. Our data suggest that the study of metal-based complexes, including aromatic ring structures with electron-attracting groups, may be an interesting research direction for the development of anticancer drugs. PMID:25017797

  13. Is synthetic biology mechanical biology?

    PubMed

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms. PMID:26205204

  14. The Concept of Relevance in IR.

    ERIC Educational Resources Information Center

    Borlund, Pia

    2003-01-01

    Introduces the concept of relevance as viewed and applied in the context of IR (information retrieval) evaluation by presenting an overview of the multidimensionality and dynamic nature of the concept. Topics include classes and types of relevance; relevance criteria; degrees of relevance; levels of relevance; situational relevance; and…

  15. The Upside to Hg-DOM Associations for Water Quality: Removal of Hg from Solution Using Coagulaion with Metal-Based Salts

    NASA Astrophysics Data System (ADS)

    Henneberry, Y.; Kraus, T. E.; Fleck, J.; Krabbenhoft, D. P.; Horwath, W. R.

    2011-12-01

    This study assessed the potential use of metal-based coagulants to remove dissolved mercury (Hg) from natural waters and provides information regarding the importance of Hg associations with the dissolved organic matter (DOM) fraction and metal hydroxides. Previous research indicated coagulants were not effective at removing Hg from solution; however those studies used high concentrations of Hg, which did not reflect naturally occurring concentrations of Hg. Filtered water collected from an agricultural drain in the Sacramento-San Joaquin Delta (Delta) was treated with three industrial-grade coagulants (ferric chloride, ferric sulfate, and polyaluminum chloride) to determine their efficacy in removing both inroganic (IHg) and methylmercury (MeHg) from the water column. The Delta suffers from elevated surface water Hg concentrations and as a result is listed as an imparied water body. Coagulants removed up to 85% of DOM from solution. In the absence of DOM, all three coagulants released IHg into solution, however in the presence of DOM the coagulants removed up to 97% of IHg and 80% of MeHg. Results suggest that the removal of Hg is mediated by DOM-coagulant interactions. There was a preferential association of IHg with the more aromatic, higher molecular weight fraction of DOM but no such relationship was found for MeHg. This study offers new fundamental insights regarding large-scale removal of Hg at environmentally relevant concentrations. Research using isotopically labeled Hg is providing insight into whether coagulation can remove recently added Hg (e.g. atmospheric deposition) from solution and whether once formed, the floc can remove additional Hg from the water column.

  16. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1978

    1978-01-01

    Presents experiments, demonstrations, activities and ideas relating to various fields of biology to be used in biology courses in secondary schools. Among those experiments presented are demonstrating the early stages of ferns and mosses and simple culture methods for fern prothalli. (HM)

  17. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including chi-square tests on a microcomputer, an integrated biology game, microscope slides of leaf stomata, culturing soil nematodes, technique for watering locust egg-laying tubes, hazards of biological chemicals (such as benzene, benzidene, calchicine,…

  18. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including use of dwarf cichlids (fishes) in secondary school biology, teaching edge effects on stomatal diffusion, computer program on effects of selection on gene frequencies, biological oxidation/reduction reactions, short cuts with Drosophila, computer program…

  19. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Presents procedures, exercises, demonstrations, and information on a variety of biology topics including labeling systems, biological indicators of stream pollution, growth of lichens, reproductive capacity of bulbous buttercups, a straw balance to measure transpiration, interaction of fungi, osmosis, and nitrogen fixation and crop production. (DC)

  20. Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

    PubMed Central

    Tovmasyan, Artak; Reboucas, Julio S.

    2014-01-01

    Abstract Significance: Half a century of research provided unambiguous proof that superoxide and species derived from it—reactive oxygen species (ROS)—play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential. Recent Advances: The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials. Critical Issues and Future Directions: Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution. Antioxid. Redox Signal. 20, 2416–2436. PMID:23964890

  1. Mathematical modeling relevant to closed artificial ecosystems

    USGS Publications Warehouse

    DeAngelis, D.L.

    2003-01-01

    The mathematical modeling of ecosystems has contributed much to the understanding of the dynamics of such systems. Ecosystems can include not only the natural variety, but also artificial systems designed and controlled by humans. These can range from agricultural systems and activated sludge plants, down to mesocosms, microcosms, and aquaria, which may have practical or research applications. Some purposes may require the design of systems that are completely closed, as far as material cycling is concerned. In all cases, mathematical modeling can help not only to understand the dynamics of the system, but also to design methods of control to keep the system operating in desired ranges. This paper reviews mathematical modeling relevant to the simulation and control of closed or semi-closed artificial ecosystems designed for biological production and recycling in applications in space. Published by Elsevier Science Ltd on behalf of COSPAR.

  2. Amyloid Polymorphism: Structural Basis and Neurobiological Relevance

    PubMed Central

    Tycko, Robert

    2015-01-01

    Summary Our understanding of the molecular structures of amyloid fibrils that are associated with neurodegenerative diseases, of mechanisms by which disease-associated peptides and proteins aggregate into fibrils, and of structural properties of aggregation intermediates has advanced considerably in recent years. Detailed molecular structural models for certain fibrils and aggregation intermediates are now available. It is now well established that amyloid fibrils are generally polymorphic at the molecular level, with a given peptide or protein being capable of forming a variety of distinct, self-propagating fibril structures. Recent results from structural studies and from studies involving cell cultures, transgenic animals, and human tissue provide initial evidence that molecular structural variations in amyloid fibrils and related aggregates may correlate with or even produce variations in disease development. This article reviews our current knowledge of the structural and mechanistic aspects of amyloid formation, as well as current evidence for the biological relevance of structural variations. PMID:25950632

  3. Current scenario of biomedical aspect of metal-based nanoparticles on gel dosimetry.

    PubMed

    Titus, Deena; Samuel, E James Jebaseelan; Mohana Roopan, Selvaraj

    2016-06-01

    In past decades, the possibility of using high atomic number nanoparticle has gained interest in gel dosimetry to enhance the dose deposited in the tumor while using low radiation as well as for better imaging purposes. Sparing of healthy tissues and targeting the tumor part have become much more captivating with the help of these systems. The gel dosimetry is a the three-dimensional dosimeter for extracting the dose, which can be used along with the nanoparticles like gold, platinum, and silver, for better therapeutic efficiency for modern radiotherapy techniques. These nanoparticles of different size prepared either by chemical route or green synthesis and incorporated into the gel system respond in a different manner. Having wide applications in therapeutic field, this study reviews the use of gel dosimeters in the therapeutic procedures and also with the aid of nanoparticles so as to achieve dose enhancement. The biological activity of the various nanoparticles has been discussed. PMID:27100529

  4. Contextualized Instruction: Teaching Relevant Behaviors in Relevant Contexts.

    ERIC Educational Resources Information Center

    Reboy, Lisa M.; Semb, George B.

    In contextualized instruction, the critical features of a context are considered important for the acquisition and transfer of a skill. Examples of contextualized instruction programs are Functional Context Education (FCE) and Anchored Instruction (AI). FCE involves the teaching of reading and mathematics skills in contexts that are relevant to…

  5. Biological clocks and the practice of psychiatry

    PubMed Central

    Schulz, Pierre

    2007-01-01

    Endogenous biological clocks enable living species to acquire some independence in relation to time. They improve the efficiency of biological systems, by allowing them to anticipate future constraints on major physyological systems and cell energy metabolism. The temporal organization of a giwen biological function can be impaired in its coordination with astronomical time or with other biological function. There are also external conditions that influence biological clocks. This temporal organization is complex, and it is possible that a series of psychiatric disorders and syndromes involve primary or secondary changes in biological clocks: seasonal and other mood disorders, premenstrual syndromes, social jet lag, free-running rhythms, and several sleep disorders are among them. In this review, we describe the main concepts relevant to chronobiology and explore the relevance of knowledge about biological clocks to the clinical practice of psychiatry PMID:17969862

  6. Interactions of metal-based engineered nanoparticles with aquatic higher plants: A review of the state of current knowledge.

    PubMed

    Thwala, Melusi; Klaine, Stephen J; Musee, Ndeke

    2016-07-01

    The rising potential for the release of engineered nanoparticles (ENPs) into aquatic environments requires evaluation of risks to protect ecological health. The present review examines knowledge pertaining to the interactions of metal-based ENPs with aquatic higher plants, identifies information gaps, and raises considerations for future research to advance knowledge on the subject. The discussion focuses on ENPs' bioaccessibility; uptake, adsorption, translocation, and bioaccumulation; and toxicity effects on aquatic higher plants. An information deficit surrounds the uptake of ENPs and associated dynamics, because the influence of ENP characteristics and water quality conditions has not been well documented. Dissolution appears to be a key mechanism driving bioaccumulation of ENPs, whereas nanoparticulates often adsorb to plant surfaces with minimal internalization. However, few reports document the internalization of ENPs by plants; thus, the role of nanoparticulates' internalization in bioaccumulation and toxicity remains unclear, requiring further investigation. The toxicities of metal-based ENPs mainly have been associated with dissolution as a predominant mechanism, although nano toxicity has also been reported. To advance knowledge in this domain, future investigations need to integrate the influence of ENP characteristics and water physicochemical parameters, as their interplay determines ENP bioaccessibility and influences their risk to health of aquatic higher plants. Furthermore, harmonization of test protocols is recommended for fast tracking the generation of comparable data. Environ Toxicol Chem 2016;35:1677-1694. © 2016 SETAC. PMID:26757140

  7. Mn in misch-metal based superlattice metal hydride alloy - Part 1 structural, hydrogen storage and electrochemical properties

    NASA Astrophysics Data System (ADS)

    Young, K.; Wong, D. F.; Wang, L.; Nei, J.; Ouchi, T.; Yasuoka, S.

    2015-03-01

    The structural, gaseous phase hydrogen storage, and electrochemical properties of a series of Mn-modified misch-metal based superlattice metal hydride alloys were investigated in part one of this two-part series of papers. X-ray diffraction analysis showed that these alloys are all multi-phased compositions with different abundances of AB2, AB3, A2B7, AB4, and AB5 phases. Substitution of Ni in the B-site by Mn promotes AB5 phase formation and decreases both gaseous phase and electrochemical capacities due to the reduction in the abundance of main hexagonal A2B7 phase. AC impedance and magnetic susceptibility measurement were employed to characterize the surface of Mn-free and Mn-modified alloys and show deterioration in surface catalytic ability as the Mn-content increases. Mn-modification adversely affected misch-metal based superlattice metal hydride alloy properties such as phase homogeneity, capacity, cycle stability, high-rate performance, and surface reaction.

  8. The Renaissance of Developmental Biology

    PubMed Central

    St Johnston, Daniel

    2015-01-01

    Since its heyday in the 1980s and 90s, the field of developmental biology has gone into decline; in part because it has been eclipsed by the rise of genomics and stem cell biology, and in part because it has seemed less pertinent in an era with so much focus on translational impact. In this essay, I argue that recent progress in genome-wide analyses and stem cell research, coupled with technological advances in imaging and genome editing, have created the conditions for the renaissance of a new wave of developmental biology with greater translational relevance. PMID:25946596

  9. Biological post

    PubMed Central

    Kumar, B. Suresh; Kumar, Senthil; Mohan Kumar, N. S.; Karunakaran, J. V.

    2015-01-01

    Anterior tooth fracture as a result of traumatic injuries, is frequently encountered in endodontic practice. Proper reconstruction of extensively damaged teeth can be achieved through the fragment reattachment procedure known as “biological restoration.” This case report refers to the esthetics and functional recovery of extensively damaged maxillary central incisor through the preparation and adhesive cementation of “biological post” in a young patient. Biological post obtained through extracted teeth from another individual–represent a low-cost option and alternative technique for the morphofunctional recovery of extensively damaged anterior teeth. PMID:26538952

  10. BIOLOGICAL WARFARE

    PubMed Central

    Beeston, John

    1953-01-01

    The use of biological agents as controlled weapons of war is practical although uncertain. Three types of agents are feasible, including pathogenic organisms and biological pests, toxins, and synthetic hormones regulating plant growth. These agents may be chosen for selective effects varying from prolonged incipient illness to death of plants, man and domestic animals. For specific preventive and control measures required to combat these situations, there must be careful and detailed planning. The nucleus of such a program is available within the existing framework of public health activities. Additional research and expansion of established activities in time of attack are necessary parts of biological warfare defense. PMID:13059641

  11. Relevance--There and Here

    ERIC Educational Resources Information Center

    Simon, Herbert A.

    1973-01-01

    Advocates that in the United States, as in China, scientific research receives government financial support essentially for utilitarian ends. Primary interest of the average citizen in research is not in acquiring knowledge but in its relevance to the needs of society. (JR)

  12. Medical Scenarios Relevant to Spaceflight

    NASA Technical Reports Server (NTRS)

    Bacal, Kira; Hurs, Victor; Doerr, Harold

    2004-01-01

    The Medical Operational Support Team (MOST) was tasked by the JSC Space Medicine and Life Sciences Directorate (SLSD) to incorporate medical simulation into 1) medical training for astronaut-crew medical officers (CMO) and medical flight control teams and 2) evaluations of procedures and resources required for medical care aboard the International Space Station (ISS). Development of evidence-based medical scenarios that mimic the physiology observed during spaceflight will be needed for the MOST to complete these two tasks. The MOST used a human patient simulator, the ISS-like resources in the Medical Simulation Laboratory (MSL), and evidence from space operations, military operations and medical literature to develop space relevant medical scenarios. These scenarios include conditions concerning airway management, Advanced Cardiac Life Support (ACLS) and mitigating anaphylactic symptoms. The MOST has used these space relevant medical scenarios to develop a preliminary space medical training regimen for NASA flight surgeons, Biomedical Flight Controllers (Biomedical Engineers; BME) and CMO-analogs. This regimen is conducted by the MOST in the MSL. The MOST has the capability to develop evidence-based space-relevant medical scenarios that can help SLSD I) demonstrate the proficiency of medical flight control teams to mitigate space-relevant medical events and 2) validate nextgeneration medical equipment and procedures for space medicine applications.

  13. Curricular Relevance in Teacher Education.

    ERIC Educational Resources Information Center

    Engbretson, William B.

    Major trends toward increasing curricular relevance in teacher education are discussed. These include concern for the education of teachers of disadvantaged youth and a return to the concept of early direct and laboratory experience programs exemplified in the San Francisco State College-Sausalito Teacher Education Project, STEP (see ED 023 633),…

  14. Culturally and Linguistically Relevant Readalouds

    ERIC Educational Resources Information Center

    May, Laura A.; Bingham, Gary E.; Pendergast, Meghan L.

    2014-01-01

    The teacher readaloud is an instructional tool established in its ability to foster children's language and literacy development. Increasing cultural and linguistic diversity and changing standards place pressure on teachers to provide literacy and language instruction relevant to children's everyday lives and learning. This article…

  15. Highly Stable Liquid Metal-Based Pressure Sensor Integrated with a Microfluidic Channel

    PubMed Central

    Jung, Taekeon; Yang, Sung

    2015-01-01

    Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30–1000 s−1. The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability. PMID:26007732

  16. Highly stable liquid metal-based pressure sensor integrated with a microfluidic channel.

    PubMed

    Jung, Taekeon; Yang, Sung

    2015-01-01

    Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30-1000 s(-1). The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability. PMID:26007732

  17. [Advance in the bioavailability monitoring of heavy metal based on microbial whole-cell sensor].

    PubMed

    Hou, Qi-Hui; Ma, An-Shou; Zhuang, Xiu-Liang; Zhuang, Guo-Qiang

    2013-01-01

    Microbial whole-cell biosensor is an excellent tool to assess the bioavailability of heavy metal in soil and water. However, the traditional physicochemical instruments are applied to detect the total metal. Furthermore, microbial whole-cell biosensor is simple, rapid and economical in manipulating, and is thus a highly qualified candidate for emergency detection of pollution incidents. The biological component of microbial whole-cell biosensor mostly consists of metalloregulatory proteins and reporter genes. In detail, metalloregulatory proteins mainly include the MerR family, ArsR family and RS family, and reporter genes mainly include gfp, lux and luc. Metalloregulatory protein and reporter gene are related to the sensitivity, specificity and properties in monitoring. The bioavailability of heavy metals is alterable under different conditions, influenced by pH, chelate and detection methods and so on. Increasing the accumulation of intracellular heavy metal, modifying the metalloregulatory proteins and optimizing the detecting conditions are important for improving the sensitivity, specificity and accuracy of the microbial whole-cell biosensor. The future direction of microbial whole-cell biosensor is to realize the monitoring of pollutions in situ and on line. PMID:23487961

  18. New metal based drugs: Spectral, electrochemical, DNA-binding, surface morphology and anticancer activity properties

    NASA Astrophysics Data System (ADS)

    Çeşme, Mustafa; Gölcü, Aysegul; Demirtaş, Ibrahim

    2015-01-01

    The NSAID piroxicam (PRX) drug was used for complex formation reactions with Cu(II), Zn(II) and Pt(II) metal salts have been synthesized. Then, these complexes have been characterized by spectroscopic and analytical techniques. Thermal behavior of the complexes were also investigated. The electrochemical properties of all complexes have been investigated by cyclic voltammetry (CV) using glassy carbon electrode. The biological activity of the complexes has been evaluated by examining their ability to bind to fish sperm double strand DNA (FSFSdsDNA) with UV spectroscopy. UV studies of the interaction of the PRX and its complexes with FSdsDNA have shown that these compounds can bind to FSdsDNA. The binding constants of the compounds with FSdsDNA have also been calculated. The morphology of the FSdsDNA, PRX, metal ions and metal complexes has been investigated by scanning electron microscopy (SEM). To get the SEM images, the interaction of compounds with FSdsDNA has been studied by means of differential pulse voltammetry (DPV) at FSdsDNA modified pencil graphite electrode (PGE). The decrease in intensity of the guanine oxidation signals has been used as an indicator for the interaction mechanism. The effect of proliferation PRX and complexes were examined on the HeLA and C6 cells using real-time cell analyzer with four different concentrations.

  19. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Ten ideas that have been tried out by the authors in schools are presented for biology teachers. The areas covered include genetics, dispersal of seeds, habituation in earthworms, respiration, sensory neurons, fats and oils. A reading list is provided. (PS)

  20. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1973

    1973-01-01

    Some helpful ideas are proposed for use by biology teachers. Topics included are Food Webs,'' Key to Identification of Families,'' Viruses,'' Sieve Tube,'' Woodlice,'' Ecology of Oak Leaf Roller Moth,'' and Model Making.'' (PS)

  1. Bottle Biology.

    ERIC Educational Resources Information Center

    CSTA Journal, 1995

    1995-01-01

    Provides hands-on biology activities using plastic bottles that allow students to become engaged in asking questions, creating experiments, testing hypotheses, and generating answers. Activities explore terrestrial and aquatic systems. (MKR)

  2. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Twelve new experiments in biology are described by teachers for use in classrooms. Broad areas covered include enzyme action, growth regulation, microscopy, respiration, germination, plant succession, leaf structure and blood structure. Explanations are detailed. (PS)

  3. Walking: technology and biology.

    PubMed

    Pfeiffer, Friedrich; Inoue, Hirochika

    2007-01-15

    If all the signs are to be believed, then the twenty-first century will technologically be characterized by machine walking and its relevant products, which possess all chances to become real bulk goods in the course of the next decades. With several university institutes and with Honda and Sony from the industrial side, Japan is today and without any doubt the leading nation in research and development of walking machines. The US and Europe follow at some distance. Walking machines will influence all areas of daily and industrial life and, with the fast evolution of artificial intelligence, will become a real partner of human beings. All relevant technologies are highly interdisciplinary, they will push the future technologies of all technical fields. The special issue on this topic gives a selection of walking machine research and development including some aspects from biology. PMID:17148046

  4. Biology of Pseudomonas stutzeri

    PubMed Central

    Lalucat, Jorge; Bennasar, Antoni; Bosch, Rafael; García-Valdés, Elena; Palleroni, Norberto J.

    2006-01-01

    Pseudomonas stutzeri is a nonfluorescent denitrifying bacterium widely distributed in the environment, and it has also been isolated as an opportunistic pathogen from humans. Over the past 15 years, much progress has been made in elucidating the taxonomy of this diverse taxonomical group, demonstrating the clonality of its populations. The species has received much attention because of its particular metabolic properties: it has been proposed as a model organism for denitrification studies; many strains have natural transformation properties, making it relevant for study of the transfer of genes in the environment; several strains are able to fix dinitrogen; and others participate in the degradation of pollutants or interact with toxic metals. This review considers the history of the discovery, nomenclatural changes, and early studies, together with the relevant biological and ecological properties, of P. stutzeri. PMID:16760312

  5. Biology of Immunoglobulins

    PubMed Central

    Berlot, Giorgio; Rossini, Perla; Turchet, Federica

    2015-01-01

    Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis in adult patients, in whom the current guidelines even recommend against their use, despite that many studies demonstrated either their beneficial effects in different subsets of patients and that some preparations of IvIg are more effective than other. The biology of Ig are reviewed, aiming to a more in-depth understanding of their properties in order to clarify their possible indications in different clinical settings. PMID:25674545

  6. 21 CFR 601.32 - General factors relevant to safety and effectiveness.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) BIOLOGICS LICENSING Diagnostic Radiopharmaceuticals § 601.32 General factors relevant to safety and effectiveness. FDA's determination of the safety and effectiveness of a diagnostic radiopharmaceutical includes consideration of the following: (a) The proposed use of the...

  7. 21 CFR 601.32 - General factors relevant to safety and effectiveness.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) BIOLOGICS LICENSING Diagnostic Radiopharmaceuticals § 601.32 General factors relevant to safety and effectiveness. FDA's determination of the safety and effectiveness of a diagnostic radiopharmaceutical includes consideration of the following: (a) The proposed use of the...

  8. 21 CFR 601.32 - General factors relevant to safety and effectiveness.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SERVICES (CONTINUED) BIOLOGICS LICENSING Diagnostic Radiopharmaceuticals § 601.32 General factors relevant to safety and effectiveness. FDA's determination of the safety and effectiveness of a diagnostic radiopharmaceutical includes consideration of the following: (a) The proposed use of the...

  9. Metal-based optical probes for live cell imaging of nitroxyl (HNO).

    PubMed

    Rivera-Fuentes, Pablo; Lippard, Stephen J

    2015-11-17

    Nitroxyl (HNO) is a biological signaling agent that displays distinctive reactivity compared to nitric oxide (NO). As a consequence, these two reactive nitrogen species trigger different physiological responses. Selective detection of HNO over NO has been a challenge for chemists, and several fluorogenic molecular probes have been recently developed with that goal in mind. Common constructs take advantage of the HNO-induced reduction of Cu(II) to Cu(I). The sensing mechanism of such probes relies on the ability of the unpaired electron in a d orbital of the Cu(II) center to quench the fluorescence of a photoemissive ligand by either an electron or energy transfer mechanism. Experimental and theoretical mechanistic studies suggest that proton-coupled electron transfer mediates this process, and careful tuning of the copper coordination environment has led to sensors with optimized selectivity and kinetics. The current optical probes cover the visible and near-infrared regions of the spectrum. This palette of sensors comprises structurally and functionally diverse fluorophores such as coumarin (blue/green emission), boron dipyrromethane (BODIPY, green emission), benzoresorufin (red emission), and dihydroxanthenes (near-infrared emission). Many of these sensors have been successfully applied to detect HNO production in live cells. For example, copper-based optical probes have been used to detect HNO production in live mammalian cells that have been treated with H2S and various nitrosating agents. These studies have established a link between HSNO, the smallest S-nitrosothiol, and HNO. In addition, a near-infrared HNO sensor has been used to perform multicolor/multianalyte microscopy, revealing that exogenously applied HNO elevates the concentration of intracellular mobile zinc. This mobilization of zinc ions is presumably a consequence of nitrosation of cysteine residues in zinc-chelating proteins such as metallothionein. Future challenges for the optical imaging of

  10. Crossing Boundaries in Undergraduate Biology Education

    ERIC Educational Resources Information Center

    Vanderklein, Dirk; Munakata, Mika; McManus, Jason

    2016-01-01

    In an effort to make mathematics relevant to biology students, the authors developed two modules that sought to integrate mathematics and ecology instruction to differing degrees. The modules were developed by a team of biology and mathematics educators and were implemented in an ecology course using three different instructional methods for three…

  11. Exemplary Programs in Secondary School Biology.

    ERIC Educational Resources Information Center

    McComas, William F.; Penick, John E.

    1989-01-01

    Summarizes 10 exemplary programs which address topics on individualized biology, a modified team approach, limnology, physical anthropology, the relevance of biology to society, ecology, and health. Provides names and addresses of contact persons for further information. Units cover a broad range of abilities and activities. (RT)

  12. Biological Correlates of Intimate Partner Violence Perpetration

    PubMed Central

    Pinto, Lavinia A.; Sullivan, Eric L.; Rosenbaum, Alan; Wyngarden, Nicole; Umhau, John C.; Miller, Mark W.; Taft, Casey T.

    2013-01-01

    An extensive literature documents biological correlates of general aggression, but there has been less focus on biological correlates of intimate partner violence (IPV). The purpose of this review is to summarize the research literature to date that has reported on biological factors in IPV perpetration. We review the existing literature on four domains of biological processes that have been examined with respect to IPV perpetration, including: head injury and neuropsychology; psychophysiology; neurochemistry, metabolism and endocrinology; and genetics. We critique the literature, discuss the clinical relevance of research findings, and provide some recommendations for future biologically-oriented IPV research. PMID:23393423

  13. Relevance of rhodopsin studies for GPCR activation.

    PubMed

    Deupi, Xavier

    2014-05-01

    GPCRs, or the most detailed analysis of cellular GPCR signal transduction networks using a systems biology approach, have been carried out in rhodopsin. Finally, due again to its unique properties among GPCRs, rhodopsin will likely play an important role in the application of X-ray free electron laser crystallography to time-resolved structural biology in membrane proteins. Rhodopsin, thus, still remains relevant as a model system to study the molecular mechanisms of GPCR activation. This article is part of a Special Issue entitled: Retinal Proteins-You can teach an old dog new tricks. PMID:24041646

  14. Biological Oceanography

    NASA Technical Reports Server (NTRS)

    Abbott, M. R.

    1984-01-01

    Within the framework of global biogeochemical cycles and ocean productivity, there are two areas that will be of particular interest to biological oceanography in the 1990s. The first is the mapping in space time of the biomass and productivity of phytoplankton in the world ocean. The second area is the coupling of biological and physical processes as it affects the distribution and growth rate of phytoplankton biomass. Certainly other areas will be of interest to biological oceanographers, but these two areas are amenable to observations from satellites. Temporal and spatial variability is a regular feature of marine ecosystems. The temporal and spatial variability of phytoplankton biomass and productivity which is ubiquitous at all time and space scales in the ocean must be characterized. Remote sensing from satellites addresses these problems with global observations of mesocale (2 to 20 days, 10 to 200 km) features over a long period of time.

  15. Biological preconcentrator

    DOEpatents

    Manginell, Ronald P.; Bunker, Bruce C.; Huber, Dale L.

    2008-09-09

    A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

  16. Biological rhythms

    NASA Technical Reports Server (NTRS)

    Halberg, F.

    1975-01-01

    An overview is given of basic features of biological rhythms. The classification of periodic behavior of physical and psychological characteristics as circadian, circannual, diurnal, and ultradian is discussed, and the notion of relativistic time as it applies in biology is examined. Special attention is given to circadian rhythms which are dependent on the adrenocortical cycle. The need for adequate understanding of circadian variations in the basic physiological indicators of an individual (heart rate, body temperature, systolic and diastolic blood pressure, etc.) to ensure the effectiveness of prophylactic and therapeutic measures is stressed.

  17. Literature relevant to remote sensing of water quality

    NASA Technical Reports Server (NTRS)

    Middleton, E. M.; Marcell, R. F.

    1983-01-01

    References relevant to remote sensing of water quality were compiled, organized, and cross-referenced. The following general categories were included: (1) optical properties and measurement of water characteristics; (2) interpretation of water characteristics by remote sensing, including color, transparency, suspended or dissolved inorganic matter, biological materials, and temperature; (3) application of remote sensing for water quality monitoring; (4) application of remote sensing according to water body type; and (5) manipulation, processing and interpretation of remote sensing digital water data.

  18. Relevance of nutrient media composition for hydrogen production in Chlamydomonas.

    PubMed

    Gonzalez-Ballester, David; Jurado-Oller, Jose Luis; Fernandez, Emilio

    2015-09-01

    Microalgae are capable of biological H2 photoproduction from water, solar energy, and a variety of organic substrates. Acclimation responses to different nutrient regimes finely control photosynthetic activity and can influence H2 production. Hence, nutrient stresses are an interesting scenario to study H2 production in photosynthetic organisms. In this review, we mainly focus on the H2-production mechanisms in Chlamydomonas reinhardtii and the physiological relevance of the nutrient media composition when producing H2. PMID:25952745

  19. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1980

    1980-01-01

    Describes equipment, activities, and experiments useful in biology and environmental education instruction, including, among others, sampling in ecology using an overhead projector, the slide finder as an aid to microscopy, teaching kidney function, and teaching wildlife conservation-sand dune systems. (SK)

  20. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1984

    1984-01-01

    Presents information on the teaching of nutrition (including new information relating to many current O-level syllabi) and part 16 of a reading list for A- and S-level biology. Also includes a note on using earthworms as a source of material for teaching meiosis. (JN)

  1. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Presents content information and/or laboratory procedures and experiments on different biology topics including small-scale cultivation of watercress and its use in water-culture experiments, microbiology of the phylloplane, use of mouthbrooders in science class, and the gene. (DC)

  2. Scaffolded biology.

    PubMed

    Minelli, Alessandro

    2016-09-01

    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology. PMID:27287514

  3. Cancer Biology

    ERIC Educational Resources Information Center

    Dominiecki, Mary E.

    2004-01-01

    University of Colorado's Virtual Student Fellowship available at and developed by Bakemeier, Richard F. This website is designed to give students applying for a fellowship an overview of basic topics in biology and how they are used by cancer researchers to develop new treatments.

  4. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1976

    1976-01-01

    Describes nine biology experiments, including osmosis, genetics; oxygen content of blood, enzymes in bean seedlings, preparation of bird skins, vascularization in bean seedlings, a game called "sequences" (applied to review situations), crossword puzzle for human respiration, and physiology of the woodlouse. (CS)

  5. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1979

    1979-01-01

    Organized by topic is a reading list for A- and S-level biology. Described are experiments for measuring rate of water uptake in a shoot; questions to aid students in designing experiments; rise of overhead projection to demonstrate osmosis and blood cell counting; and microbial manufacture of vinegar. (CS)

  6. Marine Biology

    ERIC Educational Resources Information Center

    Dewees, Christopher M.; Hooper, Jon K.

    1976-01-01

    A variety of informational material for a course in marine biology or oceanology at the secondary level is presented. Among the topics discussed are: food webs and pyramids, planktonic blooms, marine life, plankton nets, food chains, phytoplankton, zooplankton, larval plankton and filter feeders. (BT)

  7. (Biological dosimetry)

    SciTech Connect

    Preston, R.J.

    1990-12-17

    The traveler attended the 1st International Conference on Biological Dosimetry in Madrid, Spain. This conference was organized to provide information to a general audience of biologists, physicists, radiotherapists, industrial hygiene personnel and individuals from related fields on the current ability of cytogenetic analysis to provide estimates of radiation dose in cases of occupational or environmental exposure. There is a growing interest in Spain in biological dosimetry because of the increased use of radiation sources for medical and occupational uses, and with this the anticipated and actual increase in numbers of overexposure. The traveler delivered the introductory lecture on Biological Dosimetry: Mechanistic Concepts'' that was intended to provide a framework by which the more applied lectures could be interpreted in a mechanistic way. A second component of the trip was to provide advice with regard to several recent cases of overexposure that had been or were being assessed by the Radiopathology and Radiotherapy Department of the Hospital General Gregorio Maranon'' in Madrid. The traveler had provided information on several of these, and had analyzed cells from some exposed or purportedly exposed individuals. The members of the biological dosimetry group were referred to individuals at REACTS at Oak Ridge Associated Universities for advice on follow-up treatment.

  8. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Outlines a variety of laboratory procedures, techniques, and materials including construction of a survey frame for field biology, a simple tidal system, isolation and applications of plant protoplasts, tropisms, teaching lung structure, and a key to statistical methods for biologists. (DS)

  9. Bottle Biology.

    ERIC Educational Resources Information Center

    Jager, Peter

    1993-01-01

    Describes activities which utilize plastic drink bottles and are designed to foster the development of a wide range of biological and ecological concepts. Includes instructions for making a model compost column and presents a model that illustrates open versus closed ecosystems. (DDR)

  10. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including water relation exercise on auxin-treated artichoke tuber tissue; aerobic respiration in yeast; an improved potometer; use of mobiles in biological classification, and experiments on powdery mildews and banana polyphenol oxidase. Includes reading lists…

  11. Microdosing: Concept, Application and Relevance

    PubMed Central

    Tewari, Tushar; Mukherjee, Shoibal

    2010-01-01

    The use of microdose pharmacokinetic studies as an essential tool in drug development is still to catch on. While this approach promises potential cost savings and a quantum leap in efficiencies of the drug development process, major hurdles still need to be overcome before the technique becomes commonplace and part of routine practice. Clear regulations in Europe and the USA have had an enabling effect. The lack of enabling provisions for microdosing studies in Indian regulation, despite low risk and manifest relevance for the local drug development industry, is inconsistent with the country's aspirations to be among the leaders in pharmaceutical research. PMID:21829784

  12. The Asian Eyelid: Relevant Anatomy

    PubMed Central

    Kiranantawat, Kidakorn; Suhk, Jeong Hoon; Nguyen, Anh H.

    2015-01-01

    The eyelid of Asians has its own unique characteristics. If the surgeon does not acknowledge this, aesthetically pleasing results will seldom be achieved. Here the authors review and summarize important up-to-date anatomical and relevant clinical studies of the Asian upper eyelid, aiming to help surgeons thoroughly understand its unique features, including Asian eyelid morphology, anatomical details, and the mechanisms of upper eyelid crease formation. Hopefully, an in-depth understanding of the Asian eyelid will aid surgeons to accomplish their work and lead to novel new techniques in this field. PMID:26306082

  13. The self-relevance system?

    PubMed

    Conway, Martin A; Pothos, Emmanuel M; Turk, David J

    2016-01-01

    We suggest that the Self Attention Network (SAN) maybe part of a larger self-regulatory system, which we term the Self-Relevance System (SRS) of which the "core" or default network is a major part. It is within the core network that memories are generated and the future imagined. Such memories and imaginings are the basis of preoccupations. Within the SRS then preoccupations drive the emergence of attentional biases (ABs). ABs in turn are modulated by the SAN activating and inhibiting circuits that shape behavior. We consider briefly how this might function in dysfunctional appetitive behaviors, e.g., substance abuse. PMID:26305290

  14. Biological trade and markets

    PubMed Central

    2016-01-01

    Cooperation between organisms can often be understood, like trade between merchants, as a mutually beneficial exchange of services, resources or other ‘commodities’. Mutual benefits alone, however, are not sufficient to explain the evolution of trade-based cooperation. First, organisms may reject a particular trade if another partner offers a better deal. Second, while human trade often entails binding contracts, non-human trade requires unwritten ‘terms of contract’ that ‘self-stabilize’ trade and prevent cheating even if all traders strive to maximize fitness. Whenever trading partners can be chosen, market-like situations arise in nature that biologists studying cooperation need to account for. The mere possibility of exerting partner choice stabilizes many forms of otherwise cheatable trade, induces competition, facilitates the evolution of specialization and often leads to intricate forms of cooperation. We discuss selected examples to illustrate these general points and review basic conceptual approaches that are important in the theory of biological trade and markets. Comparing these approaches with theory in economics, it turns out that conventional models—often called ‘Walrasian’ markets—are of limited relevance to biology. In contrast, early approaches to trade and markets, as found in the works of Ricardo and Cournot, contain elements of thought that have inspired useful models in biology. For example, the concept of comparative advantage has biological applications in trade, signalling and ecological competition. We also see convergence between post-Walrasian economics and biological markets. For example, both economists and biologists are studying ‘principal–agent’ problems with principals offering jobs to agents without being sure that the agents will do a proper job. Finally, we show that mating markets have many peculiarities not shared with conventional economic markets. Ideas from economics are useful for biologists

  15. Biological trade and markets.

    PubMed

    Hammerstein, Peter; Noë, Ronald

    2016-02-01

    Cooperation between organisms can often be understood, like trade between merchants, as a mutually beneficial exchange of services, resources or other 'commodities'. Mutual benefits alone, however, are not sufficient to explain the evolution of trade-based cooperation. First, organisms may reject a particular trade if another partner offers a better deal. Second, while human trade often entails binding contracts, non-human trade requires unwritten 'terms of contract' that 'self-stabilize' trade and prevent cheating even if all traders strive to maximize fitness. Whenever trading partners can be chosen, market-like situations arise in nature that biologists studying cooperation need to account for. The mere possibility of exerting partner choice stabilizes many forms of otherwise cheatable trade, induces competition, facilitates the evolution of specialization and often leads to intricate forms of cooperation. We discuss selected examples to illustrate these general points and review basic conceptual approaches that are important in the theory of biological trade and markets. Comparing these approaches with theory in economics, it turns out that conventional models-often called 'Walrasian' markets-are of limited relevance to biology. In contrast, early approaches to trade and markets, as found in the works of Ricardo and Cournot, contain elements of thought that have inspired useful models in biology. For example, the concept of comparative advantage has biological applications in trade, signalling and ecological competition. We also see convergence between post-Walrasian economics and biological markets. For example, both economists and biologists are studying 'principal-agent' problems with principals offering jobs to agents without being sure that the agents will do a proper job. Finally, we show that mating markets have many peculiarities not shared with conventional economic markets. Ideas from economics are useful for biologists studying cooperation but need

  16. Interactive Effects of Working Memory Self-Regulatory Ability and Relevance Instructions on Text Processing

    ERIC Educational Resources Information Center

    Hamilton, Nancy Jo

    2012-01-01

    Reading is a process that requires the enactment of many cognitive processes. Each of these processes uses a certain amount of working memory resources, which are severely constrained by biology. More efficiency in the function of working memory may mediate the biological limits of same. Reading relevancy instructions may be one such method to…

  17. The Constraints of Relevance on Prevocational Curriculum

    ERIC Educational Resources Information Center

    Doherty, Catherine

    2015-01-01

    This paper reflects on how relevance has been invoked as a curricular principle, both by students and teachers, in curriculum documents and in curriculum theory, to explore its variously conceived parameters and conditions. By posing the questions "relevant to whom?", "relevant to what?", "relevant how?" and…

  18. The Need for Culturally Relevant Dance Education

    ERIC Educational Resources Information Center

    McCarthy-Brown, Nyama

    2009-01-01

    There is a need for culturally relevant teaching in dance education. Many dance teachers have heard the buzz words "culturally relevant teaching methods." Yet these dance educators acknowledge that the "dance culture" is not always synonymous with "culturally relevant." This paper examines the issue of culturally relevant teaching methods in dance…

  19. Interaction of dermatologically relevant nanoparticles with skin cells and skin

    PubMed Central

    Rancan, Fiorenza; Ahlberg, Sebastian; Nazemi, Berouz; Choe, Chun Sik; Darvin, Maxim E; Hadam, Sabrina; Blume-Peytavi, Ulrike; Loza, Kateryna; Diendorf, Jörg; Epple, Matthias; Graf, Christina; Rühl, Eckart; Meinke, Martina C; Lademann, Jürgen

    2014-01-01

    Summary The investigation of nanoparticle interactions with tissues is complex. High levels of standardization, ideally testing of different material types in the same biological model, and combinations of sensitive imaging and detection methods are required. Here, we present our studies on nanoparticle interactions with skin, skin cells, and biological media. Silica, titanium dioxide and silver particles were chosen as representative examples for different types of skin exposure to nanomaterials, e.g., unintended environmental exposure (silica) versus intended exposure through application of sunscreen (titanium dioxide) or antiseptics (silver). Because each particle type exhibits specific physicochemical properties, we were able to apply different combinations of methods to examine skin penetration and cellular uptake, including optical microscopy, electron microscopy, X-ray microscopy on cells and tissue sections, flow cytometry of isolated skin cells as well as Raman microscopy on whole tissue blocks. In order to assess the biological relevance of such findings, cell viability and free radical production were monitored on cells and in whole tissue samples. The combination of technologies and the joint discussion of results enabled us to look at nanoparticle–skin interactions and the biological relevance of our findings from different angles. PMID:25551064

  20. Marine biology

    SciTech Connect

    Thurman, H.V.; Webber, H.H.

    1984-01-01

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index.

  1. Macromolecules Relevant to Stone Formation

    NASA Astrophysics Data System (ADS)

    Ryall, Rosemary L.; Cook, Alison F.; Thurgood, Lauren A.; Grover, Phulwinder K.

    2007-04-01

    Despite years of research, no single macromolecule in kidney calculi or in urine has yet been shown to fulfill a specific function in stone pathogenesis. In this paper we briefly review papers investigating the urinary excretion of individual macromolecules, their effects on calcium oxalate (CaOx) crystallization and attachment of crystals to renal epithelial cells, and the influence of lithogenic conditions on their renal expression in cultured cells and animal models. Using prothrombin fragment 1 (PTF1) and human serum albumin as examples, we show the types of patterns resulting from the binding of a fluorescently tagged protein to a specific CaOx monohydrate (COM) crystal face and its incorporation into the crystal structure. Molecular modeling is also used to illustrate how PTF1 can align with the atomic array on a COM crystal surface. We conclude that although many macromolecules are, by strict definition, relevant to stone formation, very few are probably truly influential.

  2. Ancient "Observatories" - A Relevant Concept?

    NASA Astrophysics Data System (ADS)

    Belmonte, Juan Antonio

    It is quite common, when reading popular books on astronomy, to see a place referred to as "the oldest observatory in the world". In addition, numerous books on archaeoastronomy, of various levels of quality, frequently refer to the existence of "prehistoric" or "ancient" observatories when describing or citing monuments that were certainly not built with the primary purpose of observing the skies. Internet sources are also guilty of this practice. In this chapter, the different meanings of the word observatory will be analyzed, looking at how their significances can be easily confused or even interchanged. The proclaimed "ancient observatories" are a typical result of this situation. Finally, the relevance of the concept of the ancient observatory will be evaluated.

  3. Mars simulations relevant to planetary protection

    NASA Astrophysics Data System (ADS)

    Ehrenfreund, P.; Garry, J.; ten Kate, I.; Norberg, P.; van Sluis, K.

    We have recently investigated the native amino acid composition of two analogs of martian soil JSC-1 and Salten Skov A Mars simulation chamber has been built and used to expose samples of these analogs to temperature and lighting conditions similar to those found at low-latitudes on the martian surface We have quantified the amino acid content of these two martian regolith simulants using high performance liquid chromatography HPLC In doing so we have obtained data that are useful for biological chemical and physical studies of analogs to martian surface materials We have also investigated the influence of UV radiation low temperatures and gaseous CO 2 on the intrinsic amino acid composition of both martian soil analogs Exposure to energetic ultraviolet light in vacuum appears to cause a modest increase in the concentration of certain amino acids within the materials which has been interpreted as resulting from the degradation of microorganisms The influence of low temperatures shows that the accretion of condensed water on the soils leads to the destruction of amino acids supporting the idea that reactive chemical processes involving H 2 O are at work within the martian soil analogs We also tested the radiation resistance of Natronorubrum sp HG-1 halophilic bacteria in air and repeated those experiments in the Mars simulation chamber by mixing the halophilic microbe into martian regolith analogs In this paper we discuss the relevance of Mars simulations for life detection and for planetary protection issues

  4. Fractals in biology and medicine

    NASA Technical Reports Server (NTRS)

    Havlin, S.; Buldyrev, S. V.; Goldberger, A. L.; Mantegna, R. N.; Ossadnik, S. M.; Peng, C. K.; Simons, M.; Stanley, H. E.

    1995-01-01

    Our purpose is to describe some recent progress in applying fractal concepts to systems of relevance to biology and medicine. We review several biological systems characterized by fractal geometry, with a particular focus on the long-range power-law correlations found recently in DNA sequences containing noncoding material. Furthermore, we discuss the finding that the exponent alpha quantifying these long-range correlations ("fractal complexity") is smaller for coding than for noncoding sequences. We also discuss the application of fractal scaling analysis to the dynamics of heartbeat regulation, and report the recent finding that the normal heart is characterized by long-range "anticorrelations" which are absent in the diseased heart.

  5. The NASA Space Biology Program

    NASA Technical Reports Server (NTRS)

    Halstead, T. W.

    1982-01-01

    A discussion is presented of the research conducted under the auspices of the NASA Space Biology Program. The objectives of this Program include the determination of how gravity affects and how it has shaped life on earth, the use of gravity as a tool to investigate relevant biological questions, and obtaining an understanding of how near-weightlessness affects both plants and animals in order to enhance the capability to use and explore space. Several areas of current developmental research are discussed and the future focus of the Program is considered.

  6. The meaning of biological information

    PubMed Central

    Koonin, Eugene V.

    2016-01-01

    Biological information encoded in genomes is fundamentally different from and effectively orthogonal to Shannon entropy. The biologically relevant concept of information has to do with ‘meaning’, i.e. encoding various biological functions with various degree of evolutionary conservation. Apart from direct experimentation, the meaning, or biological information content, can be extracted and quantified from alignments of homologous nucleotide or amino acid sequences but generally not from a single sequence, using appropriately modified information theoretical formulae. For short, information encoded in genomes is defined vertically but not horizontally. Informally but substantially, biological information density seems to be equivalent to ‘meaning’ of genomic sequences that spans the entire range from sharply defined, universal meaning to effective meaninglessness. Large fractions of genomes, up to 90% in some plants, belong within the domain of fuzzy meaning. The sequences with fuzzy meaning can be recruited for various functions, with the meaning subsequently fixed, and also could perform generic functional roles that do not require sequence conservation. Biological meaning is continuously transferred between the genomes of selfish elements and hosts in the process of their coevolution. Thus, in order to adequately describe genome function and evolution, the concepts of information theory have to be adapted to incorporate the notion of meaning that is central to biology. PMID:26857678

  7. The meaning of biological information.

    PubMed

    Koonin, Eugene V

    2016-03-13

    Biological information encoded in genomes is fundamentally different from and effectively orthogonal to Shannon entropy. The biologically relevant concept of information has to do with 'meaning', i.e. encoding various biological functions with various degree of evolutionary conservation. Apart from direct experimentation, the meaning, or biological information content, can be extracted and quantified from alignments of homologous nucleotide or amino acid sequences but generally not from a single sequence, using appropriately modified information theoretical formulae. For short, information encoded in genomes is defined vertically but not horizontally. Informally but substantially, biological information density seems to be equivalent to 'meaning' of genomic sequences that spans the entire range from sharply defined, universal meaning to effective meaninglessness. Large fractions of genomes, up to 90% in some plants, belong within the domain of fuzzy meaning. The sequences with fuzzy meaning can be recruited for various functions, with the meaning subsequently fixed, and also could perform generic functional roles that do not require sequence conservation. Biological meaning is continuously transferred between the genomes of selfish elements and hosts in the process of their coevolution. Thus, in order to adequately describe genome function and evolution, the concepts of information theory have to be adapted to incorporate the notion of meaning that is central to biology. PMID:26857678

  8. Metal-based nanoparticle interactions with the nervous system: The challenge of brain entry and the risk of retention in the organism

    EPA Science Inventory

    This review of metal and metal-oxide based nanoparticles focuses on factors that influence their distribution into the nervous system, evidence that they enter brain parenchyma, and nervous system responses. Emphasis is placed on gold as a model metal-based nanoparticle and for r...

  9. Copper: Toxicological relevance and mechanisms

    PubMed Central

    Gaetke, Lisa M.; Chow-Johnson, Hannah S.; Chow, Ching K.

    2015-01-01

    Copper (Cu) is a vital mineral essential for many biological processes. The vast majority of all Cu in healthy humans is associated with enzyme prosthetic groups or bound to proteins. Cu homeostasis is tightly regulated through a complex system of Cu transporters and chaperone proteins. Excess or toxicity of Cu, which is associated with the pathogenesis of hepatic disorder, neurodegenerative changes and other disease conditions, can occur when Cu homeostasis is disrupted. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced cellular toxicity. Recently, altered cellular events, including lipid metabolism, gene expression, alpha-synuclein aggregation, activation of acidic sphingomyelinase and release of ceramide, and temporal and spatial distribution of Cu in hepatocytes, as well as Cu-protein interaction in the nerve system, have been suggested to play a role in Cu toxicity. However, whether these changes are independent of, or secondary to, an altered cellular redox state of Cu remain to be elucidated. PMID:25199685

  10. Bridging Physics and Biology Using Resistance and Axons

    ERIC Educational Resources Information Center

    Dyer, Joshua M.

    2014-01-01

    When teaching physics, it is often difficult to get biology-oriented students to see the relevance of physics. A complaint often heard is that biology students are required to take physics for the Medical College Admission Test (MCAT) as part of a "weeding out" process, but that they don't feel like they need physics for biology.…

  11. IQ Predicts Biological Motion Perception in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rutherford, M. D.; Troje, Nikolaus F.

    2012-01-01

    Biological motion is easily perceived by neurotypical observers when encoded in point-light displays. Some but not all relevant research shows significant deficits in biological motion perception among those with ASD, especially with respect to emotional displays. We tested adults with and without ASD on the perception of masked biological motion…

  12. Green and selective polycondensation methods toward linear sorbitol-based polyesters: enzymatic versus organic and metal-based catalysis.

    PubMed

    Gustini, Liliana; Lavilla, Cristina; Janssen, William W T J; Martínez de Ilarduya, Antxon; Muñoz-Guerra, Sebastián; Koning, Cor E

    2016-08-23

    Renewable polyesters derived from a sugar alcohol (i.e., sorbitol) were synthesized by solvent-free polycondensation. The aim was to prepare linear polyesters with pendant hydroxyl groups along the polymer backbone. The performance of the sustainable biocatalyst SPRIN liposorb CALB [an immobilized form of Candida antarctica lipase B (CALB); SPRIN technologies] and the organo-base catalyst 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) were compared with two metal-based catalysts: dibutyl tin oxide (DBTO) and scandium trifluoromethanesulfonate [also known as scandium triflate, Sc(OTf)3 ]. For the four catalytic systems, the efficiency and selectivity for the incorporation of sorbitol were studied, mainly using (13) C and (31) P NMR spectroscopies, whereas side reactions, such as ether formation and dehydration of sorbitol, were evaluated using MALDI-TOF-MS. Especially the biocatalyst SPRIN liposorb CALB succeeded in incorporating sorbitol in a selective way without side reactions, leading to close-to-linear polyesters. By using a renewable hydroxyl-reactive curing agent based on l-lysine, transparent and glossy poly(ester urethane) networks were successfully synthesized offering a tangible example of bio-based coatings. PMID:27406029

  13. Noble metal-based bimetallic nanoparticles: the effect of the structure on the optical, catalytic and photocatalytic properties.

    PubMed

    Zaleska-Medynska, Adriana; Marchelek, Martyna; Diak, Magdalena; Grabowska, Ewelina

    2016-03-01

    Nanoparticles composed of two different metal elements show novel electronic, optical, catalytic or photocatalytic properties from monometallic nanoparticles. Bimetallic nanoparticles could show not only the combination of the properties related to the presence of two individual metals, but also new properties due to a synergy between two metals. The structure of bimetallic nanoparticles can be oriented in random alloy, alloy with an intermetallic compound, cluster-in-cluster or core-shell structures and is strictly dependent on the relative strengths of metal-metal bond, surface energies of bulk elements, relative atomic sizes, preparation method and conditions, etc. In this review, selected properties, such as structure, optical, catalytic and photocatalytic of noble metals-based bimetallic nanoparticles, are discussed together with preparation routes. The effects of preparation method conditions as well as metal properties on the final structure of bimetallic nanoparticles (from alloy to core-shell structure) are followed. The role of bimetallic nanoparticles in heterogeneous catalysis and photocatalysis are discussed. Furthermore, structure and optical characteristics of bimetallic nanoparticles are described in relation to the some features of monometallic NPs. Such a complex approach allows to systematize knowledge and to identify the future direction of research. PMID:26805520

  14. The effect of abrasive blasting on the strength of a joint between dental porcelain and metal base.

    PubMed

    Pietnicki, Krzysztof; Wołowiec, Emilia; Klimek, Leszek

    2014-01-01

    This paper presents the effect of selected parameters of abrasive blasting on the strength of a joint between dental porcelain and metal base. Experiments were conducted for different grain sizes of abrasive material and different blasting angles, with a constant blasting pressure. InLine dental porcelain was fused on samples of cobalt-chromium alloy following abrasive blasting; they were subsequently subjected to shearing forces on a testing machine. The fractures were observed under an electron scanning microscope in order to determine the character and course of fracturing. Strength tests showed that the grain size of abrasive material was a parameter with the greatest effect on the strength. The best effects were achieved for samples subjected to abrasive blasting with material with grain size of 110 μm. No statistically significant differences were found for the strength of samples worked at different angles. The results of the fractographic examinations have shown that in all the samples, fracturing occurred mainly along the porcelain-metal boundary, with few cases of fracturing through porcelain. PMID:24708248

  15. Grand challenges in space synthetic biology.

    PubMed

    Menezes, Amor A; Montague, Michael G; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-12-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

  16. Grand challenges in space synthetic biology

    PubMed Central

    Montague, Michael G.; Cumbers, John; Hogan, John A.

    2015-01-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

  17. Land Biology

    NASA Technical Reports Server (NTRS)

    Kanemasu, E. T.

    1984-01-01

    The advancing technology of our civilization on Earth affects our environment on a local, regional and global scale. Local effects can feed into larger scale effects because of positive feedbacks in our system. The ability to understand, quantify and predict the large scale and long-term effects of technology is truly mind boggling. The understanding of these effects, which is paramount to the quality of life on Earth, will depend upon the ability to interact with scientists from the biological, atmospheric, oceanographic and geological sciences and develop a common communication system and unified objectives.

  18. On Relevance Weight Estimation and Query Expansion.

    ERIC Educational Resources Information Center

    Robertson, S. E.

    1986-01-01

    A Bayesian argument is used to suggest modifications to the Robertson and Jones relevance weighting formula to accommodate the addition to the query of terms taken from the relevant documents identified during the search. (Author)

  19. Laboratory Animal Medicine: Teaching for Relevance

    ERIC Educational Resources Information Center

    Harkness, J. E.

    1977-01-01

    A mechanism for augmenting the relevance of instruction in laboratory animal medicine is suggested: the identification of practice-relevant content. This identification helps foster a positive attitude toward the subject and facilitates the retention of information. (LBH)

  20. Detoxification reactions: relevance to aging

    PubMed Central

    Zimniak, Piotr

    2008-01-01

    It is widely (although not universally) accepted that organismal aging is the result of two opposing forces: (i) processes that destabilize the organism and increase the probability of death, and (ii) longevity assurance mechanisms that prevent, repair, or contain damage. Processes of the first group are often chemical and physico-chemical in nature, and are either inevitable or only under marginal biological control. In contrast, protective mechanisms are genetically determined and are subject to natural selection. Life span is therefore largely dependent on the investment into protective mechanisms which evolve to optimize reproductive fitness. Recent data indicate that toxicants, both environmental and generated endogenously by metabolism, are major contributors to macromolecular damage and physiological dysregulation that contribute to aging; electrophilic carbonyl compounds derived from lipid peroxidation appear to be particularly important. As a consequence, detoxification mechanisms, including the removal of electrophiles by glutathione transferase-catalyzed conjugation, are major longevity assurance mechanisms. The expression of multiple detoxification enzymes, each with a significant but relatively modest effect on longevity, is coordinately regulated by signaling pathways such as insulin/insulin-like signaling, explaining the large effect of such pathways on life span. The major aging-related toxicants and their cognate detoxification systems are discussed in this review. PMID:18547875

  1. Radiolabeling in Biology.

    PubMed

    Zhang, Xiaoying; Zhang, Yangde; Malhotra, Anshoo

    2015-05-01

    Chemistry is the science of chemical reactions, the study of chemical properties, composition, and structure of a molecule. When the molecule under observation is of a biological origin (proteins, carbohydrates, lipids, or nucleic acids), the study of its chemical properties, reactions, and structure is known as biochemistry. Similarly, if the molecule or a biochemical under observation is radioactive, the science becomes radiochemistry or radio biochemistry. So, chemistry is the science which fuses these two diverse fields of applied sciences. Fusion of these two sciences on chemistry platform has enabled the development of various new radioactive formulations which are called as radiopharmaceuticals and are being used the world over for clinical as well as experimental purposes. For the successful development of radiopharmaceuticals, we require in-depth understanding of both biochemistry as well as radiochemistry. So, the present review article summarizes basic relevant details and experimental advances in both these sciences with regard to development of radiopharmaceuticals. PMID:25413964

  2. Retrieving relevant experiments: The case of microRNA microarrays.

    PubMed

    Açıcı, Koray; Terzi, Yunus Kasım; Oğul, Hasan

    2015-08-01

    Content-based retrieval of biological experiments in large public repositories is a recent challenge in computational biology and bioinformatics. The task is, in general, to search in a database using a query-by-example without any experimental meta-data annotation. Here, we consider a more specific problem that seeks a solution for retrieving relevant microRNA experiments from microarray repositories. A computational framework is proposed with this objective. The framework adapts a normal-uniform mixture model for identifying differentially expressed microRNAs in microarray profiling experiments. A rank-based thresholding scheme is offered to binarize real-valued experiment fingerprints based on differential expression. An effective similarity metric is introduced to compare categorical fingerprints, which in turn infers the relevance between two experiments. Two different views of experimental relevance are evaluated, one for disease association and another for embryonic germ layer, to discern the retrieval ability of the proposed model. To the best of our knowledge, the experiment retrieval task is investigated for the first time in the context of microRNA microarrays. PMID:26116091

  3. Identifying relevant positions in proteins by Critical Variable Selection.

    PubMed

    Grigolon, Silvia; Franz, Silvio; Marsili, Matteo

    2016-06-21

    Evolution in its course has found a variety of solutions to the same optimisation problem. The advent of high-throughput genomic sequencing has made available extensive data from which, in principle, one can infer the underlying structure on which biological functions rely. In this paper, we present a new method aimed at the extraction of sites encoding structural and functional properties from a set of protein primary sequences, namely a multiple sequence alignment. The method, called critical variable selection, is based on the idea that subsets of relevant sites correspond to subsequences that occur with a particularly broad frequency distribution in the dataset. By applying this algorithm to in silico sequences, to the response regulator receiver and to the voltage sensor domain of ion channels, we show that this procedure recovers not only the information encoded in single site statistics and pairwise correlations but also captures dependencies going beyond pairwise correlations. The method proposed here is complementary to statistical coupling analysis, in that the most relevant sites predicted by the two methods differ markedly. We find robust and consistent results for datasets as small as few hundred sequences that reveal a hidden hierarchy of sites that are consistent with the present knowledge on biologically relevant sites and evolutionary dynamics. This suggests that critical variable selection is capable of identifying a core of sites encoding functional and structural information in a multiple sequence alignment. PMID:26974515

  4. The Personal Relevance of the Social Studies.

    ERIC Educational Resources Information Center

    VanSickle, Ronald L.

    1990-01-01

    Conceptualizes a personal-relevance framework derived from Ronald L. VanSickle's five areas of life integrated with four general motivating goals from Abraham Maslow's hierarchy of needs and Richard and Patricia Schmuck's social motivation theory. Illustrates ways to apply the personal relevance framework to make social studies more relevant to…

  5. Biological membranes

    PubMed Central

    Watson, Helen

    2015-01-01

    Biological membranes allow life as we know it to exist. They form cells and enable separation between the inside and outside of an organism, controlling by means of their selective permeability which substances enter and leave. By allowing gradients of ions to be created across them, membranes also enable living organisms to generate energy. In addition, they control the flow of messages between cells by sending, receiving and processing information in the form of chemical and electrical signals. This essay summarizes the structure and function of membranes and the proteins within them, and describes their role in trafficking and transport, and their involvement in health and disease. Techniques for studying membranes are also discussed. PMID:26504250

  6. Biological Effects of Directed Energy

    NASA Astrophysics Data System (ADS)

    Dayton, Thomas; Beason, Charles; Hitt, M. K.; Rogers, Walter; Cook, Michael

    2002-11-01

    This Final Report summarizes the biological effects research conducted by Veridian Engineering personnel under contract F41624-96-C-9009 in support of the Air Force Research Laboratory's Radio Frequency Radiation Branch from April 1997 to April 2002. Biological effects research and consultation were provided in five major areas: Active Denial System (also known as Vehicle Mounted Active Denial System), radio frequency radiation (RFR) health and safety, non-lethal weapon biological effects research, the newly formed Joint Non-Lethal Weapons Human Effects Center of Excellence, and Biotechnology. The report is organized by research efforts within the major research areas, providing title, objective, a brief description, relevance to the AF or DoD, funding, and products.

  7. NASA Workshop on Biological Adaptation

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily (Editor); Tischler, Marc (Editor)

    1988-01-01

    A workshop was convened to review the current program in Space Biology Biological Adaptation Research and its objectives and to identify future research directions. Two research areas emerged from these deliberations: gravitational effects on structures and biomineralization and gravity affected regulatory mechanisms. The participants also recommended that research concentrate on rapidly growing animals, since gravity effects may be more pronounced during growth and development. Both research areas were defined and future research directions were identified. The recommendations of the workshop will assist the Life Sciences Division of NASA in it assessment and long-range planning of these areas of space biology. Equally important, the workshop was intended to stimulate thought and research among those attending so that they would, in turn, interest, excite, and involve other members of the academic community in research efforts relevant to these programs.

  8. Simple and low cost method for metal-based micro-capillary channels for heat exchanger use

    NASA Astrophysics Data System (ADS)

    Ogbonnaya, E.; Champagne, C.; Weiss, L.

    2013-11-01

    In this work, we present an alternative, low cost method for the fabrication of a heat exchanger utilizing metal-based microchannels using the UV-LiGA technique. Lithography is used to pattern dry film negative photoresist (Ordyl P-50100) on the substrate. The resist is laminated over the substrate and exposed with a UV source. The use of dry film resist allows for simple and inexpensive microchannel patterns without requiring advanced cleanroom equipment. Following the lithography process, electrodeposition of metals is used to fill the recesses patterned in the resist. In this work, nickel has been electroplated into the bounding resist structure. After electroplating, the remaining resist is dissolved leaving free standing metal structures. The fabricated exchanger is then evaluated based on thermal absorption of simulated waste heat sources and capillary action of the metal channels themselves. Channels are fabricated to heights of 60, 70 and 90 μm respectively on copper substrate using these methods. Working fluid mass transfer rate from the heated microchannel heat exchanger (MHE) is utilized as a basic metric of operation. The mass transfer rate recorded from the nickel-based MHE is 2.19, 2.81 and 3.20 mg s-1 respectively for the different channel heights. This implies an effective thermal power consumption rate of 1.66, 2.13 and 2.42 kW m-2 respectively. By contrast, an MHE fabricated with 115 and 142 μm tall channels on silicon substrate is shown to evaporate up to 2.84 and 3.04 mg s-1 respectively, giving an effective thermal power consumption of 2.15 and 2.31 kW m-2 respectively. An investigation of working fluid contact angle with the electroplated nickel surface is also presented. The surface is found to be a porous structure stemming from the electroplating process.

  9. Structural Biology Fact Sheet

    MedlinePlus

    ... Home > Science Education > Structural Biology Fact Sheet Structural Biology Fact Sheet Tagline (Optional) Middle/Main Content Area What is structural biology? Structural biology is a field of science focused ...

  10. Spatial Aspects in Biological System Simulations

    SciTech Connect

    Resat, Haluk; Costa, Michelle N.; Shankaran, Harish

    2011-01-30

    Mathematical models of the dynamical properties of biological systems aim to improve our understanding of the studied system with the ultimate goal of being able to predict system responses in the absence of experimentation. Despite the enormous advances that have been made in biological modeling and simulation, the inherently multiscale character of biological systems and the stochasticity of biological processes continue to present significant computational and conceptual challenges. Biological systems often consist of well-organized structural hierarchies, which inevitably lead to multiscale problems. This chapter introduces and discusses the advantages and shortcomings of several simulation methods that are being used by the scientific community to investigate the spatio-temporal properties of model biological systems. We first describe the foundations of the methods and then describe their relevance and possible application areas with illustrative examples from our own research. Possible ways to address the encountered computational difficulties are also discussed.

  11. Enhancement, disability and the riddle of the relevant circumstances.

    PubMed

    Zohny, Hazem

    2016-09-01

    The welfarist account of enhancement and disability holds enhanced and disabled states on a spectrum: the former are biological or psychological states that increase the chances of a person leading a good life in the relevant set of circumstances, while the latter decrease those chances. Here, I focus on a particular issue raised by this account: what should we count as part of an individual's relevant set of circumstances when thinking about enhanced and disabled states? Specifically, is social prejudice relevant to an individual's circumstances in regards to how disabled or enhanced they are? For instance, if an individual is discriminated against on the basis of their skin colour, and this leads to a reduction in their well-being, the welfarist account suggests that their skin colour is a disability. To avoid such a seeming mislabel, Savulescu and Kahane have argued for excluding social prejudice from counting as a relevant circumstance to their welfarist definition of disability. I argue, however, that this exclusion of social prejudice is unsatisfactory and incompatible with the goals of this account. PMID:27178536

  12. Simulating Biological and Non-Biological Motion

    ERIC Educational Resources Information Center

    Bruzzo, Angela; Gesierich, Benno; Wohlschlager, Andreas

    2008-01-01

    It is widely accepted that the brain processes biological and non-biological movements in distinct neural circuits. Biological motion, in contrast to non-biological motion, refers to active movements of living beings. Aim of our experiment was to investigate the mechanisms underlying mental simulation of these two movement types. Subjects had to…

  13. Biomedically relevant chemical and physical properties of coal combustion products.

    PubMed Central

    Fisher, G L

    1983-01-01

    The evaluation of the potential public and occupational health hazards of developing and existing combustion processes requires a detailed understanding of the physical and chemical properties of effluents available for human and environmental exposures. These processes produce complex mixtures of gases and aerosols which may interact synergistically or antagonistically with biological systems. Because of the physicochemical complexity of the effluents, the biomedically relevant properties of these materials must be carefully assessed. Subsequent to release from combustion sources, environmental interactions further complicate assessment of the toxicity of combustion products. This report provides an overview of the biomedically relevant physical and chemical properties of coal fly ash. Coal fly ash is presented as a model complex mixture for health and safety evaluation of combustion processes. PMID:6337824

  14. Extent of structural asymmetry in homodimeric proteins: prevalence and relevance.

    PubMed

    Swapna, Lakshmipuram Seshadri; Srikeerthana, Kuchi; Srinivasan, Narayanaswamy

    2012-01-01

    Most homodimeric proteins have symmetric structure. Although symmetry is known to confer structural and functional advantage, asymmetric organization is also observed. Using a non-redundant dataset of 223 high-resolution crystal structures of biologically relevant homodimers, we address questions on the prevalence and significance of asymmetry. We used two measures to quantify global and interface asymmetry, and assess the correlation of several molecular and structural parameters with asymmetry. We have identified rare cases (11/223) of biologically relevant homodimers with pronounced global asymmetry. Asymmetry serves as a means to bring about 2:1 binding between the homodimer and another molecule; it also enables cellular signalling arising from asymmetric macromolecular ligands such as DNA. Analysis of these cases reveals two possible mechanisms by which possible infinite array formation is prevented. In case of homodimers associating via non-topologically equivalent surfaces in their tertiary structures, ligand-dependent mechanisms are used. For stable dimers binding via large surfaces, ligand-dependent structural change regulates polymerisation/depolymerisation; for unstable dimers binding via smaller surfaces that are not evolutionarily well conserved, dimerisation occurs only in the presence of the ligand. In case of homodimers associating via interaction surfaces with parts of the surfaces topologically equivalent in the tertiary structures, steric hindrance serves as the preventive mechanism of infinite array. We also find that homodimers exhibiting grossly symmetric organization rarely exhibit either perfect local symmetry or high local asymmetry. Binding of small ligands at the interface does not cause any significant variation in interface asymmetry. However, identification of biologically relevant interface asymmetry in grossly symmetric homodimers is confounded by the presence of similar small magnitude changes caused due to artefacts of

  15. How is physiology relevant to behavior analysis?

    PubMed Central

    Reese, Hayne W.

    1996-01-01

    Physiology is an important biological science; but behavior analysis is not a biological science, and behavior analysts can safely ignore biological processes. However, ignoring products of biological processes might be a serious mistake. The important products include behavior, instinctive drift, behavior potentials, hunger, and many developmental milestones and events. Physiology deals with the sources of such products; behavior analysis can deal with how the products affect behavior, which can be understood without understanding their sources. PMID:22478240

  16. Tuning of the spin distribution between ligand- and metal-based spin: electron paramagnetic resonance of mixed-ligand molybdenum tris(dithiolene) complex anions.

    PubMed

    Fekl, Ulrich; Sarkar, Biprajit; Kaim, Wolfgang; Zimmer-De Iuliis, Marco; Nguyen, Neilson

    2011-09-19

    Electron paramagnetic resonance spectra of homoleptic and mixed-ligand molybdenum tris(dithiolene) complex anions [Mo(tfd)(m)(bdt)(n)](-) (n + m = 3; bdt = S(2)C(6)H(4); tfd = S(2)C(2)(CF(3))(2)) reveal that the spin density has mixed metal-ligand character with more ligand-based spin for [Mo(tfd)(3)](-) and a higher degree of metal-based spin for [Mo(bdt)(3)](-): the magnitude of the isotropic (95,97)Mo hyperfine interaction increases continuously, by a factor of 2.5, on going from the former to the latter. The mixed complexes fall in between, and the metal character of the spin increases with the bdt content. The experiments were corroborated by density functional theory computations, which reproduce this steady increase in metal-based character. PMID:21853970

  17. A facile and high-recovery material for rare-metals based on a water-soluble polyallylamine with side-chain thiourea groups.

    PubMed

    Nagai, Daisuke; Yoshida, Megumi; Kishi, Takuya; Morinaga, Hisatoyo; Hara, Yusuke; Mori, Masanobu; Kawakami, Satoshi; Inoue, Kenji

    2013-08-01

    We describe a facile and high-recovery material for rare metals based on a polymer combining amino groups for water solubility and thiourea groups for metal complexation. Good solubility in aqueous metal ion solutions allows for homogeneous and efficient adsorption by the polymer, and a maximum Pd(II) recovery amount (0.508 gPd gpolymer(-1)) greater than those of other polymers reported in the literature. PMID:23788410

  18. System biology of gene regulation.

    PubMed

    Baitaluk, Michael

    2009-01-01

    A famous joke story that exhibits the traditionally awkward alliance between theory and experiment and showing the differences between experimental biologists and theoretical modelers is when a University sends a biologist, a mathematician, a physicist, and a computer scientist to a walking trip in an attempt to stimulate interdisciplinary research. During a break, they watch a cow in a field nearby and the leader of the group asks, "I wonder how one could decide on the size of a cow?" Since a cow is a biological object, the biologist responded first: "I have seen many cows in this area and know it is a big cow." The mathematician argued, "The true volume is determined by integrating the mathematical function that describes the outer surface of the cow's body." The physicist suggested: "Let's assume the cow is a sphere...." Finally the computer scientist became nervous and said that he didn't bring his computer because there is no Internet connection up there on the hill. In this humorous but explanatory story suggestions proposed by theorists can be taken to reflect the view of many experimental biologists that computer scientists and theorists are too far removed from biological reality and therefore their theories and approaches are not of much immediate usefulness. Conversely, the statement of the biologist mirrors the view of many traditional theoretical and computational scientists that biological experiments are for the most part simply descriptive, lack rigor, and that much of the resulting biological data are of questionable functional relevance. One of the goals of current biology as a multidisciplinary science is to bring people from different scientific areas together on the same "hill" and teach them to speak the same "language." In fact, of course, when presenting their data, most experimentalist biologists do provide an interpretation and explanation for the results, and many theorists/computer scientists aim to answer (or at least to fully describe

  19. [New challenges in the biological weapons convention].

    PubMed

    Sissonen, Susanna; Raijas, Tiina; Haikala, Olli; Hietala, Heikki; Virri, Markku; Nikkari, Simo

    2012-01-01

    Microbes and their toxins are biological weapons that can cause disease in humans, animals or plants, and which can be used with hostile intent in warfare and terrorism. Biological agents can be used as weapons of mass destruction and therefore, immense human and social and major economical damage can be caused. Rapid development of life sciences and technologies during the recent decades has posed new challenges to the Biological Weapons Convention. The Convention states that the States Parties to the BWC strive to ensure that the Convention remains relevant and effective, despite changes in science, technology or politics. PMID:22428382

  20. Planetary Protection: Two Relevant Terrestrial Examples

    NASA Astrophysics Data System (ADS)

    Chyba, C.

    2002-09-01

    Concerns about potential pathogens in returned samples from Mars ("Mars Sample Return: Issues and Recommendations", National Research Council, 1997) or planetary satellites ("Evaluating the Biological Potential in Samples Returned from Planetary Satellites and Small Solar System Bodies", National Research Council, 1998) focus on two potential types of pathogenesis, toxic and infectious. The National Research Council reports cited above state that the chances of extraterrestrial organisms proving either toxic or infectious to humans are extremely low, but cannot be entirely ruled out. Here I discuss recently discovered terrestrial examples relevant to each possibility, in order to make these concerns concrete. The first example concerns the production of hepatotoxins (toxins affecting the liver) and neurotoxins by cyanobacteria in glacial lakes on alpine pastures in Switzerland. In this example, mat-forming benthic cyanobacteria are implicated in a hundred cattle poisonings that have been reported from alpine pasteurs in southeastern Switzerland over the past twenty-five years (e.g. K. Mez et al, Hydrobiologia 368, 1-15 (1998)). It is unlikely that these cyanobacteria evolved the toxins in response to dairy cows; rather the susceptibility of cattle to these toxins seems simply to be an unfortunate coincidence of a toxin working across a large evolutionary distance. The second example concerns the recent demonstration that the decimation of shallow-water Caribbean elkhorn coral is due to infection by a common fecal enterobacterium associated with the human gut (K. L. Patterson et al., PNAS 99, 8725-8730 (2002)). The bacterium, Serratia marcenscens, is also a free-living microbe in water and soil, as well as an opportunistic pathogen in a variety of animal species. The distance between humans and corals emphasizes the possibility that certain organisms may prove pathogenic across a wide evolutionary divide. Of course, in neither of these cases are the evolutionary

  1. A new take on comparative immunology; Relevance to immunotherapy

    PubMed Central

    Wang, Ena; Albini, Adriana; Stroncek, David F; Marincola, Francesco M

    2012-01-01

    Summary It is becoming increasingly recognized that experimental animal models, while useful to address monothematic biological questions, bear unpredictable relevance to human disease. Several reasons have been proposed. However, the uncontrollable nature of human genetics and the heterogeneity of disease that with difficulty can be replicated experimentally play a leading role. Comparative immunology is a term that generally refers to the analysis of shared or diverging facets of immunology among species; these comparisons are carried according to the principle that evolutionarily conserved themes outline biologic functions universally relevant for survival. We propose that a similar strategy could be applied searching for themes shared by distinct immune pathologies within our own species. Identification of common patterns may outline pathways necessary for a particular determinism to occur such as tissue-specific rejection or tolerance. This approach is founded on the unproven but sensible presumption that Nature does not require an infinite plethora of redundant mechanisms to reach its purposes. Thus, immune pathologies must follow, at least in part, common means that determine their onset and maintenance. Commonalities among diseases can, in turn, be segregated from disease-specific patterns uncovering essential mechanisms that may represent universal targets for immunotherapy. PMID:20635956

  2. 12 CFR 508.11 - Relevant considerations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 6 2012-01-01 2012-01-01 false Relevant considerations. 508.11 Section 508.11 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.11 Relevant considerations. (a) In determining...

  3. 12 CFR 108.11 - Relevant considerations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Relevant considerations. 108.11 Section 108.11 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 108.11 Relevant considerations. (a) In determining...

  4. 12 CFR 508.11 - Relevant considerations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Relevant considerations. 508.11 Section 508.11 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.11 Relevant considerations. (a) In determining...

  5. 12 CFR 108.11 - Relevant considerations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Relevant considerations. 108.11 Section 108.11 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 108.11 Relevant considerations. (a) In determining...

  6. 12 CFR 508.11 - Relevant considerations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Relevant considerations. 508.11 Section 508.11 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.11 Relevant considerations. (a) In determining...

  7. 28 CFR 51.57 - Relevant factors.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Relevant factors. 51.57 Section 51.57 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED Determinations by the Attorney General § 51.57 Relevant factors. Among the factors the Attorney...

  8. Culture, Relevance, and Schooling: Exploring Uncommon Ground

    ERIC Educational Resources Information Center

    Scherff, Lisa, Ed.; Spector, Karen, Ed.

    2011-01-01

    In "Culture, Relevance, and Schooling: Exploring Uncommon Ground," Lisa Scherff, Karen Spector, and the contributing authors conceive of culturally relevant and critically minded pedagogies in terms of opening up new spatial, discursive, and/or embodied learning terrains. Readers will traverse multiple landscapes and look into a variety of spaces…

  9. 33 CFR 51.8 - Relevant considerations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Relevant considerations. 51.8 Section 51.8 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PERSONNEL COAST GUARD DISCHARGE REVIEW BOARD § 51.8 Relevant considerations. In determining the equity and propriety...

  10. Freshwater Biological Traits Database (External Review Draft)

    EPA Science Inventory

    This draft report discusses the development of a database of freshwater biological traits. The database combines several existing traits databases into an online format. The database is also augmented with additional traits that are relevant to detecting climate change-related ef...

  11. Engaging General Biology Students with Learning Contracts

    ERIC Educational Resources Information Center

    Litchfield, Brenda; Mata, Juan; Gray, Laura

    2007-01-01

    Students in a general biology class used a learning contract where they selected chapter-relevant activities they could complete through several formats: oral, written, or artistic. The majority of students felt they learned a lot with this method, the process was motivating, and that it should be used in future semesters. (Contains 6 figures.)

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

    PubMed

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

    2016-01-01

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

  13. Evolutionary relevance facilitates visual information processing.

    PubMed

    Jackson, Russell E; Calvillo, Dusti P

    2013-01-01

    Visual search of the environment is a fundamental human behavior that perceptual load affects powerfully. Previously investigated means for overcoming the inhibitions of high perceptual load, however, generalize poorly to real-world human behavior. We hypothesized that humans would process evolutionarily relevant stimuli more efficiently than evolutionarily novel stimuli, and evolutionary relevance would mitigate the repercussions of high perceptual load during visual search. Animacy is a significant component to evolutionary relevance of visual stimuli because perceiving animate entities is time-sensitive in ways that pose significant evolutionary consequences. Participants completing a visual search task located evolutionarily relevant and animate objects fastest and with the least impact of high perceptual load. Evolutionarily novel and inanimate objects were located slowest and with the highest impact of perceptual load. Evolutionary relevance may importantly affect everyday visual information processing. PMID:24184882

  14. Biological nitric oxide signalling: chemistry and terminology

    PubMed Central

    Heinrich, Tassiele A; da Silva, Roberto S; Miranda, Katrina M; Switzer, Christopher H; Wink, David A; Fukuto, Jon M

    2013-01-01

    Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed. PMID:23617570

  15. First evidence for differential and sequential efferent effects of stimulus relevance and goal conduciveness appraisal.

    PubMed

    Aue, Tatjana; Flykt, Anders; Scherer, Klaus R

    2007-03-01

    In the context of a memory task, participants were presented with pictures displaying biological and cultural threat stimuli or neutral stimuli (stimulus relevance manipulation) with superimposed symbols signaling monetary gains or losses (goal conduciveness manipulation). Results for heart rate and facial electromyogram show differential efferent effects of the respective appraisal outcomes and provide first evidence for sequential processing, as postulated by Scherer's component process model of emotion. Specifically, as predicted, muscle activity over the brow and cheek regions marking the process of relevance appraisal occurred significantly earlier than facial muscle activity markers of goal conduciveness appraisal. Heart rate, in contrast, was influenced by the stimulus relevance manipulation only. PMID:17052833

  16. Phobos Sample return and Planetary Protection - Issues of relevance

    NASA Astrophysics Data System (ADS)

    Walter, Nicolas; Worms, Jean-Claude

    This presentation will cover the main issues raised during a dedicated workshop supported by ESA, NASA and COSPAR and hosted by Fraunhofer Institute for High-Speed Dynamics (EMI, Freiburg) in June 2013. The workshop discussed backward planetary protection aspects of the Phootprint Mission concept in the general context of its categorisation. The Phootprint Mission would be aimed at collecting and returning samples from the Martian moon Phobos. Although Phootprint aims at returning samples from Phobos and not Mars, recent findings indicate that Martian material can be transferred to Phobos as ejecta following meteorite impact on Mars surface. In this context, it is important to assess whether a returned Phobos sample may contain active biological system (transferred from Mars) or not. The workshop considered the following issues: - Natural transfer of material from Mars to Phobos Workshop participants discussed the conditions resulting in Mars material being transferred to Phobos and the characteristics of such transfer. - Hypervelocity impact The workshop participant discussed the result of preliminary impact tests performed by Fraunhofer EMI. These tests involved impacting a basaltic projectile into a granular target. The biological inactivation effect of high velocity impact has to be further studied using the appropriate projectiles and targets. - Ionising radiation The effect of ionising radiation on biological systems potentially transferred to Phobos is also an aspect of critical relevance to be considered. During transfer and after impact on Phobos, material transferred will be subject to different ionising radiations conditions, these would need to be further modelled. - Biological model systems It was put forward that several biological model systems (preferably wild type) would have to be selected in order to perform the impact and radiation inactivation tests. ESA is funding a dedicated test activity based on the workshop output to support the

  17. Nanoelectronics Meets Biology

    NASA Astrophysics Data System (ADS)

    Lieber, Charles

    2012-02-01

    Nanoscale materials enable unique opportunities at the interface between the physical and life sciences, and the interface between nanoelectronic devices and biological systems makes possible communication between these two diverse systems at the length scale relevant to biological function. In this presentation, the development of nanowire nanoelectronic devices and their application as powerful tools for the life sciences will be discussed. First, a brief introduction to nanowire nanoelectronic devices as well as comparisons to other electrophysiological tools will be presented to illuminate the unique strengths and opportunities enabled at the nanoscale. Second, illustration of detection capabilities including signal-to-noise and applications for real-time label-free detection of biochemical markers down to the level of single molecules will be described. Third, the use of nanowire nanoelectronics for building interfaces to cells and tissue will be reviewed. Multiplexed measurements made from nanowire devices fabricated on flexible and transparent substrates recording signal propagation across cultured cells, acute tissue slices and intact organs will be illustrated, including quantitative analysis of the high simultaneous spatial and temporal resolution achieved with these nanodevices. Specific examples of subcellular and near point detection of extracellular potential will be used to illustrate the unique capabilities, such as recording localized potential changes due to neuronal activities simultaneously across many length scales, which provide key information for functional neural circuit studies. Last, emerging opportunities for the creation of powerful new probes based on controlled synthesis and/or bottom-up assembly of nanomaterials will be described with an emphasis on nanowire probes demonstrating the first intracellular transistor recordings, and the development of ``cyborg'' tissue. The prospects for blurring the distinction between nanoelectronic

  18. [Functionally-relevant conformational dynamics of water-soluble proteins].

    PubMed

    Novikov, G V; Sivozhelezov, V S; Shaĭtan, K V

    2013-01-01

    A study is reported of the functional-relevant dynamics of three typical water-soluble proteins: Calmodulin, Src-tyrosine kinase as well as repressor of Trp operon. Application of the state-of-art methods of structural bioinformatics allowed to identify dynamics seen in the X-ray structures of the investigated proteins associated with their specific biological functions. In addition, Normal Mode analysis technique revealed the most probable directions of the functionally-relevant motions for all that proteins were also predicted. Importantly, overall type of the motions observed on the lowest-frequency modes was very similar to the motions seen from the analysis of the X-ray data of the examined macromolecules. Thereby it was shown that the large-scale as well as local conformational motions of the proteins might be predetermined already at the level of their tertiary structures. In particular, the determining factor might be the specific fold of the alpha-helixes. Thus functionally-relevant in vivo dynamics of the investigated proteins might be evolutionally formed by means of natural selection at the level of the spatial topology. PMID:23705506

  19. Transforming Big Data into Cancer-Relevant Insight: An Initial, Multi-Tier Approach to Assess Reproducibility and Relevance.

    PubMed

    2016-08-01

    The Cancer Target Discovery and Development (CTD(2)) Network was established to accelerate the transformation of "Big Data" into novel pharmacologic targets, lead compounds, and biomarkers for rapid translation into improved patient outcomes. It rapidly became clear in this collaborative network that a key central issue was to define what constitutes sufficient computational or experimental evidence to support a biologically or clinically relevant finding. This article represents a first attempt to delineate the challenges of supporting and confirming discoveries arising from the systematic analysis of large-scale data resources in a collaborative work environment and to provide a framework that would begin a community discussion to resolve these challenges. The Network implemented a multi-tier framework designed to substantiate the biological and biomedical relevance as well as the reproducibility of data and insights resulting from its collaborative activities. The same approach can be used by the broad scientific community to drive development of novel therapeutic and biomarker strategies for cancer. Mol Cancer Res; 14(8); 675-82. ©2016 AACR. PMID:27401613

  20. Industrial systems biology and its impact on synthetic biology of yeast cell factories.

    PubMed

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc. PMID:26524089

  1. Introducing systems biology for nursing science.

    PubMed

    Founds, Sandra A

    2009-07-01

    Systems biology expands on general systems theory as the "omics'' era rapidly progresses. Although systems biology has been institutionalized as an interdisciplinary framework in the biosciences, it is not yet apparent in nursing. This article introduces systems biology for nursing science by presenting an overview of the theory. This framework for the study of organisms from molecular to environmental levels includes iterations of computational modeling, experimentation, and theory building. Synthesis of complex biological processes as whole systems rather than isolated parts is emphasized. Pros and cons of systems biology are discussed, and relevance of systems biology to nursing is described. Nursing research involving molecular, physiological, or biobehavioral questions may be guided by and contribute to the developing science of systems biology. Nurse scientists can proactively incorporate systems biology into their investigations as a framework for advancing the interdisciplinary science of human health care. Systems biology has the potential to advance the research and practice goals of the National Institute for Nursing Research in the National Institutes of Health Roadmap initiative. PMID:19221104

  2. Systems biology approaches in aging research.

    PubMed

    Chauhan, Anuradha; Liebal, Ulf W; Vera, Julio; Baltrusch, Simone; Junghanß, Christian; Tiedge, Markus; Fuellen, Georg; Wolkenhauer, Olaf; Köhling, Rüdiger

    2015-01-01

    Aging is a systemic process which progressively manifests itself at multiple levels of structural and functional organization from molecular reactions and cell-cell interactions in tissues to the physiology of an entire organ. There is ever increasing data on biomedical relevant network interactions for the aging process at different scales of time and space. To connect the aging process at different structural, temporal and spatial scales, extensive systems biological approaches need to be deployed. Systems biological approaches can not only systematically handle the large-scale datasets (like high-throughput data) and the complexity of interactions (feedback loops, cross talk), but also can delve into nonlinear behaviors exhibited by several biological processes which are beyond intuitive reasoning. Several public-funded agencies have identified the synergistic role of systems biology in aging research. Using one of the notable public-funded programs (GERONTOSYS), we discuss how systems biological approaches are helping the scientists to find new frontiers in aging research. We elaborate on some systems biological approaches deployed in one of the projects of the consortium (ROSage). The systems biology field in aging research is at its infancy. It is open to adapt existing systems biological methodologies from other research fields and devise new aging-specific systems biological methodologies. PMID:25341520

  3. Anion binding in biological systems

    NASA Astrophysics Data System (ADS)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  4. 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.

  5. Sandia programs relevant to microelectronics fabrication

    SciTech Connect

    Picraux, S.T.; Vook, F.L.; Gregory, B.L.

    1987-04-01

    This report was prepared for the Semiconductor Industry and the National Laboratories Workshop held at the National Academy of Sciences, Washington, DC, February 24, 1987. It details the current Sandia program activities relevant to microelectronics fabrication.

  6. Meeting the Challenges of Diversity and Relevance.

    ERIC Educational Resources Information Center

    Schwan-Smith, Margaret; Silver, Edward A.

    1995-01-01

    Discusses the QUASAR Project, which has worked with middle school teachers in disadvantaged communities in order to help increase the relevance of mathematics by making connections between the mathematics taught in school and the lives of students. (16 references) (MKR)

  7. Mother Goose Is Alive and Culturally Relevant.

    ERIC Educational Resources Information Center

    Crawley, Sharon

    1992-01-01

    Asserts that Mother Goose rhymes are culturally relevant. Offers ways in which Mother Goose can be used in the classroom. Discusses activities for language arts, movement, art, music, science, and mathematics instruction. (PRA)

  8. 12 CFR 747.311 - Relevant considerations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... cause to believe that there may be an erosion of public confidence in the integrity, safety, or... specific case, appear relevant to the decision to continue in effect, rescind, terminate, or modify...

  9. A Bridge between Two Cultures: Uncovering the Chemistry Concepts Relevant to the Nursing Clinical Practice

    ERIC Educational Resources Information Center

    Brown, Corina E.; Henry, Melissa L. M.; Barbera, Jack; Hyslop, Richard M.

    2012-01-01

    This study focused on the undergraduate course that covers basic topics in general, organic, and biological (GOB) chemistry at a mid-sized state university in the western United States. The central objective of the research was to identify the main topics of GOB chemistry relevant to the clinical practice of nursing. The collection of data was…

  10. 21 CFR 601.32 - General factors relevant to safety and effectiveness.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false General factors relevant to safety and effectiveness. 601.32 Section 601.32 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Diagnostic Radiopharmaceuticals § 601.32 General factors...

  11. Biological conversion system

    DOEpatents

    Scott, C.D.

    A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

  12. Learning Biology by Designing

    ERIC Educational Resources Information Center

    Janssen, Fred; Waarlo, Arend Jan

    2010-01-01

    According to a century-old tradition in biological thinking, organisms can be considered as being optimally designed. In modern biology this idea still has great heuristic value. In evolutionary biology a so-called design heuristic has been formulated which provides guidance to researchers in the generation of knowledge about biological systems.…

  13. Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; Tropsha, Alexander; Faulon, Jean-Loup; Rintoul, Mark D.

    2009-01-01

    The increasing availability of data related to genes, proteins and their modulation by small molecules, paralleled by the emergence of simulation tools in systems biology, has provided a vast amount of biological information. However, there is a critical need to develop cheminformatics tools that can integrate chemical knowledge with these biological databases, with the goal of creating systems chemical biology. PMID:17637771

  14. Translational environmental biology: cell biology informing conservation.

    PubMed

    Traylor-Knowles, Nikki; Palumbi, Stephen R

    2014-05-01

    Typically, findings from cell biology have been beneficial for preventing human disease. However, translational applications from cell biology can also be applied to conservation efforts, such as protecting coral reefs. Recent efforts to understand the cell biological mechanisms maintaining coral health such as innate immunity and acclimatization have prompted new developments in conservation. Similar to biomedicine, we urge that future efforts should focus on better frameworks for biomarker development to protect coral reefs. PMID:24766840

  15. Synthetic biology: insights into biological computation.

    PubMed

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  16. Quantum Effects in Biological Systems

    NASA Astrophysics Data System (ADS)

    Roy, Sisir

    2014-07-01

    The debates about the trivial and non-trivial effects in biological systems have drawn much attention during the last decade or so. What might these non-trivial sorts of quantum effects be? There is no consensus so far among the physicists and biologists regarding the meaning of "non-trivial quantum effects". However, there is no doubt about the implications of the challenging research into quantum effects relevant to biology such as coherent excitations of biomolecules and photosynthesis, quantum tunneling of protons, van der Waals forces, ultrafast dynamics through conical intersections, and phonon-assisted electron tunneling as the basis for our sense of smell, environment assisted transport of ions and entanglement in ion channels, role of quantum vacuum in consciousness. Several authors have discussed the non-trivial quantum effects and classified them into four broad categories: (a) Quantum life principle; (b) Quantum computing in the brain; (c) Quantum computing in genetics; and (d) Quantum consciousness. First, I will review the above developments. I will then discuss in detail the ion transport in the ion channel and the relevance of quantum theory in brain function. The ion transport in the ion channel plays a key role in information processing by the brain.

  17. Rethinking "relevance": South African psychology in context.

    PubMed

    Long, Wahbie

    2013-02-01

    This article examines the phenomenon known as the "relevance debate" in South African psychology. It begins with a historical overview of the contours of the discipline in that country before describing the controversy's international dimensions, namely, the revolutionary politics of 1960s higher education and the subsequent emergence of cognate versions of the debate in American, European, and "Third World" psychology. The article then details how South Africa's "relevance" project enjoyed a special affinity with an assortment of ethnic-cultural, national, and continental myths and metaphors, all of which served the interests of the political formations of the day. It discusses how, in present-day South Africa, the intelligentsia has become an important catalyst for the so-called African Renaissance, which seeks to provide "relevant" solutions for the regeneration of African society. However, the global hegemony of what began in the 1970s as a "second academic revolution," aided by the lifting of the academic boycott of South Africa, has blunted the once critical edge of "relevance" discourse. A new mode of knowledge production now holds sway, the outcome of a dramatic reformulation of the capitalist manifesto in which the values of the "May 68" generation have been hijacked by a managerialist rationality. In light of the capitalization of the knowledge-production enterprise, it is concluded that the idiom of "relevance" has outlived its usefulness. PMID:23421936

  18. Multiscale Computational Models of Complex Biological Systems

    PubMed Central

    Walpole, Joseph; Papin, Jason A.; Peirce, Shayn M.

    2014-01-01

    Integration of data across spatial, temporal, and functional scales is a primary focus of biomedical engineering efforts. The advent of powerful computing platforms, coupled with quantitative data from high-throughput experimental platforms, has allowed multiscale modeling to expand as a means to more comprehensively investigate biological phenomena in experimentally relevant ways. This review aims to highlight recently published multiscale models of biological systems while using their successes to propose the best practices for future model development. We demonstrate that coupling continuous and discrete systems best captures biological information across spatial scales by selecting modeling techniques that are suited to the task. Further, we suggest how to best leverage these multiscale models to gain insight into biological systems using quantitative, biomedical engineering methods to analyze data in non-intuitive ways. These topics are discussed with a focus on the future of the field, the current challenges encountered, and opportunities yet to be realized. PMID:23642247

  19. Chemical Foundations of Hydrogen Sulfide Biology

    PubMed Central

    Li, Qian; Lancaster, Jack R.

    2013-01-01

    Following nitric oxide (nitrogen monoxide) and carbon monoxide, hydrogen sulfide (or its newer systematic name sulfane, H2S) became the third small molecule that can be both toxic and beneficial depending on the concentration. In spite of its impressive therapeutic potential, the underlying mechanisms for its beneficial effects remain unclear. Any novel mechanism has to obey fundamental chemical principles. H2S chemistry was studied long before its biological relevance was discovered, however, with a few exceptions, these past works have received relatively little attention in the path of exploring the mechanistic conundrum of H2S biological functions. This review calls attention to the basic physical and chemical properties of H2S, focuses on the chemistry between H2S and its three potential biological targets: oxidants, metals and thiol derivatives, discusses the applications of these basics into H2S biology and methodology, and introduces the standard terminology to this youthful field. PMID:23850631

  20. Chemical foundations of hydrogen sulfide biology.

    PubMed

    Li, Qian; Lancaster, Jack R

    2013-11-30

    Following nitric oxide (nitrogen monoxide) and carbon monoxide, hydrogen sulfide (or its newer systematic name sulfane, H2S) became the third small molecule that can be both toxic and beneficial depending on the concentration. In spite of its impressive therapeutic potential, the underlying mechanisms for its beneficial effects remain unclear. Any novel mechanism has to obey fundamental chemical principles. H2S chemistry was studied long before its biological relevance was discovered, however, with a few exceptions, these past works have received relatively little attention in the path of exploring the mechanistic conundrum of H2S biological functions. This review calls attention to the basic physical and chemical properties of H2S, focuses on the chemistry between H2S and its three potential biological targets: oxidants, metals and thiol derivatives, discusses the applications of these basics into H2S biology and methodology, and introduces the standard terminology to this youthful field. PMID:23850631

  1. Computational investigations of HNO in biology

    PubMed Central

    Zhang, Yong

    2013-01-01

    HNO (nitroxyl) has been found to have many physiological effects in numerous biological processes. Computational investigations have been employed to help understand the structural properties of HNO complexes and HNO reactivities in some interesting biologically relevant systems. The following computational aspects were reviewed in this work: 1) structural and energetic properties of HNO isomers; 2) interactions between HNO and non-metal molecules; 3) structural and spectroscopic properties of HNO metal complexes; 4) HNO reactions with biologically important non-metal systems; 5) involvement of HNO in reactions of metal complexes and metalloproteins. Results indicate that computational investigations are very helpful to elucidate interesting experimental phenomena and provide new insights into unique structural, spectroscopic, and mechanistic properties of HNO involvement in biology. PMID:23103077

  2. Relevance and Significance of Extraterrestrial Abiological Hydrocarbon Chemistry.

    PubMed

    Olah, George A; Mathew, Thomas; Prakash, G K Surya

    2016-06-01

    Astrophysical observations show similarity of observed abiological "organics"-i.e., hydrocarbons, their derivatives, and ions (carbocations and carbanions)-with studied terrestrial chemistry. Their formation pathways, their related extraterrestrial hydrocarbon chemistry originating from carbon and other elements after the Big Bang, their parent hydrocarbon and derivative (methane and methanol, respectively), and transportation of derived building blocks of life by meteorites or comets to planet Earth are discussed in this Perspective. Their subsequent evolution on Earth under favorable "Goldilocks" conditions led to more complex molecules and biological systems, and eventually to humans. The relevance and significance of extraterrestrial hydrocarbon chemistry to the limits of science in relation to the physical aspects of evolution on our planet Earth are also discussed. PMID:27045758

  3. LA-ICP-MS imaging in multicellular tumor spheroids - a novel tool in the preclinical development of metal-based anticancer drugs.

    PubMed

    Theiner, Sarah; Schreiber-Brynzak, Ekaterina; Jakupec, Michael A; Galanski, Markus; Koellensperger, Gunda; Keppler, Bernhard K

    2016-04-01

    A novel application of advanced elemental imaging offers cutting edge in vitro assays with more predictive power on the efficacy of anticancer drugs in preclinical development compared to two dimensional cell culture models. We propose LA-ICP-MS analysis of multicellular spheroids, which are increasingly being used as three dimensional (3D) models of tumors, for improving the in vitro evaluation of anticancer metallodrugs. The presented strategy is very well suited for screening drug-tumor penetration, a key issue for drug efficacy. A major advantage of tumor spheroid models is that they enable us to create a tissue-like structure and function. With respect to 2D culture on the one hand and in vivo models on the other, multicellular spheroids thus show intermediate complexity, still allowing high repeatability and adequate through-put for drug research. This strongly argues for the use of spheroids as bridging models in preclinical anticancer drug development. Probing the lateral platinum distribution within these tumor models allows visualizing the penetration depth and targeting of platinum-based complexes. In the present study, we show for the first time that spatially-resolved metal accumulation in tumor spheroids upon treatment with platinum compounds can be appropriately assessed. The optimized LA-ICP-MS setup allowed discerning the platinum localization in different regions of the tumor spheroids upon compound treatment at biologically relevant (low micromolar) concentrations. Predominant platinum accumulation was observed at the periphery as well as in the center of the spheroids. This corresponds to the proliferating outermost layers of cells and the necrotic core, respectively, indicating enhanced platinum sequestration in these regions. PMID:26806253

  4. Bioavailability and bioaccumulation of metal-based engineered nanomaterials in aquatic environments: concepts and processes: chapter 5

    USGS Publications Warehouse

    Luoma, Samuel N.; Khan, Farhan R.; Croteau, Marie-Noële

    2014-01-01

    Bioavailability of Me-ENMs to aquatic organisms links their release into the environment to ecological implications. Close examination shows some important differences in the conceptual models that define bioavailability for metals and Me-ENMs. Metals are delivered to aquatic animals from Me-ENMs via water, ingestion, and incidental surface exposure. Both metal released from the Me-ENM and uptake of the nanoparticle itself contribute to bioaccumulation. Some mechanisms of toxicity and some of the metrics describing exposure may differ from metals alone. Bioavailability is driven by complex interaction of particle attributes, environmental transformations, and biological traits. Characterization of Me-ENMs is an essential part of understanding bioavailability and requires novel methodologies. The relative importance of the array of processes that could affect Me-ENM bioavailability remains poorly known, but new approaches and models are developing rapidly. Enough is known, however, to conclude that traditional approaches to exposure assessment for metals would not be adequate to assess risks from Me-ENMs.

  5. New metal based drug as a therapeutic agent: Spectral, electrochemical, DNA-binding, surface morphology and photoluminescence properties

    NASA Astrophysics Data System (ADS)

    Muslu, Harun; Gölcü, Ayşegül

    2015-07-01

    Cu(II) complexes of non-steroidal anti-inflammatory drug (NSAID) Meloxicam (H2MLX) was synthesized and characterized via spectroscopic and analytical techniques. The thermal behavior of the complex was also analyzed. The photoluminescence properties of the compounds were analyzed under different conditions. The electrochemical properties of both ligand and complex have been analyzed by Cyclic Voltammetry (CV) using glassy carbon electrode. The biological activities of the compounds were evaluated through examining their capacity to bind to fish sperm double strand DNA (FSdsDNA) with absorption spectroscopy and differential pulse voltammetry (DPV). Absorption studies of the interaction of the H2MLX and its Cu(II) complex with FSdsDNA have indicated that these compounds could bind to FSdsDNA, and the binding constants were calculated. The morphology of the FSdsDNA, H2MLX, and Cu(II) complex were analyzed thanks to using scanning electron microscopy (SEM). In the DPV technique, pencil graphite electrode was used as a working electrode. The decrease in the intensity of the guanine oxidation signals was used as an indicator for the interaction mechanism.

  6. Ask not what physics can do for biology--ask what biology can do for physics.

    PubMed

    Frauenfelder, Hans

    2014-01-01

    Stan Ulam, the famous mathematician, said once to Hans Frauenfelder: 'Ask not what Physics can do for biology, ask what biology can do for physics'. The interaction between biologists and physicists is a two-way street. Biology reveals the secrets of complex systems, physics provides the physical tools and the theoretical concepts to understand the complexity. The perspective gives a personal view of the path to some of the physical concepts that are relevant for biology and physics (Frauenfelder et al 1999 Rev. Mod. Phys. 71 S419-S442). Schrödinger's book (Schrödinger 1944 What is Life? (Cambridge: Cambridge University Press)), loved by physicists and hated by eminent biologists (Dronamraju 1999 Genetics 153 1071-6), still shows how a great physicist looked at biology well before the first protein structure was known. PMID:25292354

  7. Is Biology Boring? Student Attitudes toward Biology

    ERIC Educational Resources Information Center

    Prokop, Pavol; Prokop, Matel; Tunnicliffe, Sue Dale

    2007-01-01

    The study examines the interests and attitudes of school students toward biology: through their interest in out-of-school activities and their attitude towards lessons as measured by interest, importance and difficulty. Biology lessons were relatively popular with the greatest preference found among students learning zoology. Girls showed…

  8. Transforming Big Data into cancer-relevant insight: An initial, multi-tier approach to assess reproducibility and relevance | Office of Cancer Genomics

    Cancer.gov

    The Cancer Target Discovery and Development (CTD^2) Network was established to accelerate the transformation of "Big Data" into novel pharmacological targets, lead compounds, and biomarkers for rapid translation into improved patient outcomes. It rapidly became clear in this collaborative network that a key central issue was to define what constitutes sufficient computational or experimental evidence to support a biologically or clinically relevant finding.

  9. Passage relevance models for genomics search

    PubMed Central

    Urbain, Jay; Frieder, Ophir; Goharian, Nazli

    2009-01-01

    We present a passage relevance model for integrating syntactic and semantic evidence of biomedical concepts and topics using a probabilistic graphical model. Component models of topics, concepts, terms, and document are represented as potential functions within a Markov Random Field. The probability of a passage being relevant to a biologist's information need is represented as the joint distribution across all potential functions. Relevance model feedback of top ranked passages is used to improve distributional estimates of query concepts and topics in context, and a dimensional indexing strategy is used for efficient aggregation of concept and term statistics. By integrating multiple sources of evidence including dependencies between topics, concepts, and terms, we seek to improve genomics literature passage retrieval precision. Using this model, we are able to demonstrate statistically significant improvements in retrieval precision using a large genomics literature corpus. PMID:19344479

  10. Quantum metrology and its application in biology

    NASA Astrophysics Data System (ADS)

    Taylor, Michael A.; Bowen, Warwick P.

    2016-02-01

    Quantum metrology provides a route to overcome practical limits in sensing devices. It holds particular relevance to biology, where sensitivity and resolution constraints restrict applications both in fundamental biophysics and in medicine. Here, we review quantum metrology from this biological context, focusing on optical techniques due to their particular relevance for biological imaging, sensing, and stimulation. Our understanding of quantum mechanics has already enabled important applications in biology, including positron emission tomography (PET) with entangled photons, magnetic resonance imaging (MRI) using nuclear magnetic resonance, and bio-magnetic imaging with superconducting quantum interference devices (SQUIDs). In quantum metrology an even greater range of applications arise from the ability to not just understand, but to engineer, coherence and correlations at the quantum level. In the past few years, quite dramatic progress has been seen in applying these ideas into biological systems. Capabilities that have been demonstrated include enhanced sensitivity and resolution, immunity to imaging artefacts and technical noise, and characterization of the biological response to light at the single-photon level. New quantum measurement techniques offer even greater promise, raising the prospect for improved multi-photon microscopy and magnetic imaging, among many other possible applications. Realization of this potential will require cross-disciplinary input from researchers in both biology and quantum physics. In this review we seek to communicate the developments of quantum metrology in a way that is accessible to biologists and biophysicists, while providing sufficient details to allow the interested reader to obtain a solid understanding of the field. We further seek to introduce quantum physicists to some of the central challenges of optical measurements in biological science. We hope that this will aid in bridging the communication gap that exists

  11. Models for synthetic biology

    PubMed Central

    Kaznessis, Yiannis N

    2007-01-01

    Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal. PMID:17986347

  12. Biological information specialists for biological informatics

    PubMed Central

    Heidorn, P Bryan; Palmer, Carole L; Wright, Dan

    2007-01-01

    Data management and integration are complicated and ongoing problems that will require commitment of resources and expertise from the various biological science communities. Primary components of successful cross-scale integration are smooth information management and migration from one context to another. We call for a broadening of the definition of bioinformatics and bioinformatics training to span biological disciplines and biological scales. Training programs are needed that educate a new kind of informatics professional, Biological Information Specialists, to work in collaboration with various discipline-specific research personnel. Biological Information Specialists are an extension of the informationist movement that began within library and information science (LIS) over 30 years ago as a professional position to fill a gap in clinical medicine. These professionals will help advance science by improving access to scientific information and by freeing scientists who are not interested in data management to concentrate on their science. PMID:17295920

  13. Unraveling pancreatic islet biology by quantitative proteomics

    SciTech Connect

    Zhou, Jianying; Dann, Geoffrey P.; Liew, Chong W.; Smith, Richard D.; Kulkarni, Rohit N.; Qian, Weijun

    2011-08-01

    The pancreatic islets of Langerhans play a critical role in maintaining blood glucose homeostasis by secreting insulin and several other important peptide hormones. Impaired insulin secretion due to islet dysfunction is linked to the pathogenesis underlying both Type 1 and Type 2 diabetes. Over the past 5 years, emerging proteomic technologies have been applied to dissect the signaling pathways that regulate islet functions and gain an understanding of the mechanisms of islet dysfunction relevant to diabetes. Herein, we briefly review some of the recent quantitative proteomic studies involving pancreatic islets geared towards gaining a better understanding of islet biology relevant to metabolic diseases.

  14. Classifying Measures of Biological Variation

    PubMed Central

    Gregorius, Hans-Rolf; Gillet, Elizabeth M.

    2015-01-01

    Biological variation is commonly measured at two basic levels: variation within individual communities, and the distribution of variation over communities or within a metacommunity. We develop a classification for the measurement of biological variation on both levels: Within communities into the categories of dispersion and diversity, and within metacommunities into the categories of compositional differentiation and partitioning of variation. There are essentially two approaches to characterizing the distribution of trait variation over communities in that individuals with the same trait state or type tend to occur in the same community (describes differentiation tendencies), and individuals with different types tend to occur in different communities (describes apportionment tendencies). Both approaches can be viewed from the dual perspectives of trait variation distributed over communities (CT perspective) and community membership distributed over trait states (TC perspective). This classification covers most of the relevant descriptors (qualified measures) of biological variation, as is demonstrated with the help of major families of descriptors. Moreover, the classification is shown to open ways to develop new descriptors that meet current needs. Yet the classification also reveals the misclassification of some prominent and widely applied descriptors: Dispersion is often misclassified as diversity, particularly in cases where dispersion descriptor allow for the computation of effective numbers; the descriptor GST of population genetics is commonly misclassified as compositional differentiation and confused with partitioning-oriented differentiation, whereas it actually measures partitioning-oriented apportionment; descriptors of β-diversity are ambiguous about the differentiation effects they are supposed to represent and therefore require conceptual reconsideration. PMID:25807558

  15. [Cross reactivity of food allergens and its clinical relevance].

    PubMed

    Moneret-Vautrin, Denise Anne

    2005-10-01

    Cross-reactions between food allergens and other allergens are a major focus of interest. They include cross-allergies between Betulaceae and Compositae pollen, and also between fruits and vegetables (Prunoideae and Apiaceae). Cross-allergies between animal allergens include mites, cockroaches and crustaceans, milk and meat, animal epithelia, meat and egg. Cross-reactivity results from homology between protein sequences, and is highly likely when this homology reaches about 70%. Phylogenetically similar proteins occur in all species and are known as pan allergens. Profilins, Bet v1 homologues, and lipid transfer proteins have varying degrees of clinical relevance. The involvement of cross-reactivity in the persistence of sensitization and in allergic disorders is unclear. The consequences of cross-reactivity during specific immunotherapy with total allergenic extracts are random. Interpretation of biological tests of IgE binding is also biased by cross-reactivity. The use of panels of major recombinant allergens should help to identify specific sensitization profiles as well as clinically relevant sensitization. Cross-reactivity between epitopes of inhalants and of food allergens may perpetuate and intensify allergic disorders. The consequences of cross-reactivity between allergens and autologous proteins are unknown. PMID:16669147

  16. Real time and label free profiling of clinically relevant exosomes.

    PubMed

    Sina, Abu Ali Ibn; Vaidyanathan, Ramanathan; Dey, Shuvashis; Carrascosa, Laura G; Shiddiky, Muhammad J A; Trau, Matt

    2016-01-01

    Tumor-derived exosomes possess significant clinical relevance due to their unique composition of genetic and protein material that is representative of the parent tumor. Specific isolation as well as identification of proportions of these clinically relevant exosomes (CREs) from biological samples could help to better understand their clinical significance as cancer biomarkers. Herein, we present a simple approach for quantification of the proportion of CREs within the bulk exosome population isolated from patient serum. This proportion of CREs can potentially inform on the disease stage and enable non-invasive monitoring of inter-individual variations in tumor-receptor expression levels. Our approach utilises a Surface Plasmon Resonance (SPR) platform to quantify the proportion of CREs in a two-step strategy that involves (i) initial isolation of bulk exosome population using tetraspanin biomarkers (i.e., CD9, CD63), and (ii) subsequent detection of CREs within the captured bulk exosomes using tumor-specific markers (e.g., human epidermal growth factor receptor 2 (HER2)). We demonstrate the isolation of bulk exosome population and detection of as low as 10% HER2(+) exosomes from samples containing designated proportions of HER2(+) BT474 and HER2(-) MDA-MB-231 cell derived exosomes. We also demonstrate the successful isolation of exosomes from a small cohort of breast cancer patient samples and identified that approximately 14-35% of their bulk population express HER2. PMID:27464736

  17. Real time and label free profiling of clinically relevant exosomes

    PubMed Central

    Sina, Abu Ali Ibn; Vaidyanathan, Ramanathan; Dey, Shuvashis; Carrascosa, Laura G.; Shiddiky, Muhammad J. A.; Trau, Matt

    2016-01-01

    Tumor-derived exosomes possess significant clinical relevance due to their unique composition of genetic and protein material that is representative of the parent tumor. Specific isolation as well as identification of proportions of these clinically relevant exosomes (CREs) from biological samples could help to better understand their clinical significance as cancer biomarkers. Herein, we present a simple approach for quantification of the proportion of CREs within the bulk exosome population isolated from patient serum. This proportion of CREs can potentially inform on the disease stage and enable non-invasive monitoring of inter-individual variations in tumor-receptor expression levels. Our approach utilises a Surface Plasmon Resonance (SPR) platform to quantify the proportion of CREs in a two-step strategy that involves (i) initial isolation of bulk exosome population using tetraspanin biomarkers (i.e., CD9, CD63), and (ii) subsequent detection of CREs within the captured bulk exosomes using tumor-specific markers (e.g., human epidermal growth factor receptor 2 (HER2)). We demonstrate the isolation of bulk exosome population and detection of as low as 10% HER2(+) exosomes from samples containing designated proportions of HER2(+) BT474 and HER2(−) MDA-MB-231 cell derived exosomes. We also demonstrate the successful isolation of exosomes from a small cohort of breast cancer patient samples and identified that approximately 14–35% of their bulk population express HER2. PMID:27464736

  18. Biological monitoring of nickel

    SciTech Connect

    Sunderman, F.W. Jr.; Aitio, A.; Morgan, L.G.; Norseth, T.

    1986-07-01

    Measurements of nickel in body fluids, excreta, and tissues from humans with occupational, environmental, and iatrogenic exposures to nickel compounds are comprehensively reviewed. Correlations between levels of human exposures to various classes of nickel compounds via inhalation, oral, or parenteral routes and the corresponding concentrations of nickel in biological samples are critically evaluated. Major conclusions include the following points: Measurements of nickel concentrations in body fluids, especially urine and serum, provide meaningful insights into the extent of nickel exposures, provided these data are interpreted with knowledge of the exposure routes, sources, and durations, the chemical identities and physical-chemical properties of the nickel compounds, and relevant clinical and physiological information, such as renal function. Nickel concentrations in body fluids should not be viewed as indicators of specific health risks, except in persons exposed to nickel carbonyl, for whom urine nickel concentrations provide prognostic guidance on the severity of the poisoning. In persons exposed to soluble nickel compounds (e.g., NiCl/sub 2/, NiSO/sub 4/), nickel concentrations in body fluids are generally proportional to exposure levels; absence of increased values usually indicates non-significant exposure; presence of increased values should be a signal to reduce the exposure. In persons exposed to less soluble nickel compounds (e.g., Ni/sub 3/S/sub 2/,NiO), increased concentrations of nickel in body fluids are indicative of significant nickel absorption and should be a signal to reduce the exposures to the lowest levels attainable with available technology; absence of increased values does not necessarily indicate freedom from the health risks (e.g., cancers of lung and nasal cavities) associated with exposures to certain relatively insoluble nickel compounds. 315 references.

  19. Engineering biological systems with synthetic RNA molecules

    PubMed Central

    Liang, Joe C.; Bloom, Ryan J.; Smolke, Christina D.

    2011-01-01

    RNA molecules play diverse functional roles in natural biological systems. There has been growing interest in designing synthetic RNA counterparts for programming biological function. The design of synthetic RNA molecules that exhibit diverse activities, including sensing, regulatory, information processing, and scaffolding activities, has highlighted the advantages of RNA as a programmable design substrate. Recent advances in implementing these engineered RNA molecules as key control elements in synthetic genetic networks are highlighting the functional relevance of this class of synthetic elements in programming cellular behaviors. PMID:21925380

  20. Biological treatment and ozone oxidation: Integration or coupling?

    PubMed

    Di Iaconi, Claudio

    2012-02-01

    Wastewaters generated by many economically relevant industrial activities contain recalcitrant organic compounds which pass unaltered through biological stage of the treatment plant making it difficult to meet the discharge limits currently in force. Therefore, an additional treatment is usually required to remove these compounds. In this study, the application of ozonation together with biological treatment was investigated. In particular, the effectiveness of biological degradation followed by or integrated with ozonation for treating the effluents produced by three environmentally relevant activities (i.e., leather and textile processing and municipal waste landfilling) are compared in the present paper. The results show that biological treatment followed by ozonation does not guarantee depurative levels sufficient for discharge for landfill leachates and tannery wastewater. On the contrary, thanks to the synergy between biological degradation and ozonation, integrated treatment significantly improves the process performance for all the investigated wastewaters, thus allowing the discharge limits to be met. PMID:22206914

  1. Using cancer to make cellular reproduction rigorous and relevant

    NASA Astrophysics Data System (ADS)

    Duncan, Cynthia F.

    The 1983 report Nation at Risk highlighted the fact that test scores of American students were far below that of competing nations and educational standards were being lowered. This trend has continued and studies have also shown that students are not entering college ready for success. This trend can be reversed. Students can better understand and retain biology content expectations if they are taught in a way that is both rigorous and relevant. In the past, students have learned the details of cellular reproduction with little knowledge of why it is important to their everyday lives. This material is learned only for the test. Knowing the details of cellular reproduction is crucial for understanding cancer. Cancer is a topic that will likely affect all of my students at some point in their lives. Students used hands on activities, including simulations, labs, and models to learn about cellular reproduction with cancer as a theme throughout. Students were challenged to learn how to use the rigorous biology content expectations to think about cancer, including stem cell research. Students that will some day be college students, voting citizens, and parents, will become better learners. Students were assessed before and after the completion of the unit to determine if learning occurs. Students did learn the material and became more critical thinkers. Statistical analysis was completed to insure confidence in the results.

  2. The emerging role of pharmacogenomics in biologics.

    PubMed

    Lacaná, E; Amur, S; Mummanneni, P; Zhao, H; Frueh, F W

    2007-10-01

    Biologics can be seen as "designer" drugs whose mode of action in a specific disease mechanism is frequently well understood, making it often possible to predict better efficacy and safety profiles for biologics when compared with small molecule drugs. Biologics have been approved for the treatment of major disease classes, such as inflammatory disease, cardiovascular disease, and cancer. However, as it is true for small molecule drugs, often only a fraction of the treated population responds to biologics, and clinical markers for prediction of efficacy are seldom available. It is reasonable to expect that the use of genetic or genomic markers will contribute to improving the prediction of safety and efficacy of both biologics and small molecule drugs. In this paper, we will review the differences between biologics and small molecule drugs, focusing on studies highlighting the relevance of genetic and genomic information on safety and efficacy issues in therapies with biologics. The potential impact of these studies on the promotion of personalized medicine and on regulatory decisions will also be discussed. PMID:17713469

  3. RDFScape: Semantic Web meets Systems Biology

    PubMed Central

    Splendiani, Andrea

    2008-01-01

    Background The recent availability of high-throughput data in molecular biology has increased the need for a formal representation of this knowledge domain. New ontologies are being developed to formalize knowledge, e.g. about the functions of proteins. As the Semantic Web is being introduced into the Life Sciences, the basis for a distributed knowledge-base that can foster biological data analysis is laid. However, there still is a dichotomy, in tools and methodologies, between the use of ontologies in biological investigation, that is, in relation to experimental observations, and their use as a knowledge-base. Results RDFScape is a plugin that has been developed to extend a software oriented to biological analysis with support for reasoning on ontologies in the semantic web framework. We show with this plugin how the use of ontological knowledge in biological analysis can be extended through the use of inference. In particular, we present two examples relative to ontologies representing biological pathways: we demonstrate how these can be abstracted and visualized as interaction networks, and how reasoning on causal dependencies within elements of pathways can be implemented. Conclusions The use of ontologies for the interpretation of high-throughput biological data can be improved through the use of inference. This allows the use of ontologies not only as annotations, but as a knowledge-base from which new information relevant for specific analysis can be derived. PMID:18460179

  4. Culturally Relevant Pedagogy: Clashes and Confrontations

    ERIC Educational Resources Information Center

    Scherff, Lisa, Ed.; Spector, Karen, Ed.

    2010-01-01

    The authors in this edited volume reflect on their experiences with culturally relevant pedagogy--as students, as teachers, as researchers--and how these experiences were often at odds with their backgrounds and/or expectations. Each of the authors speaks to the complexity and difficulty in attempting to address students' cultures, create learning…

  5. The Relevance Aura of Bibliographic Records.

    ERIC Educational Resources Information Center

    Brooks, Terrence A.

    1997-01-01

    Analyzes relevance assessments of topical descriptors for bibliographic records for two dimensions: (1) a vertical conceptual hierarchy of broad to narrow descriptors, and (2) a horizontal linkage of related terms. The data were analyzed for a semantic distance and semantic direction effect as postulated by the Semantic Distance Model. (Author/LRW)

  6. Basic Structure of Work-Relevant Abilities.

    ERIC Educational Resources Information Center

    Prediger, Dale J.

    This study sought to determine whether the dimensions underlying a comprehensive set of 15 work-relevant abilities were similar to the Data/Ideas and Things/People Work Task Dimensions (D. J. Prediger, 1996) underlying J. L. Holland's (1997) hexagonal model of interest and occupational types. The work task dimensions and a general ability…

  7. Making Introductory Cultural Geography More Relevant.

    ERIC Educational Resources Information Center

    Rugg, Dean S.

    1991-01-01

    Presents a project making an introductory class in cultural geography more relevant. Describes how students select and evaluate three articles about geography and write about them. Suggests that students are better able to appreciate and retain a geographical perspective in a comparative world context by applying concepts of their choice to real…

  8. Making Chemistry Relevant to the Engineering Major

    ERIC Educational Resources Information Center

    Basu-Dutt, Sharmistha; Slappey, Charles; Bartley, Julie K.

    2010-01-01

    As part of a campus-wide, externally funded project to increase performance in, enthusiasm for, and retention within STEM disciplines, we developed an interdisciplinary, team-taught first-year seminar course. The construction and delivery of this course was designed to show the relevance of selected general chemistry topics such as matter and…

  9. Clinical Relevance of Nontuberculous Mycobacteria, Oman

    PubMed Central

    Al-Mahruqi, Sara H.; Al-Busaidy, Suleiman; Boeree, Martin J.; Al-Zadjali, Samiya; Patel, Arti; Dekhuijzen, P.N. Richard; van Soolingen, Dick

    2009-01-01

    Little is known about the clinical relevance of nontuberculous mycobacteria (NTM) in the Arabian Peninsula. We assessed the prevalence and studied a random sample of isolates at a reference laboratory in Muscat, Oman. NTM cause disease in this region, and their prevalence has increased. PMID:19193276

  10. Seeking Relevance: American Political Science and America

    ERIC Educational Resources Information Center

    Maranto, Robert; Woessner, Matthew C.

    2012-01-01

    In this article, the authors talk about the relevance of American political science and America. Political science has enormous strengths in its highly talented practitioners and sophisticated methods. However, its disconnection from its host society, while not so severe as for fields like English and sociology, nonetheless poses an existential…

  11. The Relevance of Cosmopolitanism for Moral Education

    ERIC Educational Resources Information Center

    Merry, Michael S.; de Ruyter, Doret J.

    2011-01-01

    In this article we defend a moral conception of cosmopolitanism and its relevance for moral education. Our moral conception of cosmopolitanism presumes that persons possess an inherent dignity in the Kantian sense and therefore they should be recognised as ends-in-themselves. We argue that cosmopolitan ideals can inspire moral educators to awaken…

  12. COMPARING ENVIRONMENTALLY RELEVANT PCBS TO TCDD

    EPA Science Inventory

    COMPARING ENVIRONMENTALLY RELEVANT PCBS TO TCDD. D E Burgin1, J J Diliberto2 and L S Birnbaum3.1UNC, Chapel Hill, NC, USA; 2USEPA/ORD/NHEERL, ETD, RTP, NC, USA

    Environmental exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) always occur as part of a complex mixture. ...

  13. Contingent Attentional Capture by Conceptually Relevant Images

    ERIC Educational Resources Information Center

    Wyble, Brad; Folk, Charles; Potter, Mary C.

    2013-01-01

    Attentional capture is an unintentional shift of visuospatial attention to the location of a distractor that is either highly salient, or relevant to the current task set. The latter situation is referred to as contingent capture, in that the effect is contingent on a match between characteristics of the stimuli and the task-defined…

  14. Is Enterprise Education Relevant to Social Enterprise?

    ERIC Educational Resources Information Center

    Bridge, Simon

    2015-01-01

    Purpose: Both enterprise education and social enterprise have become fashionable but what, if any, should be the connections between them? The purpose of this paper is to explore those connections and to reflect on what relevance the two concepts might have for each other. Design/methodology/approach: Both enterprise education and social…

  15. Culturally Relevant Science Teaching in Middle School

    ERIC Educational Resources Information Center

    Laughter, Judson C.; Adams, Amelia D.

    2012-01-01

    To respond to calls for more research on culturally relevant science teaching, we present findings from one middle school science teacher's practices in an effort to contribute to this research. We describe how a discussion lab centered on Derrick Bell's (1992) short story "The Space Traders" was purposively included in a lesson on scientific bias…

  16. Achieving Relevance in Assessment through Fieldtrips

    ERIC Educational Resources Information Center

    Sutton-Brady, Catherine

    2008-01-01

    Students often bemoan the fact that they can't see the relevance of the report they are asked to write or the case study they have to analyze. This paper introduces the use of attending an industry tradeshow as a means of making assessment more interesting and meaningful. Much has been written about the need to bring reality back to management…

  17. Relevance of microelectronic education to industrial needs

    NASA Technical Reports Server (NTRS)

    Prince, J. L.; Lathrop, J. W.

    1977-01-01

    The relevance of microelectronic education to industrial needs was evaluated, and four categories were surveyed: (1) facts and rules; (2) skills; (3) personality; and (4) deductive-inductive reasoning. Examples of specific items in each category are given to illustrate their meaning and it was indicated as to which items in each category are strongly impacted by microelectronics courses and laboratories.

  18. Advances in Biological Science.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.; And Others

    1988-01-01

    Reviews major developments in areas that are at the cutting edge of biological research. Areas include: human anti-cancer gene, recombinant DNA techniques for the detection of Huntington disease carriers, and marine biology. (CW)

  19. Biological Therapies for Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  20. Biology of Blood

    MedlinePlus

    ... Mail Facebook TwitterTitle Google+ LinkedIn Home Blood Disorders Biology of Blood Overview of Blood Resources In This ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  1. Resetting Biological Clocks

    ERIC Educational Resources Information Center

    Winfree, Arthur T.

    1975-01-01

    Reports on experiments conducted on two biological clocks, in organisms in the plant and animal kingdoms, which indicate that biological oscillation can be arrested by a single stimulus of a definite strength delivered at the proper time. (GS)

  2. Biology Today: Questions & Variations.

    ERIC Educational Resources Information Center

    Flannery, Maura, Ed.

    1988-01-01

    Discusses the importance of student questions as tools of instruction and as indicators of student misconceptions. Suggests different ways in which students may gain an understanding of biological concepts through discussion of popular movies and biological problems. (CW)

  3. Plant metabolomics: from holistic data to relevant biomarkers.

    PubMed

    Wolfender, Jean-Luc; Rudaz, Serge; Choi, Young Hae; Kim, Hye Kyong

    2013-01-01

    Metabolomics is playing an increasingly important role in plant science. It aims at the comprehensive analysis of the plant metabolome which consists both of primary and secondary metabolites. The goal of metabolomics is ultimately to identify and quantify this wide array of small molecules in biological samples. This new science is included in several systems biology approaches and is based primarily on the unbiased acquisition of mass spectrometric (MS) or nuclear magnetic resonance (NMR) data from carefully selected samples. This approach provides the most ''functional'' information of the 'omics' technologies of a given organism since metabolites are the end products of the cellular regulatory processes. The application of state-of-the-art data mining, that includes various untargeted and targeted multivariate data analysis methods, to the vast amount of data generated by this data-driven approach leads to sample classification and the identification of relevant biomarkers. The biological areas that have been successfully studied by this holistic approach include global metabolite composition assessment, mutant and phenotype characterisation, taxonomy, developmental processes, stress response, interaction with the environment, quality control assessment, lead finding and mode of action of botanicals. This review summarises the main MS- and NMR-based approaches that are used to perform these studies and discusses the potential and current limitations of the various methods. The intent is not to provide an exhaustive overview of the field, which has grown considerably over the past decade, but to summarise the main strategies that are used and to discuss the potential and limitations of the different approaches as well as future trends. PMID:23210790

  4. Teaching Biology through Statistics: Application of Statistical Methods in Genetics and Zoology Courses

    ERIC Educational Resources Information Center

    Colon-Berlingeri, Migdalisel; Burrowes, Patricia A.

    2011-01-01

    Incorporation of mathematics into biology curricula is critical to underscore for undergraduate students the relevance of mathematics to most fields of biology and the usefulness of developing quantitative process skills demanded in modern biology. At our institution, we have made significant changes to better integrate mathematics into the…

  5. Monte Carlo simulation of several biologically relevant molecules and zwitterions in water

    NASA Astrophysics Data System (ADS)

    Patuwo, Michael Y.; Bettens, Ryan P. A.

    2012-02-01

    In this work, we study the hydration free energies of butane, zwitterionic alanine, valine, serine, threonine, and asparagine, and two neuraminidase inhibitors by means of Monte Carlo (MC) simulation. The solute molecule, represented in the form of distributed multipoles and modified 6-12 potential, was varied from a non-interacting 'ghost' molecule to its full potential functions in TIP4P water. Intermediate systems with soft-core solute-solvent interaction potentials are simulated separately and then subjected to Bennett's Acceptance ratio (BAR) for the free energy calculation. Hydration shells surrounding the solute particles were used to assess the quality of potential functions.

  6. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    USGS Publications Warehouse

    Schultz, M.M.; Painter, M.M.; Bartell, S.E.; Logue, A.; Furlong, E.T.; Werner, S.L.; Schoenfuss, H.L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305. ng/L and 1104. ng/L) and SER (5.2. ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28. ng/L induced vitellogenin in male fish-a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies. ?? 2011 Elsevier B.V.

  7. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    USGS Publications Warehouse

    Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

  8. On the abundances of noble and biologically relevant gases in Lake Vostok, Antarctica.

    PubMed

    Mousis, Olivier; Lakhlifi, Azzedine; Picaud, Sylvain; Pasek, Matthew; Chassefière, Eric

    2013-04-01

    Motivated by the possibility of comparing theoretical predictions of Lake Vostok's composition with future in situ measurements, we investigated the composition of clathrates that are expected to form in this environment from the air supplied to the lake by melting ice. To establish the best possible correlation between the lake water composition and that of air clathrates formed in situ, we used a statistical thermodynamic model based on the description of the guest-clathrate interaction by a spherically averaged Kihara potential with a nominal set of potential parameters. We determined the fugacities of the different volatiles present in the lake by defining a "pseudo" pure substance dissolved in water owning the average properties of the mixture and by using the Redlich-Kwong equation of state to mimic its thermodynamic behavior. Irrespective of the clathrate structure considered in our model, we found that xenon and krypton are strongly impoverished in the lake water (a ratio in the 0.04-0.1 range for xenon and a ratio in the ≈ 0.15-0.3 range for krypton) compared to their atmospheric abundances. Argon and methane were also found to be depleted in the Lake Vostok water by factors in the 0.5-0.95 and 0.3-0.5 ranges, respectively, compared to their atmospheric abundances. On the other hand, the carbon dioxide abundance was found to be substantially enriched in the lake water compared to its atmospheric abundance (by a factor in the 1.6-5 range at 200 residence times). The comparison of our predictions of the CO2 and CH4 mole fractions in Lake Vostok with future in situ measurements will allow disentangling between the possible supply sources. PMID:23758192

  9. Ki-67 Membranous Staining: Biologically Relevant or an Artifact of Multiplexed Immunofluorescent Staining.

    PubMed

    Wang, Dan; Pang, Zhengyu; Clarke, Gina M; Nofech-Mozes, Sharon; Liu, Kela; Cheung, Alison M Y; Filkins, Robert J; Yaffe, Martin J

    2016-07-01

    In the process of developing a multiplex of 8 common breast cancer biomarkers (Her2/neu, estrogen receptor, progesterone receptor, Ki-67, aldehyde dehydrogenase-1, NaK-ATPase, cytokeratin 8/18, and myosin smooth muscle) on a single formalin-fixed paraffin-embedded slide using a sequential staining, imaging, and dye bleaching technology developed by General Electric Company, membranous Ki-67 staining was observed and colocalized with Her2/neu staining. Using immunohistochemistry as gold standards, we discovered that membranous Ki-67 was an artifact caused by the binding of cyanine 5-conjugated rabbit polyclonal Ki-67 antibody to a secondary cyanine 3-conjugated donkey anti-rabbit antibody which was previously applied and bound to rabbit Her2/neu antibody in our multiplexing experiment. After blocking with rabbit serum, a successful protocol for 8 biomarker multiplexing without cross-reactivity of antibodies from the same species was developed. PMID:26258752

  10. Biochemical features, molecular biology and clinical relevance of the human 15-domain serine proteinase inhibitor LEKTI.

    PubMed

    Walden, Michael; Kreutzmann, Peter; Drögemüller, Katrin; John, Harald; Forssmann, Wolf-Georg; Hans-Jürgen, Mägert

    2002-01-01

    Based on the isolation of a 55 amino acid peptide from human hemofiltrate, we cloned the cDNA for a novel human 15-domain serine proteinase inhibitor termed LEKTI. A trypsin-inhibiting activity was demonstrated for three different domains. High levels of expression of the corresponding gene were detected in oral mucosa, followed by the tonsils, parathyroid glands, thymus, and trachea. Hovnanian and coworkers recently found that certain mutations within the LEKTI gene are linked to the severe congenital disease Netherton syndrome and atopic manifestations (including asthma). Thus, a future therapeutic use of LEKTI is conceivable. PMID:12437098

  11. BIOLOGICAL EFFECTS OF OIL FLY ASH AND RELEVANCE TO AMBIENT AIR PARTICULATE MATTER

    EPA Science Inventory

    Epidemiologic studies have demonstrated increased human morbidity and mortality with elevations in the concentration of ambient air particulate matter (PM). Fugitive fly ash from the combustion of oil and residual fuel oil significantly contributes to the ambient air particle bur...

  12. Interaction Between Titanium Implant Surfaces and Hydrogen Peroxide in Biologically Relevant Environments

    SciTech Connect

    Muyco, J; Ratto, T

    2004-04-21

    Titanium was exposed to dilute solutions of hydrogen peroxide (H2O2) to better characterize the interaction at the interface between the solution and metal. The intensity of light passing through films of known thickness of titanium on quartz was measured as a function of time in contact with H{sub 2}O{sub 2} in concentrations of 0.3% and 1.0%. An atomic force microscope (AFM) was used to record deflection-distance (force) curves as a probe approached the interface of titanium in contact with solution containing 0.3% of H{sub 2}O{sub 2}. The interaction layer measured using AFM techniques was much greater than the thickness of the titanium films used in this study. Raman spectroscopy taken during interaction shows the emergence of a Ti-peroxy gel and titania after 2 hours in contact with 0.3% H2O2 solution.

  13. The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance.

    PubMed

    Zucca, Emanuele; Bertoni, Francesco

    2016-04-28

    Extranodal marginal zone (MZ) B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The best evidence of an etiopathogenetic link is provided by the association between Helicobacter pylori-positive gastritis and gastric MALT lymphoma. Indeed, successful eradication of this microorganism with antibiotics can be followed by gastric MALT lymphoma regression in most cases. Other microbial agents have been implicated in the pathogenesis of MZ lymphoma arising at different sites. Apart from gastric MALT lymphoma, antibiotic therapies have been adequately tested only in ocular adnexal MALT lymphomas where upfront doxycycline may be a reasonable and effective initial treatment of patients with Chlamydophila psittaci-positive lymphoma before considering more aggressive strategies. In all other instances, antibiotic treatment of nongastric lymphomas remains investigational. Indeed, there is no clear consensus for the treatment of patients with gastric MALT lymphoma requiring further treatment beyond H pylori eradication or with extensive disease. Both radiotherapy and systemic treatments with chemotherapy and anti-CD20 antibodies are efficacious and thus the experience of individual centers and each patient's preferences in terms of adverse effects are important parameters in the decision process. PMID:26989205

  14. High content pharmacophores from molecular fields: a biologically relevant method for comparing and understanding ligands.

    PubMed

    Cheeseright, Timothy J; Mackey, Mark D; Scoffin, Robert A

    2011-09-01

    The question of how and why a small molecule binds to a protein is central to ligand-based drug discovery. The traditional way of approaching these questions is pharmacophore analysis. However, pharmacophores as usually applied lack quantitation and subtlety. An improvement is to consider the electrostatic and steric fields of the ligand directly. Molecular fields provide a rich view of the potential interactions that a molecule can make and can be validated through experimental data on molecular interactions and through quantum mechanics calculations. A technique is presented in this review for comparing molecules using molecular fields and assigning similarity scores. This high information content method can be used to align molecules for SAR analysis, to determine the bioactive conformation from ligand data, and to screen large libraries of compounds for structurally unrelated actives. An extension to allow interactive exploration of chemistry space via bioisostere analysis is also reviewed. Examples from the literature showing the success of these methods are presented, and future directions discussed. PMID:21726191

  15. Biological Relevance of Colony Morphology and Phenotypic Switching by Burkholderia pseudomallei▿

    PubMed Central

    Chantratita, Narisara; Wuthiekanun, Vanaporn; Boonbumrung, Khaemaporn; Tiyawisutsri, Rachaneeporn; Vesaratchavest, Mongkol; Limmathurotsakul, Direk; Chierakul, Wirongrong; Wongratanacheewin, Surasakdi; Pukritiyakamee, Sasithorn; White, Nicholas J.; Day, Nicholas P. J.; Peacock, Sharon J.

    2007-01-01

    Melioidosis is a notoriously protracted illness and is difficult to cure. We hypothesize that the causative organism, Burkholderia pseudomallei, undergoes a process of adaptation involving altered expression of surface determinants which facilitates persistence in vivo and that this is reflected by changes in colony morphology. A colony morphotyping scheme and typing algorithm were developed using clinical B. pseudomallei isolates. Morphotypes were divided into seven types (denoted I to VII). Type I gave rise to other morphotypes (most commonly type II or III) by a process of switching in response to environmental stress, including starvation, iron limitation, and growth at 42°C. Switching was associated with complex shifts in phenotype, one of which (type I to type II) was associated with a marked increase in production of factors putatively associated with in vivo concealment. Isogenic types II and III, derived from type I, were examined using several experimental models. Switching between isogenic morphotypes occurred in a mouse model, where type II appeared to become adapted for persistence in a low-virulence state. Isogenic type II demonstrated a significant increase in intracellular replication fitness compared with parental type I after uptake by epithelial cells in vitro. Isogenic type III demonstrated a higher replication fitness following uptake by macrophages in vitro, which was associated with a switch to type II. Mixed B. pseudomallei morphologies were common in individual clinical specimens and were significantly more frequent in samples of blood, pus, and respiratory secretions than in urine and surface swabs. These findings have major implications for therapeutics and vaccine development. PMID:17114252

  16. Supramolecular interactions in biologically relevant compounds. 2-Pyrazineformamide thiosemicarbazones and some products of their cyclization

    NASA Astrophysics Data System (ADS)

    Castiñeiras, Alfonso; García-Santos, Isabel; Nogueiras, Silvia; Rodríguez-González, Iria; Rodríguez-Riobó, Raúl

    2014-09-01

    Reaction of 2-cyanopyrazine with thiosemicarbazide or N-methylthiosemicarbazide afforded the (Z)-2-(amino(pyrazin-2-yl)methylene)hydrazinecarbothioamide (HPzAm4DH) and (Z)-2-(amino(pyrazin-2-yl)methylene)-N-methylhydrazine carbothioamide (HPzAm4M), respectively. (2Z,N‧E)-N‧-(4-Oxothiazolidin-2-ylidene)pyrazine-2-carbohydrazonamide (HPzAmot, 5) and (2Z,N‧E)-N‧-(3-methyl-4-oxothiazolidin-2-ylidene)pyrazine-2-carbohydrazonamide (MPzAmot, 7) have been synthesized from these thiosemicarbazones with chloroacetic or bromoacetic acids, using a conventional synthetic methodology and microwave-assisted organic reaction enhancement. The crystal structures of the thiosemicarbazones and their solvates [HPzAm4DHṡ1/2 MeOH (1), HPzAm4DHṡH2O (2), HPzAm4M (3), HPzAm4Mṡ2H2O (4)] and the 1,3-thiazolidin-4-ones (5 and 7) have been studied by X-ray diffractometry. All of the compounds were characterized by elemental analysis, mass spectrometry, FT-IR and 1H and 13C NMR spectroscopy. Several by-products have also been isolated in a crystalline form, namely 3-((Z,E)-N‧-(4-oxothiazolidin-2-ylidene)carbamohydrazonium-yl)pyrazin-1-ium dibromide monohydrate, (H3PzAmot)Br2ṡH2O (6), 2-((5-(pyrazin-2-yl)-1H-1,2,4-triazol-3-yl)thio)acetic acid, (H2Pz124ttAc) (8), 2-amino-5-(pyrazin-2-yl)-1,3,4-thiadiazol-3-ium chloride monohydrate, (HPz134tda)ClṡH2O (9), and 2-(methylamino)-5-(pyrazin-2-yl)-1,3,4-thiadiazol-3-ium chloride N-methyl-5-(pyrazin-2-yl)-1,3,4-thiadiazol-2-amine solvate, (HMPz134tda)Clṡ(MPz134tda) (10). The structures of these compounds were also analyzed by X-ray diffractometry. The microwave-assisted organic reaction method for synthesis is easy, convenient, and ecofriendly when compared to the traditional synthetic methods. Crystal analysis revealed that the compounds have extended 3D supramolecular networks through high levels of H-bonding and weak molecular interactions between the molecular moieties and solvent molecules. The novel synthons, which are sustained by Nsbnd H⋯N and Nsbnd H⋯O hydrogen bonding and other weak interactions, have been shown to assemble with 1,3-thizolidine-4-ones, 1,2,4-trizole, or 1,3,4-thiadiazole derivatives in a zigzag or herringbone architecture.

  17. Multifrequency Pulsed EPR Studies of Biologically Relevant Manganese(II) Complexes

    PubMed Central

    Stich, T. A.; Lahiri, S.; Yeagle, G.; Dicus, M.; Brynda, M.; Gunn, A.; Aznar, C.; DeRose, V. J.; Britt, R. D.

    2011-01-01

    Electron paramagnetic resonance studies at multiple frequencies (MF EPR) can provide detailed electronic structure descriptions of unpaired electrons in organic radicals, inorganic complexes, and metalloenzymes. Analysis of these properties aids in the assignment of the chemical environment surrounding the paramagnet and provides mechanistic insight into the chemical reactions in which these systems take part. Herein, we present results from pulsed EPR studies performed at three different frequencies (9, 31, and 130 GHz) on [Mn(II)(H2O)6]2+, Mn(II) adducts with the nucleotides ATP and GMP, and the Mn(II)-bound form of the hammerhead ribozyme (MnHH). Through line shape analysis and interpretation of the zero-field splitting values derived from successful simulations of the corresponding continuous-wave and field-swept echo-detected spectra, these data are used to exemplify the ability of the MF EPR approach in distinguishing the nature of the first ligand sphere. A survey of recent results from pulsed EPR, as well as pulsed electron-nuclear double resonance and electron spin echo envelope modulation spectroscopic studies applied to Mn(II)-dependent systems, is also presented. PMID:22190766

  18. Effects of Prostaglandin F2α on Adipocyte Biology Relevant to Graves' Orbitopathy

    PubMed Central

    Draman, Mohd Shazli; Grennan-Jones, Fiona; Zhang, Lei; Taylor, Peter N; Tun, Tommy Kyaw; McDermott, John; Moriarty, Paul; Morris, Daniel; Lane, Carol; Sreenan, Seamus; Dayan, Colin

    2013-01-01

    Background: In Graves' orbitopathy (GO), increased proliferation, excess adipogenesis, and hyaluronan overproduction produce GO exophthalmos. Enophthalmos occurs in some glaucoma patients treated with Bimatoprost (prostaglandin F2α, PGF2α) eye drops. We hypothesized that enophthalmos is secondary to reductions in orbital tissue proliferation, adipogenesis, and/or increased lipolysis. We aimed to determine which of these is affected by PGF2α by using the 3T3-L1 murine preadipocyte cell line and primary human orbital fibroblasts (OFs) from GO patients (n=5) and non-GO (n=5). Methods: 3T3-L1 cells and orbital OFs were cultured alone or with PGF2α (all experiments used 10−8 to 10−6 M) and counted on days 1/2/3 or 5, respectively; cell cycle analysis (flow cytometry) was applied. Adipogenesis (in the presence/absence of PGF2α) was evaluated (day 7 or 15 for 3T3-L1 and primary cells, respectively) morphologically by Oil Red O staining and quantitative polymerase chain reaction measurement of adipogenesis markers (glycerol-3-phosphate dehydrogenase and lipoprotein lipase, respectively). For lipolysis, in vitro–differentiated 3T3-L1 or mature orbital adipocytes were incubated with norepinephrine and PGF2α and free glycerol was assayed. Appropriate statistical tests were applied. Results: The population doubling time of 3T3-L1 was 27.3±1.4 hours—significantly increased by dimethyl sulfoxide 0.02% to 44.6±4.8 hours (p=0.007) and further significantly increased (p=0.049 compared with dimethyl sulfoxide) by 10−8 M PGF2α to 93.6±19.0 hours, indicating reduced proliferation, which was caused by prolongation of G2/M. GO OFs proliferated significantly more rapidly than non-GO (population doubling time 5.36±0.34 or 6.63±0.35 days, respectively, p=0.035), but the proliferation of both was significantly reduced (dose dependent from 10−8 M) by PGF2α, again with prolongation of G2/M. Adipogenesis in 3T3-L1 cells was minimally affected by PGF2α when assessed morphologically, but the drug significantly reduced transcripts of the glycerol-3-phosphate dehydrogenase differentiation marker. GO OFs displayed significantly higher adipogenic potential than non-GO, but in both populations, adipogenesis, evaluated by all 3 methods, was significantly reduced (dose dependent from 10−8 M) by PGF2α. There was no effect of PGF2α on basal or norepinephrine-induced lipolysis, in 3T3-L1 or human OFs, either GO or non-GO. Conclusions: The results demonstrate that PGF2α significantly reduces proliferation and adipogenesis and that human OFs are more sensitive to its effects than 3T3-L1. Consequently, PGF2α could be effective in the treatment of GO. PMID:24001049

  19. COMPREHENSIVE ANALYSIS OF BIOLOGICALLY RELEVANT ARSENICALS BY PH-SELECTIVE HYDRIDE GENERATION-ATOMIC ABSORPTION SPECTROMETRY

    EPA Science Inventory


    A method based on pH-selective generation and separation of arsines is commonly used for analysis of inorganic, methylated, and dimethylated trivalent and pentavalent arsenicals by hydride generation-atomic absorption spectrometry (HG-AAS). We have optimized this method to pe...

  20. Lake Shore and Littoral Habitat Structure: Precision and biological Relevance of a Field Survey Method.

    EPA Science Inventory

    Until recently, lake physical habitat assessment has been an underemployed tool for assessing lake and reservoir ecological condition. We outline and evaluate a rapid field sampling and analytical approach for quantifying near-shore physical habitat. We quantified the repeatabil...